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MANUAL 


PATHOLOGY 


INCLUDING    BACTERIOLOGY,    THE    TECHNIC   OH 

POSTMORTEMS,    AND    METHODS    OF 

PATHOLOGIC    RESEARCH 


W.    M.     LATE    COPLIX,    M.D. 

PROFESSOR   OF    PATHOLOGY    ANU   BACTERIOLOC.Y,   JKFFKRSON    MEDICAL   COLLEGE.  PHILADELPHIA  :    PATHOWHJIST 

TO   JEFFERSON    MEDICAL   COLLEGE    HOSPITAL    AND  TO   THE   PHILADELPHIA  (BLOCKLEV,    HOSPITAL; 

DIRECTOR     OP    THE    CLINICAL    LABORATORIES    OP   THE    JEFFERSON     MEDICAL 

COLLEGE    hospital;    PATHOLOGIST   TO   THE    FRIENDS* 

ASYLUM  FOR  THE  INSANE,  PRANKFOKD 


FOURTH  EDITION,  REWRITTEN  AND  ENLARGED 


lUitb    Jfour   1bun&rcC»   anD   Winctv^fivc   lllliunrntioni 

.WANV  OF-   VVHK.H   Akl.   OkK.INAl.. 

a  n  D    Zen    Colored    |M  a  t  c  ^^ 


IIA 

P.    BLAKISTON'S    SON    &    CO. 

IOI2     WALNLT     STREET 


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^'■rr: 


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Copyright,  1905,  by  P.  Bi.akiston's  Son  &  Co. 


WM.   F.   FELL    COMPA^Y 

ElECTROTYPERS    AND    PRINTERS 

1220-24    SANSOM    STREET 

PHILADELPHIA,  PA. 


TO 

W.  W.  KEEN,  M.D. 

PROFESSOR    OF    THE    PRINCIPLES    OF    SURCERV    AND    CLINICAL    SCRCERV 

IN    THE   JEFFERSON    MEDICAL    COLLEGE, 

AS    A    TOKEN    OF    RESPECT    AND    GRATITUDE    THIS 

VOLUME    IS    DEDICATED 

BY 

THE  AUTHOR. 


PREFACE  TO  SECOND  EDITION 


During  the  winter  of  1894  and  1895,  Messrs.  P.  Blakiston.  Son  &  Co. 
published,   in   serial   form,   abstracts  of   the   writer's   lectures,   entitled 
"Lectures  on  Pathology."     At  the  close  of  the  college  session  the  fasci- 
culi were  bound,  and  the  resulting  volume  placed  on  the  market.     Very- 
much  to  the  surprise  of  the  publishers,  as  well  as  of  the  writer,  the  edition 
lasted  less  than  nine  months.     It  was  exhausted  at  a  time  when  the 
teaching  of  the  college  year  precluded  the  revision  which  the  matter  so 
much  needed.     During  the  past  six  months  the  entire  book  has  been  re- 
vised, the  larger  part  having  b^en  entirely  rewritten.     The  first  edition 
contained  250  pages  and  51  illustrations;    the  present  volume,  in  the 
face  of  every  effort  to  condense  without  sacrificing  accuracy,  has  reached 
638  pages  and  contains  268  illustrations.     The  most  difficult  probl.m 
has  been  to  keep  the  volume  from  assuming  undesired  dimensions.  : 
now  that  the  work  is  completed,  the  writer  wishes  to  say,  parent  li 
cally,  that  a  volume  of  twice  the  size  could  have  been  produced  v 
probably  less  labor.     Being  practically  a  new  book,  there  are,  no  doi 
typographic  and  grammatic  errors.     The  writer  acknowledges  in  ad\-.. 
his  appreciation  of  any  communication  calling  his   attt-Titioii   to   s 

lapses. 

In  the  publication  of  the  original  fasciculi  the  writer  w.is  1.. 
the  aid  of  Professor  Kyle  and  Dr.  Bevan.     Professor  Kyle  v  n 

fasciculus  on  "Tumors,"  and  Dr.  Bevan  the  article  on  "Bacteriology." 
In  the  revision  of  the  work  both  articles  have  been  somewhat 
but  the  thoroughness  of  the  original  has  not  demanded  any 
revision.     There  have  been  made  some  additions  and  a  rearrangement 
of  subjects,  in  order  to  secure  greater  conformity        "     "      remamder  ot 
the  book.     In  the  original,  acknowledgment  of  th.  '•  was  given 

with  the  fasciculi;    it  is  now  incorporated  here. 

Practicallv.  all  the  added  illustrations  appear  lur  itic  nrst  time  in  a 
work  on  pathologv  in  the  English  language.  The  source  is  credited 
with  each  cut.  Of  the  original  illustrations  it  is  not  the  author's  prov- 
ince to  speak.  Thev  have  been  prepared  in  the  writer's  laboratory  from 
specimens  and  slides  of  which  the  clinical  and  pathologic  histoloi^y  were 
fullv  known.  In  this  connection  the  writer  wishes  to  acknowledge  the 
invaluable  assistance  of  Professor  H.  F.  Harris,  who  personally  super- 

xi 


Xll  PREFACE    TO    SECOND    EDITION. 

intended  the  execution  of  most  of  the  original  drawings.  Miss  E.  G. 
Harding,  artist,  has,  with  great  patience,  made  the  original  drawings, 
often  redrawing  an  illustration  a  number  of  times  before  submitting  it 
for  approval. 

In  conclusion,  the  writer  wishes  to  submit  the  volume,  not  as 
a  treatise  or  book  of  reference,  but,  as  its  title  indicates,  as  a  manual 
that  he  hopes  may  be  useful  in  the  laboratory,  postmortem  room,  and 
in  clinical  diagnosis  by  the  aid  of  the  microscope.  To  attain  as  fully 
as  possible  the  last-named  aim,  the  chapters  on  the  microscopic  exami- 
nation of  tissues,  blood,  and  urine  have  been  most  fully  illustrated. 

Thanking  the  profession  for  its  kindly  reception  of  the  previous 
edition,  this  volum.e  is  respectfully  submitted  for  consideration. 


PREFACE  TO  FOi;Kril  HDH10N. 


In  presenting  to  the  profession  and  students  of  medicine  the  fourth 
edition  of  this  work  I  wish  gratefully  to  acknowledge  the  cordial  recep- 
tion accorded  the  third  edition.  Although  much  larger  than  any  pre- 
ceding revision,  and  twice  reprinted,  the  book  practically  has  been  out 
of  print  for  over  one  year.  During  that  time  I  have  occupied  my  spare 
moments  in  revising,  rewriting,  and  rearranging  the  subject-matter.  A 
number  of  the  old  illustrations  have  been  replaced  by  new.  and  many 
original  drawings  have  been  added. 

My  conviction  that  properly  prepared  figures  are  of  the  utmost  im- 
portance in  elucidating  the  subject  under  consideration  remains  un- 
changed; in  accord  with  this  view  the  number  of  illustrations  has  been 
increased  from  three  hundred  and  thirty,  to  four  hundred  and  ninety- 
five;  practically  all  those  added  are  original.  The  colored  plates,  which 
first  appeared  in  the  last  edition,  have  been  continued  and  the  number 
increased  by  the  addition  of  others  illustrating  the  parasitology  of 
malaria,  and  the  blood-changes  of  leukemia.  For  both  sets  of  addi- 
tional plates— five  in  all — I  am  indebted  to  Dr.  John  C.  Da  Costa.  Jr.. 
who  kindly  placed  at  my  disposal  the  superb  illustrations  from  his  br.ok 
on  "Clinical  Hematology." 

The  chapter  on  postmortem  examinations  has  been  ri\is<(i  an-i 
enlarged,  and  new  methods  have  been  introduced  in  the  chapters  on 
technic.  Bacteriologic  technic  has  been  transferred  to  the  Appendix, 
in  which  are  also  included  brief  practical  summaries  of  the  methods  of 
microscopic  examination  of  the  urine,  and  also  the  sputum.  The  tech- 
nic of  blood  examination  is  fully  but  briefly  reviewed  in  the  chapter  on 
blood,  with  which  it  properly  belongs.  Special  technic  has  been  dis- 
tributed throughout  the  book ;  whenever  it  was  necessary  to  adopt  any 
specific  means  for  demonstrating  a  reaction  or  for  satisfactorily  staining 
morbid  products,  the  method  has  been  given  with  the  consideration  of 
the  materials  to  be  treated.  The  chapters  on  immunity  and  on  the 
pathology  of  infections  have  been  entirely  rewritten  and  more  fully  illus- 
trated. The  relation  of  poisons  to  disease  production  is  discussed  with 
some  detail,  and  the  recent  theories  of  intoxication,  and  cytolytic  pro- 
cesses, bearing  on  problems  in  general  pathology,  have  been  deemed 
important  and  worthy  of  incorporation.     A  chapter  on  malt^"^^"    '"^ 

vii 


vni  PREFACE    TO    FOURTH    EDITION. 

including  teratogenesis,  has  been  added.  The  new  matter  has  increased 
the  text  by  about  one-third,  but,  by  enlarging  the  size  and  diminishing 
the  margins  of  the  page,  and  by  other  expedients  well  known  to  the 
experienced  publisher,  it  has  been  possible  to  secure  a  less  bulky  and, 
I  believe,  a  more  presentable  volume. 

Extended  experience  has  led  to  the  belief  that  many  readers  desire 
more  information  than  the  scope  of  this  work  permits,  and  that  often 
an  inquirer  after  the  truth  wishes  to  study  the  literature  of  some  sub- 
ject, too  briefly  considered  in  a  text-book  or  manual.  To  meet  this 
demand  I  have  inserted,  in  the  present  edition,  numerous  references  to 
original  articles,  usually  selecting  those  papers  to  which  a  fuller  biblio- 
graphy is  appended.  In  no  case  are  the  references  complete,  or  even 
exhaustive,  but  practically  all  are  to  recent  communications;  few  only 
are  to  publications  antedating  the  year  1900.  Wherever  possible  I  have 
given  references  to  an  article  in  German,  another  in  French,  and  still 
another  in  English;  occasionally  acceptable  articles  in  other  languages 
are  mentioned.  As  the  literature  available  for  most  practitioners  and 
students  is  largely  in  English,  many  of  the  references  are  to  publications 
in  that  language. 

The  chapter  on  diseases  of  the  nervous  system,  originally  written 
by  Prof.  H.  F.  Harris,  has  been  fully  revised  and  contains  considerable 
new  matter.  Dr.  Alfred  Gordon,  Instructor  in  Neuropathology  in  the 
Jefferson  Medical  College,  has  kindly  loaned  me  a  number  of  exception- 
ally good  illustrations  and  made  valuable  suggestions  in  completing  the 
revision  of  this  part  of  the  work. 

The  labor  incident  to  revision  has  been  lessened — indeed  revision 
at  this  time  was  rendered  possible — by  the  cooperation  and  cordial  assis- 
tance of  a  corps  of  fellow-workers  who  generously  gave  time  and  effort, 
particularly  by  relieving  me  of  the  onerous  duties  incident  to  supervision 
of  a  busy  Clinical  Laboratory.  To  these  gentlemen — Dr.  AUer  G.  Ellis 
and  Dr.  John  Funke — I  wish  to  make  a  most  grateful  acknowledgment 
of  my  indebtedness.  Dr.  Ellis  revised  the  chapter  on  the  blood.  I  am 
also  under  obligation  to  Dr.  Randle  C.  Rosenberger  for  aid  in  the  com- 
pilation of  stain  reactions  and  biologic  peculiarities  of  the  bacteria. 
Dr.  Frederick  J.  Kalteyer  has  aided  by  kindly  loaning  specimens  for 
illustrations.  The  table  on  the  blood  occupying  pages  428  and  429  is 
largely  the  product  of  his  energy.  Mr.  Clark  Evans  has  prepared  the 
index. 

Many  of  the  new  drawings  are  by  Miss  S.  L.  Clark,  whose  skill  is  at- 
tested by  the  results  attained.  The  reproduction  of  the  new  illustra- 
tions, both  colored  and  uncolored,  has  been  trusted  entirely  to  the  pub- 
lishers, to  whom  the  author  is  under  many  obligations  for  the  careful 
execution  of  this  most  difficult  task,  and  for  other  courtesies. 


PRKIACE    TO     KOURTII     KDITlO.V. 

In  conclusion  the  author  wishes  to  state  that  tlie  oigiM  t  i,\  im-  im^.k 
has  not  been  changed,  and  that  the  present  echtion,  although  greatly 
enlarged,  remains  exactly  what  the  author  intended  the  previous  editions 
to  be:  namely,  "not  a  treatise  or  book  of  reference,  but,  as  its  title 
indicates,  a  manual  that  the  author  hopes  may  be  useful  in  the  labora- 
tory and  postmortem  room  and  in  clinical  diagnosis  by  the  aid  of  the 
microscope. " 

\V.  M.  L.  C. 


TABLE  OF  CONTENTS. 


PART  I.     TECHNIC. 

CIIAl'TER  1. 

PACE 

Postmortem   Examinations 1-32 

Description  of  Instruments  Needed. — Arrangement  of  Postmortem 
Room. — Records  of  Postmortems. — External  Examination  of 
the  Body. — Internal  Examination  of  the  Body. — Letulle's 
Method. — Bacteriologic  Examination  of  Organs. — Restoration 
of  the  Body. — Preservation  of  Tissues. 

CHAPTER  II. 

Histologic  Methods 33~52 

Fixation  of  Tissues  and  Fixing  Agents. — Infiltration  Methods  and 
Section  Cutting. — Staining  and  Mounting  Sections. — The  Micro- 
scope and  Method  of  Using  the  Instrument. 


PART  II.— GENERAL  PATHOLOGY. 

Introdvction 55-57 

CHAPTER  I. 

Abnormal.     Malposition.     Malformatio.v 58-63 

The  Normal. — Abnormal. — Malpositions. — Malformations. — Terato- 
genesis. — Types  of  Malformations. 

CHAPTER  II. 

Disease, 64-80 

Organic  Diseases. — Functional  Diseases. — Nosology. — Acute  Dis- 
ease.— Chronic  Disease. — Pathogenesis. — Internal  Causes. — Sex. 
— Race. — Idiosyncrasy. -7— Heredity. — External  Causes. — Occu- 
pation.— Habits. — Starvation  and  Allied  Conditions. — Ther- 
mal Causes. — Trauma. — Alterations  in  Atmospheric  Pressure. — 
Electric  Discharges. — Poisons  and  their  Classification. — Exo- 
genous   Poisons. — Endogenous    Poisons. 

CHAPTER  III. 

Bacteria  as  Causes  of  Disease .'*i   <> ; 

General  Considerations. — Reproduction  of  Bacteria. — Bacterial  Pro- 
ducts.— Toxins. — Infection. — Subinfection. — Paths  of  Infec- 
tion.— Paths  of  Extension. 

CHAPTER  IV. 

Bacteria  as  Causes  of  Disease  {Continued).     Immunity 94-»oS 

Forms  of  Immunity. — Natural  Immunity. — Acquired  Immunity. — 
Passive  Immunity. — Local  Immunity.— .Antitoxic  Immunity. — 
Bacteriol\-tic  Immunity. — Theories  of  Immunity. — Phagocyto- 
sis.— Opsonins. — Cellulohumeral  Theory. — .Ehrlich's  Side-chain 
Theory. — Agglutinins. — Precipitins. 

xiii 


XIV  TABLE    OF    CONTENTS. 

PAGE 

CHAPTER  V. 

Bacteria  as  Causes  of  Disease  {Concluded).     The  Pathology  of  In- 
fections,     106-1S0 

Diseases  due  to  Micrococci. — Diseases  due  to  Bacilli. — Diseases  due 
to  Spirilla. — Diseases  due  to  Spirochaetse. 

CHAPTER  VI. 

Animal  Parasites  as  Causes  of  Disease, 181-214 

Diseases  due  to  Protozoa. — Diseases  due  to  Vermes. — Diseases  due 
to  Arthropoda. 

CHAPTER  VII. 

Hypertrophy.     Hyperplasia.     Metaplasia.     Heteroplasia.     Hypo- 
plasia.— Agenesis  or  Aplasia 215-223 

CHAPTER  VIII. 

Infiltrations  and  Degenerations 224-248 

Fatty  Infiltration. — Amyloid  Infiltration. — Pigmentary  Infiltration. 
- — Calcareous  Infiltration. — Glycogen  Infiltration. — Parenchy- 
matous Degeneration. — Fatty  Degeneration. — Hydropic  De- 
generation.— Colloid  Degeneration. — Myxomatous  Degenera- 
tion.— Hyaline  Degeneration. — Corneous  Degeneration. 

CHAPTER  IX. 

Necrosis, 249-258 

Liquefaction  Necrosis. — Coagulation  Necrosis. — Fat  Necrosis. — 
Caseation. — Gangrene. 

CHAPTER  X. 

Circulatory  Disturbances 259-284 

Anemia. — Hyperemia. — Hemorrhage. — Hemophilia.  —  Lymphorrha- 
gia. — Congestion. — Stasis.- — Edema. — Thrombosis.- — Embolism. 
— Infarction. 

CHAPTER  XI. 

Inflammation  and  Repair, 285-307 

CHAPTER  XII. 

Tumors, 308-371 

Neoplasms. — Cysts. — Teratomata. 

CHAPTER  XIII. 

Temperature  Changes.     Fever 372-381 

Hypothermia. — Pyrexia. — Intoxications. — Local  Infections. — Bac- 
teremia. 


PART  III.— SPECIAL  PATHOLOGY. 

CHAPTER  I. 

Blood,.... 385-430 

Technic.^ — -General  Pathology,  Composition  and  Structure  of  the 
Blood. — Anemias. — Chlorosis.- — Pernicious  Anemia. — Leukemia. 
— Pseudoleukemia. — Splenic  Anemia. — Mycoses  of  the  Blood. — 
Animal  Parasites  of  the  Blood. 


TABLE    OF    CONTENTS.  XV 

CHAPTER  II.  '*"' 


Spleen. 


CliAl'TER  III 


Lymph-nodes, 


431-441 


442-449 


CHAPTER   IV. 
Thymis   Body .    450-451 

CHAPTER  V. 
Serous  Membranes 452-481 

CHAPTER  VI. 

Vascular  System .  .   482-539 

Heart. — Arteries. — Veins. — Lymph-vessels. 

CHAPTER  VII. 
Mucous  Me.mbraxes 540-563 

CHAPTER  VIII. 

Organs  of  Respiration 564-627 

Nose. — Larynx  and  Trachea. — Bronchi. — Lungs. 

CHAPTER  IX. 

Diseases  of  the  Urinary  Organs .  .    62S-672 

Kidney. — Bladder.— Crethra. 

CHAPTER  X. 

Alimentary'  Canal 673-736 

Mouth. — Tonsils. — Pharynx. — Salivary  Glands. — Esophagus. — 
Stomach. — Intestines. 

CHAPTER  XI. 
Liver  and  Biliary  Passages, .    737-766 

CHAPTER  XII. 
Pancreas .    767-774 

CHAPTER  XIII. 

Ductless  Glands •    775-787 

Thyroid  and  Parathyroids. — Suprarenals. 

CHAPTER  XIV. 
Muscles •    "88-797 

CHAPTER  XV. 
Bones  and  Joints ■    798-832 

CHAPTER  XVI. 

Nervous  System •   833-894 

Meninges. — Cord. — Brain. — Peripheral    Nerves. 


XVI  TABLE    OF    CONTEXTS, 

PART  IV  (APPENDIX).— GENERAL  LABORATORY  TECHNIC. 

PAGE 

CHAPTER  I. 
Bacteriologic  Technic, 897-933 

CHAPTER  II. 
Microscopic  Examination  of  Urine, 934-945 

CHAPTER  III. 
Technic  of  Sputum  Examination, 946-948 


Index. 


LIST  OF  ILLUSTRATIONS. 


COLORED    PLATES. 

Plate  pAor 

I.   The  Tertian  Parasite   (Da  Costa) f acinic  i86 

II.  The  Quartan   Parasite   (Da  Costa), facing  i88 

III.  The  Estivo-autuiTinal   Parasite   (Da  Costa) facing  190 

IV.  Cut  Surface  of  Spleen  Showing  Lardaceous  Change,  and  lodin 

Reaction  ("Atlas  of  Pathology,"  Sydenham  Society) facing     230 

V.  Spleno-Medullary  Leukemia  (Da  Costa), facing     424 

VI.   Lymphatic  Leukemia  (Da  Costa) facing     426 

VII.   Lung,     Croupous     Pneumonia.     State    of    Red     Hepatization. 

(Fox's  Atlas.) facing     600 

VIII.   Lung,    Croupous    Pneumonia.     Stage    of    Gray    Hepatization. 

(Moditied  from  Bollinger) facing     604 

IX.  Diseases    of    the    Kidney    ("Atlas    of    Pathology,"    Sydenham 

Society), ' facing     654 

Fig.  I.   Kidney,  Chronic  Interstitial  Nephritis. 
Fig.  II.   Part  of  Kidney,   Subacute   Parenchymatous  Nephritis. 
From  girl,  six  and  a  half  years  old;    scarlet  fever; 
death  on  the  forty-seventh  day.     More  advanced 
degenerative  change  than  in  hgure  IV. 
Fig.  III.   Part  of  Kidney,  Chronic  Parenchymatous  Nephritis. 
Fig.  IV.   Part    of    ;Kidney,    Acute    Parenchymatous    Nei)hritis. 
From  a  boy,  nine  years  old;    scarlet  fever;    death 
on   the   twenty-second   day   of   the   disease.     The 
initial  stage  of  engorgement   is  no  longer  present. 
X.  Tuberculosis  of  Bladder,.  .  .  .facing     670 


Fig.  Pace 

1.  Complete    Postmortem   Case 2 

2.  Modified  Virchow  Postmortem    Knife 0 

3.  Median  Incision,  showing  Method  of  Opening  the  Abdominal  Cavity 

(Letulle), 7 

4.  The  Sternum,  Costal  Cartilages,  and  Articulation  of  the  Clavicle,  as 

Exposed  after  Turning  Back  the  Soft  Parts  (modified  from  Virchow), . .  8 

5.  Costotome 9 

6.  Saw 10 

7.  Heart,  Showing  the  Lines  for  Incisions  in  the  Preliminary  Examination 

and  Final  Section.  Fully  Exposing  the  Valves  (after  Virchow) 11 

8.  Heart  Showing  the   Interior  of  the  Right  Ventricle  and  Pulmonary 

Artery  (after  Virchow  1 12 

9.  Heart  with  the  Left  Ventricle  Laid  Open,  Showing  the  Aortic  Cusps  and 

the  Ventricular  Aspect  of  the  Mitral  Valve  (after  Virchow) 13 

10.  Scissors '4 

1 1 .  Grooved    Director '5 

12.  Line  of  Incision  through  the  Posterior  Border  of  the  Lung  (Letulle) 16 

13.  Incision  fcr  Separating  the  Oral  and  Pharyngeal  Structures  from  the 

Floor  of  the  Mouth  (Letulle) , • ^7 

14.  Long,  Thin,  Brain  Knife,  of  Value  for  Incising  Organs,. 18 

Is.   Entcrotome ^* 


XVIU  LIST    OF    ILLUSTRATIONS. 

Fig.  Page 

i6.  Probes 19 

17.  Dissecting   Forceps, 20 

18.  Mallet  or  Hammer 20 

19.  Heavy  Line  Indicating  Course  Taken  by  Saw-cut  in  So-called  Under- 

taker's Method, 21 

20.  Circumferential  Saw-cut,  to  be  Preferred  in  all  Medico-legal  Cases 22 

21.  Wedge-shaped  Calvaria  Removed  by  the  Line  of  Saw-cut  Recommended,  23 

22.  Chisels, 24 

23.  Myelotome, 24 

24.  Scalpel  with  Blade  Shaped  Somewhat  Like  a  Bistoury, 25 

25.  Double  Saw  for  Sawing  through  the  Laminae  of  Both  Sides  at  Once, 26 

26.  Perineal  Incision  for  Removing  Anus,  Bladder,  etc.,  in  the  Male  (Le- 

tulle) ■  ■  27 

27.  Perineal  Incision  for  Removing  the  Rectum,  Anus,  and  Reproductive 

Organs  of  the  Female  (LetuUe), 28 

28.  Bone-cutting  Forceps, 29 

29.  Postmortem  Needles 3° 

30.  Metallic  Table  for  Fixation  and  Paraflfin  Infiltration, 35 

31.  Block  for  Mounting  Tissue  Infiltrated  with  Paraffin, 36 

32.  Properly  Trimmed  Block, 36 

33.  Method  of  Applying  Paper  to  Block, 36 

34.  Block  Showing  Tissue  in  Position 37 

35.  Mounted  Tissue  Ready  for  Sectioning, 37 

36.  Naple's  Paraffin  Bath  for  Infiltrating  Tissues  in  Paraffin, 38 

37.  Forceps   Convenient    for    Handling   Cover-glasses,  Blocks  of   Tissues, 

and  Sections, 38 

38.  Laboratory  Microtome, 39 

39.  Small  Microscopic  Scissors 39 

40.  Ryder  Microtome, 4° 

41.  Ranvier's  Microtome, 4° 

42.  Minot  Microtome 41 

43.  Drying  Oven, 42 

44.  Needles  and  Brush  Suitable  for  Handling  Sections 43 

45.  Dish  for  Removing  Paraffin  and  Corrosive  Sublimate  and   for  Dehy- 

drating,    44 

46.  Dropping  Bottle  with  Barnes's  Dropper,  which  Closes  the  Mouth  of  the 

Bottle  Like  a  Rubber  Stopper 46 

47.  Proper  Size  Labels  for  Labeling  Microscopic  Slides 46 

48.  Microscope  Suitable  for  General  Pathologic  and  Bacteriologic  Work, ....  51 

49.  Pygopagus   (Debierre,   Simes'  Translation), 62 

50.  Marks  Produced  by  Lightning   (Ziegler), 74 

51.  Propagation  by  Fission   (Coplin  and  Bevan), 82 

52.  From  Culture  of  Bacillus   megatherium 8^ 

53.  Bacillus    butyricus 86 

54.  Bacillus  acidi   lactici 86 

55.  Cells  from  Exiidate,  Case  of    Empyema, 98 

56.  Diagram  Illustrating  Ehrlich's  Views   Concerning   the  Union  between 

Toxin  and  Cell loi 

57.  Diagram  Illustrating  Ehrlich's  Views   Concerning   the  Union  between 

Complement,  Immune  Body,  and  Cell  in  the  Process  of  Cytolysis  In- 
cluding Hemolysis   and   Bacteriolysis, •  •  •  102 

58  and  59.  Diagrams  Illustrating  Ehrlich's  Views  Concerning  the  Action 
of  Anti-immune  Body  and  Anti-complement  in  Preventing  Cytoly- 
sis, Including  Hemolysis  and  Bacteriolysis, 103 

60.  Diagram  Illustrating  the  Nomenclature  of  Schizomycetes  Based  upon 

their  Morphology  (after  Schenck), 107 

6 1 .  Gonococcus, 108 

62.  Diagram  of  the   Diplococcus  of   Pneumonia,    Illustrating   Relation  of 

Capsule  to  the  Contained  Germ   (Coplin  and  Bevan) no 

63.  Sputum,  Croupous  Pneumonia, m 

64.  Micrococcus  (Staphylococcus)  pyogenes  aureus  (Coplin  and  Bevan),    ...  113 

65.  Streptococcus  of  Erysipelas   (Coplin  and  Bevan), iiS 

66.  Margin  of  Membrane  from  Tonsil,  Case  of  Diphtheria 120 

67.  Bacillus^tetani.      Pure  Culture  from^Wound, 121 


LIST    OP    ILLUSTRATIONS.  XIX 

Fig.  Paci: 

68.  Bacillus  anthracis  in  Blood  of  Rabbit 124 

69.  Bacillus  of  Symptomatic  Anthrax  Containing  Spores  (Coplin  and  Bevan)  1 26 

70.  Bacillus  of  Symptomatic  Anthrax  Between  Muscle-fibers  of  Inoculated 

Guinea-pig 127 

71.  Bacillus  of  Influenza 127 

72.  Highly  Magnified  Portion  of  a   Necrotic   Lymph-node  Showing   Pest 

Bacilli 129 

73.  Section   of   Kidney   Showing    Malpighian   Body   Containing    Pest   Ba- 

cilli  s 131 

74.  Bacillus  of  Soft  Chancre 132 

75.  Koch-Weeks  Bacillus  (Hansell  and  Sweet) 133 

76.  Bacillus  lacunatus  (Hansell  and  Sweet) 133 

77.  Bacillus  pyocyaneus, 134 

78.  Bacillus  typhosus 139 

79.  Bacillus  typhosus.     Showing  Flagella  (Gould), 139 

80.  Spirillum  cholera   asiaticae;   Pure  Culture, 143 

81.  Bacillus  tuberculosis, 145 

82.  Bacillus  tuberculosis  (von  Jaksch), 146 

83.  Diagram  of  the  Structure  of  a  Tubercle;    A  Purely  Theoretic  Idea, 

Rarely  Demonstrated   (Gould) J 50 

84.  Acute  Disseminated  Tuberculosis  of  the  Lung  (Schmaus) 151 

85.  Bacillus   leprae    (Extracellular) 158 

86.  Bacillus  of  Rhinoscleroma 159 

87.  Bacillus  mallei.  Pure  Culture 160 

88.  Aspergillus 163 

89.  Favus  from  a  Mouse  (Coplin  and  Bevan) 164 

90.  Microsporon  furfur  (Coplin  and  Bevan) 165 

91.  Oidium  albicans   (Thrush  Fungus)   (Coplin  and   Bevan) 166 

92.  Actinomyces  (Ray  Fungus)  from   Bovine  Actinomj-cosis   (Coplin  and 

Bevan)', 166 

93.  Actinomvces,  from  Culture 167 

94.  Yeast  Cells  from  Pure  Culture,  Budding  Forms  are  Present 171 

95.  Spirochaeta  Obermeieri    (Spirillum   of    Relapsing   Fever)    (Coplin  and 

Bevan) 172 

96.  Spirillum  of  Vincent  and  the  Fusiform  Bacillus;    Other  Organisms  are 

also  Present.      (From  a  case   reported   bv   Dr.  Rosenberger) 173 

97.  Spirochaeta  from  a  Case  of  Syphilis  (McW'eeney), 174 

98.  Trypanosoma  lewisi 183 

99.  Trypanosoma  gambiense  in  Human  Blood 184 

100.  Coccidium  oviforme  from  the  Human  Liver  (after  Leuckart, — Gould),.  185 
loi.   Diagrammatic   Representation  of  the   Life  Cycle  of  the   Plasmodium 

.Malariae  (modified  and  redrawn  after  Clarke), 188 

102.  Fasciola  hepatica • •  I93 

103.  Schistosoma  haematobium,  Male  and  Female,  the  Latter  in  the  Canalis 

Gynaecophorus  of  the  Former  (after  Leuckart, — Gould) 104 

104.  Taenia  saginata    (Gould) 196 

105.  Cephalic  End  of  Taenia  saginata 196 

106.  Head  of  Taenia  solium.     On  the  Right,  Egg  of  Taenia  soHum  (Gould),. . .  197 

107.  Cysticercus  cellulosae.     Completion  of  Head  Formation  (after  Leuckart, 

— Coplin  and  Bevan), 107 

loS.   Hymenolepis    diminuta '9* 

109.  Tc-enia  echinococcus  (after  Leuckart, — CopUn  and    Bevan) 198 

1 10.  Hydatid  Cyst,  showing  Daughter    Cysts i99 

111.  Echinococcus.     A  Group  of  Scolices  (from  Dr.   Loux's  Case) 200 

H2.   Echinococcus.     Scolex  (from   Dr.   Loux's  Case) -joo 

113.  Echinococcus  Hooklets  (from  Dr.   Loux's  Case) 201 

114.  Dibothriocephalus  latus  (after  Leuckart, — Gould) aoi 

115.  Free-swimming  Embryo  of  the  Dibothriocephalus  latus  (after  Leuckart. 

—Gould) ' 201 

116.  Club-shaped  Head  of  the  Dibothriocephalus  latus  (after  Leuckart. — 

Gould) 30I 

117.  Ascaris  lumbricoides  and  Eggs  (Coplin  and  Bevan), 20a 

118.  Oxvuris  vermicularis  (Coplin  and  Bevan) 203 

119.  Male  Tricocephalus,  Trichiurus  or  Whipworm 203 


XX  LIST    OF    ILLUSTRATIONS. 

Fig.  Page 

120.  Trichina  spiralis   (after  Leuckart), 205 

121.  Cephalic    Extremity    of     Uncinaria     Duodenalis    ("Old-world    Hook- 

worm"),  Profile  and  Front  View   (after  Leuckart, — Gould) 205 

122.  Duodenum  showing   Attached  Uncinarite 206 

123.  Filaria  Embryo  (from  F.   P.  Henry's  Case) 207 

124.  Section  of  Head  of  Mosquito  showing  Filaria  in  Position  to  be  Inocu- 

lated during  the  Act  of  Biting   (from  Howard,    after   Manson) 209 

125.  Elephantiasis  of  the  Scrotum 210 

126.  Dracontiasis,  or  Guinea-worm  Disease, 211 

127.  Acarus  scabiei, 212 

128.  Scabies 212 

129.  Pediculus   pubis 213 

X30.   Hypertrophy  of  the  Mamm^  (Debierre,  Simes'  translation), 216 

131.  Liver,  Showing  Cirrhosis  with  Advanced  Fatty  Infiltration 225 

132.  Heart,   Extreme  Fatty  Infiltration, 226 

133.  Pseudohypertrophic  Muscular  Paralysis;    Fatty  Infiltration  of  Muscle 

(Fltxtterer) 227 

134.  Universal  Lipomatosis, 227 

135.  Liver,    Showing    Fairly    Advanced    Lardaceous    Disease;     the    Organ 

Weighed   1 7   Pounds, 228 

136.  Section  of  Lung  Showing  Infiltration  of  the  Connective  Tissue  of  the 

Alveolar  Wall  by  Coal-dust   (Anthracosis)    (Rindfieisch), 232 

137.  Section  of  a  Lung  Showing  Chalicosis 233 

138.  Cloudy  Swelling  of  the  Epithelial  Lining  of  the  Kidney  Tubule  (Flat- 

terer),       242 

139.  Granular  Degeneration  of  a  Muscle-Fiber,   Last   Stage,   Nearly  Fatty 

(Schmaus) 242 

140.  Cloudy  Swelling  of  the  Liver  Cells  (Schmaus) 242 

141.  Kidney,  Early  Stage  of  Fatty  Degeneration  of  the  Epithelium  of  the 

Convoluted  Tubes;  from  a  Case  of  Pernicious  Anemia, 243 

142.  Heart,    Transverse    and    Oblique    Sections    of    Muscle-fibers,    Showing 

Fatty  Degeneration, •      244 

143.  Intercostal  Muscle,  Transverse  Section,  from  a  Case  of  Epipneumonic 

Pluerisy,   Showing  Area  of  Coagulation  Necrosis 251 

144.  Fat  Necrosis  Accompanying  Acute  Hemorrhagic   Pancreatitis 253 

145.  Confluence  of  Two  Tubercles.      Section  of  Lung 255 

146.  Termination  of  Aorta,  the  Common  Iliac,  External  and  Internal  Iliacs, 

Case  of  Thrombo-arteritis  Due  to  Parauterine  Inflammation  and  Ex- 
tension to  the  Vessels  from  Adjacent  Tissues, 274 

147.  Section  Through  a  Part  of  a  Vein  with  its  Contained  Organizing  Throm- 

bus  (Schmaus) 275 

148.  Transverse  Section  of  a  Thrombosed  Blood-vessel  in  Which  Organi- 

zation and  Canalization  of  the  Thrombus  Are  in  Progress, 276 

149.  Branch  of  Pulmonary  Artery  Containing  Sarcoma  Cells  from  a  Case  of 

Wide-spread  Dissemination  of  a  Tumor  Primary  in  the  Subcutaneous 
Tissue  of  the  Thigh 278 

150.  Scheme  Illustrating  the  Formation  of  an  Anemic  Infarct  by  Obstruc- 

tion of  a  Terminal  Artery  (Chantemesse  and  Podwyssotsky), 2 So 

151.  Scheme  Illustrating  the  Formation  of  a  Hemorrhagic  Infarct  as  a  Re- 

sult  of  Obstruction  in  a  Terminal  Artery   (Chantemesse  and   Pod- 
wyssotsky),  _. 281 

152.  Part  of  Spleen  the  Seat  of  Multiple  Infarcts, 282 

153.  Kidney,  Multiple  Anemic  Infarcts, 282 

154.  Lung,   Hemorrhagic  Infarct   (Natural  Size), 283 

155.  Leukocytes  of  a  Frog   (Stohr), 289 

156.  Polymorphonuclear  Leukocytes  from  Center  of  Infiltrated  Area  in  a 

Section  of  the  Cerebral  Cortex  and  Meninges  from  a  Case  of  Suppura- 
tive Meningitis 290 

157.  Mononuclear  Cells  from  Meninges  in  a  Case  of  Meningitis, 290 

158.  Kidney,  Chronic   Interstitial  Nephritis 297 

159.  Karyo'kinetic  Figures  Observed  in  the  Epithelium  of  the  Mouth  Cavity 

of  a  Salamander   (Stohr), 301 

160.  Cellular  Elements  of  Formative  Tissue   (Schmaus) 302 


LIST    OF    ILLUSTRATIONS.  Xxi 

F'G.  Paoe 
It) I.  Granulation    Tissue.     Later    Stage    in    Organization    than    Fig.   160 

(Schmaus) ^04 

162.  The  Formation  of  Capillaries  in  Embryonic  Tissue  (Landois) 305 

163.  Section   Through   the    Border  of  a   Healing    Wound    (Diagrammatic) 

(Rindtieisch) ^oO 

164.  Small   Intestine, \  i  j 

165.  Papilloma  (Gould), 31O 

166.  Papilloma  with  Tendency  toward  Villous  Formation  (Schmaus), 317 

167    Adenoma  of  the  Cervix  Uteri 319 

1 68.  Fusiform  Myxoneuroma  of  the  External  Popliteal  Nerve, 321 

169.  Glioma  (Gould), 321 

170.  Scirrhous  Carcinoma  of  Mamma 323 

171.  Squamous  Epithelioma  (Gould) 326 

172.  Section  of  Squamous  Epithelioma  (Rindfleisch) 326 

173.  Cylindric-cell  Cancer  of  the  Stomach 327 

174.  Section  of  Cylindric-cell  Carcinoma  of  the  Liver, 328 

175.  Cylindric-cell  Epithelioma  of  the  Cervix   Uteri 330 

176.  Part  of  Cutaneous  Surface  of  Right  Mamma,  the  Seat  of  a  Centrally 

Placed,  Primary  Scirrhous  Carcinoma  and  of  a  Secondary  Nodule ".  332 

177.  Carcinoma  of  the  Mamma;    Axial  Section  through  the  Nipple  in  Line 

from  Sternum  to  Axilla 333 

178.  Glandular  Carcinoma  of  the  Liver  (Scirrhus) 334 

179.  Carcinoma  Arising  in  a  Mamma  the  Seat  of  Cystic  Disease, 335 

iSo.   Encephaloid  Carcinoma   (Soft  Cancer)   (Gould) 336 

iSi.  Glandular  Carcinoma  in  Which  the  Stroma  Has  Been  Converted  into 

Mucoid  Tissue  (Gould), 336 

182.   Colloid  Cancer  (Rindfleisch), 337 

183  and   184.  Diffuse  Lipoma  of  Neck, 338 

185.  Lipoma  (Gould), 339 

186.  Chondroma  (Gould), 340 

187.  Soft  Fibroma, 341 

188.  Neurofibromatosis   (Pode), 342 

189.  Secti(3n  (Longitudinal)  of  the  Uterus,  Showing  Myxomatous  Enlarge- 

ment  ". 343 

190.  Leiomyoma  (Gould), 344 

191.  Cavernous  Hemangioma  from  the  Wall  of  Bronchial  Cyst 346 

192.  Myxoma, 348 

193.  Lung,  Part  of  Serous  Surface;  Secondary  Sarcoma, 349 

194.  Lung,   Incised  Surface  of  Part  of  One  Lobe,  Secondary  Sarcoma,...  351 

195.  Round-cell  Sarcoma  (Rindfleisch), 352 

196.  Round-cell  Sarcoma  (Gould) 353 

197.  Round-cell  Sarcoma  of  a  Lymph-node  (Gould) 353 

198.  Spindle-cell   Sarcoma  (Gould) 353 

199.  Sarcoma  of  the  Mammary  Gland;    Tumor  o£  Several  Years'  Duration; 

Patient  Thirty-five  Years  of  Age, 354 

200.  Sarcoma,    Mixed-cell,   with  Calcihcation   of   Part   of  the    Intercellular 

Matri.x;     Osteosarcoma 355 

201.  Giant-cell    Sarcoma, 355 

202.  Alveolar  Sarcoma  (Gould) 356 

203.  Melanotic  Sarcoma  Springing  from  the  Subcutaneous  or  Possibly  from 

the  Periosteal  Connective  Tissues, 357 

204.  Alveolar  Melanotic  Sarcoma    (Gould) 357 

205.  Cerebrum,     Coronal     Section,     .Anterior     Aspect;      Superior    Parietal 

Lobule  and  Posterior  Part  of  Temporal   Lobe 358 

206.  Mamma,  Lymphangio-endothelioma 350 

207.  Mamma,  Lymphangio-endothelioma, 360 

208.  Perithelioma  of  the  Carotid  Body "i'>i 

209.  Perithelioma    of  the  Carotid  Body i'->2 

210.  Teratoma, ^'^4 

211.  Teratoma  of  Testicle, .^'>5 

212.  Syncytioma, 3^5 

213.  Gowers'  Hemoglobinometer.   Improved  Form; 390 

214.  Von  Fleischl's  Hemoglobinometer, 301 

215.  Oliver's  Hemoglobinometer, '-•~>2 

216.  Dare's    Hemoglobinometer, ,>m4 


XXll  LIST    OF    ILLUSTRATIONS. 

Fig.  Page 

217.  Dare's  Hemoglobinometer,  Horizontal  Section, 395 

218.  Thoma-Zeiss  Hemocytometer, 399 

219    Capillary  Mixing  Tube  of  the  Thoma-Zeiss  Apparatus  (Jaksch), 400 

220.  Mixing  Tube  of  Galli 401 

221.  Counting  Chamber  of  the  Thoma-Zeiss  Hemocytometer  (Landois) 401 

222.  Hematocrit  Tube 403 

223.  Rotating  Frame  of  the  Hematocrit, 403 

224.  A  Method  of  Filling  the  Centrifuge  Tube, 404 

225.  Diagrammatic   Representation   of   Various   Forms   and   Sizes   of   Red 

Cells, 407 

226.  Types  of  Red  Blood-cells;  also  Leukocytes  (Landois) 408 

227.  Poikilocytes 408 

228.  Crenated  Red  Blood-corpuscles  (Landois), 409 

229.  Diagrammatic  Representation  of  Leukocytes 412 

230.  Spleen  Consisting  of  Two  Parts  Joined  by  Fibrous  Band, 433 

231.  Hodgkin's  Disease 448 

232.  Heart  Showing  Villous  Pericarditis;    Ascending  and  Transverse  Por- 

tion of  Arch  of  Aorta,  Showing  Aneurysm  with  Contained  Clot,  and 

Ruptures  into   Pulmonary  Artery  and  Pericardium 464 

233.  Vertical  Section  Through  an  Inflamed  Serosa  after  the  Formation  of  the 

Fibrinous  Exudate  (Schmaus), 465 

234.  Intercostal  Muscle, 466 

235.  Intercostal  Muscle,  Case  of  Empyema, 466 

236.  Pericardium     (over    auricle);      Acute    Serofibrinous    Pericarditis    En- 

grafted on  a  Serosa  the  Site  of  Past  Inflammations, 467 

237.  Section  Through  Margin  of  Adhesion  between  Parietal  and  Visceral 

Pleura 468 

238.  Intestine.     Chronic  Adhesive  Peritonitis, 472 

239.  Lung.     Chronic    Interstitial    Pneumonia,    Bronchiectasis,    Hyalosero- 

sitis, and  a  Terminal  Catarrhal  Pneumonia  Due  to  Mixed  Infection 

by  the  Tubercle  Bacillus  and  Pneumococcus, 474 

240.  Acute  Tuberculous  Pericarditis,  Vertical  Section  of  Inflammatory  Exu- 

date  (Schmaus"), .*....  477 

241.  Chronic,  Adhesive,  Indurative,  and  Caseous  Tuberculous  Mediastino- 

pericarditis.     Heart  and  Adjacent  Mediastinal  Structures 478 

242.  Pectoral  Heart 484 

243 .  Malformation  of  the  Heart, 486 

244.  Heart  Showing  Absence  of  Anterior  Portion  of  Auricular  Septum 486 

245.  Heart,  Great  Vessels,  and  Lungs  from  a  Case  of  Transposition  of  the 

Vascular  Trunks, 487 

246.  Fatty  Infiltration  of  the  Heart  and  Partial  Pericardial  Adhesion 489 

247.  Fatty  Degeneration  of  the  Heart 492 

248.  Diagram  Showing  the  Distribution  of  the  Coronary  Artery  in  a  Case 

of  Local  Fibroid  Myocarditis, 496 

249.  Arteriosclerotic  Disease  of  the  Coronary  Artery  Giving  Rise  to  Pro- 

gressive Obliteration  of  its  Lumen, 497 

250.  Chronic  Myocarditis   (Schmaus) 497 

251.  Heart,   Elastic  Myocarditis, 499 

252.  Heart,   Elastic  Myocarditis 500 

253.  Aortic  Orifice  Laid  Open,  Showing  the  Valve  Leaflets,  Acute  Endocar- 

ditis  (redrawn  from   Schmaus), 507 

254.  Acute    Endocarditis   of   the    Mitral   Valve,    Section   at    Contact    Line 

(Rindfleisch), 508 

255.  Narrowed   Mitral   Orifice,    Showing   Results   of  Adhesions  with   Con- 

siderable Fibroid  Thickening  (Buttonhole  Mitral) 509 

256.  Adjacent  Aortic  Cusps,  Showing  a  Small  Vegetation  Developing  Just 

Below  the  Point  of  an  Old  Adhesion, 511 

257.  Adherent  and  Thickened  Valve  Leaflets  (Rindfleisch), 513 

25S.   Heart  and  Aorta  of  Rabbit,  Adrenalin  Atheroma,  and  Multiple  Aneur- 
isms   521 

259.  Aorta,  Opened,  Showing  Different  Types  of  Atheroma 522 

260.  Obliterative  Endarteritis 523 

261.  Coronary  Artery,   Showing  Arterial  Sclerosis, 526 

262.  xVrtery,  Early  Stage  of  Arteriosclerosis 527 


1 


LIST    C)l-     ILLUSTRATION'S.  Xxiii 

Fio.  lAi.r. 

263.  Artery,  Arteriosclerosis ^3^ 

264.  Artery,  Advanced  Arteriosclerosis ^27 

265.  Thoracic  Aneurysm qjo 

266.  Symmetric  Aneurysm  of  the  Abdominal  Aorta 532 

267.  Varicose  Veins  of  the  Leg :^35 

268.  Section  of  the  Lung,   Pneumoconiosis  (Rindfieisch) 543 

269.  Section  of  Lung  showing  Chalicosis   (Schmaus) 544 

270.  Granular  Degeneration  (Cloudy  Swelling)  of  the  Liver  Cells  (Schmaus), . .  545 

271.  Fatty  Defeneration  of  the  Liver  Cells  (Schmaus) 545 

272.  Granular  Degeneration  of  the  Kidney  Epithelium  (Cloudy  Swelling) 

(Schmaus) 545 

273.  Section  of  Wall  of  Bronchus,  Chronic  Bronchitis 549 

274.  Margin  of  Pseudomembrane  from  Tonsil,  Case  of  Diphtheria,. . . , 551 

275.  Vertical  Section  through  the  Pseudomembrane  and  Part  of  the  Wall 

of  the  Larynx  in  Pseudomembranous  Laryngitis  (Schmaus) 552 

276.  Fibrinous    Cast    from    the    Bronchi,    Case    of    Croupous    Pneumonia 

(Schmaus), 553 

277.  Hemorrhagic  Colitis 555 

278.  Uterus,  Case  of  Septic  Endometritis  with  Extensive  Necrosis  of   the 

Endometrium  and  Myometrium,  due  to  Postpartum  Infection 556 

279.  Uterus,  Section  from  Specimen  shown  in  Fig.   278 557 

280.  Vertical  Section  of  Mucous  Membrane,  Showing  Diphtheric  or  Gan- 

grenous Inflammation,  from  a  Case  of  Dysentery  (Schmaus) 558 

281.  Intestine,  Chronic  Secondary  Tuberculosis;    Irregular  Ulcers  the  Floors 

of  Which  Present  a  Necrotic  Surface 560 

282.  Margin  of  Tuberculous  Ulcer  of  the  Intestine, 561 

283.  Pseudomembranous    Laryngitis   and   Tracheitis   due    to    the    Bacillus 

diphtherias, 570 

284.  Tuberculous  Ulcer  of  the  Mucous  Membrane  of  the  Trachea 571 

285.  Perichondritis,    Necrosis,  and  Laryngeal  Ulceration 572 

286.  Tracheal   and   Partial   Laryngeal   Stenosis   Following  Cicatrization   of 

a  Gumma 573 

287.  Trachea  of  Child  (Age  Eleven  Years)  Showing  Carcinoma  Extending 

through  the    Wall  as  an  Irregular  External  Mass 574 

288.  Lung,  including  a  Small   Bronchus.      Bronchitis  and  Beginning  Lobu- 

lar or  Bronchopneumonia 376 

289.  Chronic  Caseous  Bronchitis,    TuVjerculous  Bronchitis,  Caseous  Soften- 

ing  of  the    Bronchial    Wall,   with   Thickening   of   the    Peribronchial 

Tissue.   Peribronchitis  Chronica  (Schmaus) 577 

290.  Lung,  Emphysema  and  Bronchiectasis 580 

291.  Lung,   Hemorrhagic  Infarct 586 

292.  Pulmonary  Emphysema  (Flutterer) ^gi 

293.  Lung,  Emphysema 592 

294.  Part  of  Right  Lung,  Circumscribed  Gangrene, 596 

295.  Sputum,   Croupous  Pneumonia 598 

296.  Three  Alveoli  Filled  with  Fibrinous  Exudate.     Croupous  Pneumonia. 

Stage  of  Hepatization   (Schmaus) 601 

297.  Croupous  Pneumonia.     Single  Air-Vesicle  in  the  Second  Stage,  with 

Slightly  Contracted  Exudate 602 

298.  Lung,  Croupous  Pneumonia,  Organization  of  the  Intravesicular  Exu- 

date   604 

299.  Lung,    Including   a    Small    Bronchus.     Bronchitis   and    Bronchopneu- 

monia   609 

300.  Two  Alveoli  and  a  Part  of  a  Third  from  Lung  in  Catarrhal  Pneu- 

monia   610 

301.  Lung,    Chronic     Interstitial     Pneumonia,     Bronchiectasis,    Hyalosero- 

sitis,   and    a   Terminal   Catarrhal    Pneumonia    Resulting    from   Con- 
current Infection  by  the  Tubercle  Bacillus  and  Pneumococcus 613 

302.  Tuberculous  Pneumonia, 615 

303.  Lung.    Chronic    Caseous    and    L'lceratin^   Tuberculosis   of   the   Ajjex; 

Tuberculous  Bronchitis,  and  a  Miliary  Tuberculosis 616 

304.  Tuberculosis  of  the  Lung •  .  6ig 

305.  Lung,   Chronic  Ulcerative  Tuberculosis  of  Upper  Lobe:    Acute  Mili- 

ary Tuberculosis  as  a  Terminal  Lesion  Involving  the  Entire  Organ: 


XXIV  LIST    OF    ILLUSTRATIONS. 

Fig.  Page 
Slight     Interstitial     (Fibroid)      Pneumonia;      Chronic     Tuberculous 
Peribronchitis;      Bronchiectasis;     Acute    Pseudomembranous    Bron- 
chitis;   Chronic  Fibrohyalopleuritis, 621 

306.  Wall  of  a  Tuberculous  Cavity   (Schmaus), 622 

307.  Branch  of  Pulmonary  Artery  Containing  Sarcoma  Cells  from  a  Case 

of   Wide-spread   Dissemination  of  a  Tumor   Primary  in  the   Subcu- 
taneous Tissue  of  the  Thigh 625 

308.  Lung,   Part  of  Serous  Surface;    Secondary  Sarcoma 626 

309.  Lung,   Incised  Surface  of  Part  of  One  Lobe,   Secondary  Sarcoma,...  627 

310.  Longitudinal  Section  of  the  Kidney  (Tyson,  after  Henle), 62S 

311.  Diagram   of   Blood-supply  to  Kidney    (Rindfleisch) 629 

312.  Solitary  Kidney 630 

313.  Horseshoe  Kidney 630 

314.  Persistent    Fetal    Kidney    due    to    Anastomoses    Between    the    Renal 

Artery  and  Vein 631 

315.  Kidney,   Showing  Granular  and  Fatty  Degenerations  of  the  Cortex, 

from  a  Case  of    Pernicious   Anemia, 636 

316.  Cloudy   Swelling   of  the   Epithelium   Lining   a   Kidney  Tubule    (Fliit- 

terer) 636 

317.  Kidney,    Multiple    Anemic    Infarcts.     Case    of    Ulcerative    Endocar- 

ditis,'   638 

318.  Kidney,  Acute  Suppurative  Interstitial  Nephritis,... 642 

319.  Kidney,  Acute,   Nonsuppurative,   Interstitial  Nephritis, 646 

320.  Chronic  Parenchymatous  Nephritis, 650 

321.  Kidney,   Showing  Chronic  Diffuse  Nephritis, , 651 

322.  Kidney,   Showing  Chronic  Interstitial  Nephritis, 652 

323.  Kidney  Showing  Advanced  Chronic  Interstitial  Nephritis 654 

324.  Kidney,  Chronic  Interstitial  Nephritis 655 

325.  Kidney,  Chronic  Interstitial  Nephritis 656 

326.  Kidney,  Chronic   Interstitial  Nephritis  and  Lardaceous  Disease 657 

327.  Tuberculous  Pyelonephritis;  'Chronic  Tuberculosis  of  the  Kidney 661 

328.  Hypernephroma.      (Case  Reported  by  Dr.   Keen) 662 

329.  Section  of  Hypernephroma,   Showing  Capsule, 663 

330.  Section  of  Hypernephroma,   Showing  Character  of  Cells 664 

331.  Hydronephrosis 664 

332.  Congenital  Cystic  Disease  of  the  Kidney, 665 

333.  Kidney,  Congenital  Cystic  Disease;  Laid  Open, 666 

334.  Congenital  Cystic  Disease  of  the  Kidney, 667 

335.  Congenital  Cystic  Disease  of  the  Kidney, 667 

336.  Congenital  Cystic  Disease  of  the  Kidney;    Part  of  Wall  of  a  Larger 

Cyst 668 

337.  Loss  of  Tissue  due  to  Noma, 677 

338.  Tongue,    Pharynx,    Epiglottis,    etc.,    from   Case    of    Ludwig's   Angina 

due  to  the  Pneumococcus, 680 

339.  Section  from    Right    Parotid 687 

340.  Section  of  the  Left  Parotid  under  a  Very   Low  Power, 688 

341.  Mixed  Tumor  of  the  Parotid  Gland, 689 

342.  Squamous-Cell  Carcinoma  of  the  Esophagus;   Polypoid  Type, 694 

343.  Stomach;  Hour-glass  Contraction  Secondary  to  Gastric  Ulcer, 697 

344.  Stomach,  Chronic  Catarrhal  Gastritis  with  Erosions, 700 

345.  Stomach,    Chronic   Catarrhal   Gastritis   with   Erosions;     Vertical   Sec- 

tion Through  an  Erosion, 701 

346.  Perforated  Peptic  Ulcer  of  Stomach   (Gastric  Ulcer) 705 

347.  Stomach,  Carcinoma  of  Pylorus,  with  Secondary  Nodules  in  the  Retro- 

gastric  Glands;  External  Surface, 710 

348.  Stomach,  Carcinoma  of  Pylorus,  with  Secondary  Nodules  in  the  Retro- 

gastric  Glands, 710 

349.  Pyloric  End  of  Stomach;     Marked   Stenosis  of   Pylorus  due   to  Con- 

traction of  Scirrhous  Carcinoma 711 

350.  Intussusception  at  Ileocecal  Valve, 716 

351.  Intussusception  Diagram  Intended  to  Show  the  Relation  of  the  Several 

Parts  in  Fig.   350 7^7 

352.  Hemorrhagic  Colitis   (Harris) 723 

353.  Perforating  Ulcer  of  Colon   (Amebic  Dysentery), 726 


LIST    or     ILIA'STRATIONS.  XXV 

354.  Amebic  Dysentery  in   Puppy  (Third  to  Fourth   Day)   (Harris), 727 

355.  Small    Intestine.     Typhoid    Ulcer    during    the    Early    Part    o£    Third 

Week  of  the  Disease 728 

356.  Section  through  a  Typhoid  Ulcer,  End  of  Second    Week  of  the  Dis- 

ease (Schmaus) 729 

357.  Section  of  the  Intestinal  Wall  at  the  Edge  of  a  Typhoid  Ulcer,  Be- 

ginning of  Third  Week  of  the  Disease ' 730 

358.  Small     Intestine;      Secondary     Tuberculosis;      Multiple     Tuberculous 

Ulcers 732 

359.  Tuberculous  Ulcer  (Schmaus), 733 

360.  Hyperplastic  Tuberculosis  of  Small  Intestine, 7^4 

361.  Liver,  Advanced  Red  Atrophy ;  1 1 

362.  Liver,  Cirrhosis  and  Marked  Fatty  Infiltration 7ti 

363.  Liver,  Fairly  Advanced  Lardaceous  Disease, 7  ; 

364.  Multiple  Amebic  Abscess  of  Liver, ;    i 

365.  Liver,   Wall  of   an  Amebic  Abscess 752 

366.  Superior  Aspect  of  Liver,  Showing  Unusual  Degree  of  Cirrhosis  with 

"Hob-nailed  "   Surface 754 

367.  Atrophic  Cirrhosis  of  the   Liver,   Advanced   (Schmaus) 755 

368.  Under  Surface  of  Liver  Showing  Results  of  Congenital  Syphilis 759 

369.  Syphilitic  Cirrhosis  of  the   Liver  (Schmaus) 760 

370.  Part  of  Left  Lobe  of  the  Liver,  Showing  Primary  Cylindric-cell  Carci- 

noma   762 

371.  Acute  Pancreatitis  with  Fat -necrosis  (Douglas),' 770 

372.  Fat-necrosis  Accompanying  Acute  Hemorrhagic  Pancreatitis 771 

373.  Pancreas   Showing    Increase   of   Fibrous   Tissue.     Chronic    Interstitial 

Pancreatitis 772 

374.  Thyroid  Gland,  Absence  of  Isthmus  (Marshall,  courtesy  of  Dr.  Richard- 

son),       776 

375.  Thyroid  Gland.  Large  Pyramid,  So-called  Pyramidal  Lobe  (Marshall, 

courtesy  of  Dr.   Richardson) 776 

376.  Thyroid  Gland  Showing  Double  Pyramid  (Marshall,  courtesy  of  Dr. 

Richardson) '. 777 

377.  Thyroid  Gland,  Absence  of  Isthmus  with  Pyramid  on  Left  Side  (Mar- 

shall, courtesy  of  Dr.   Richardson) 777 

3  78.   Intrathoracic    Goiter    Developed    from    Ectopic    Thyroid    (Dittrich, 

courtesy  of  Dr.   Richardson) 778 

379.  Cretin  Aged  Twenty-two  Years   (Wagner,   courtesy  of  Dr.   Richard- 

son),       7  7Q 

380.  Unusually  Large  Cystic  Goiter 78 1 

38 1.  Goiter   (Bilateral)   Causing   Compression   of  the   Windpipe    Producing 

the  So-called  "Bayonet-shaped"  Trachea  (Demme,  courtesy  of  Dr. 
Richardson) 7S2 

382.  Exophthalmic  Goiter,    Basedow's  Disease   (Courtesy  of  Dr.    Richard- 

son)   ■ 783 

383.  Section  of  Cortex  of  Kidney  Containing  Ectopic  Adrenal 784 

384.  Section  of  Ectopic  Adrenal  Beneath  the  Peritoneum  and  Intimately 

Attached  to  the  Capsule  of  the  Liver 785 

385.  Section  Taken   from  the  Gastrocnemius  Muscle  of  a  Child  Suffering 

from   Pseudohypertrophic  Muscular  Paralysis, 780 

386.  Progressive  Muscular  Dystrophy,  Erb  Type. 790 

387.  Intercostal  Muscle,  Acute,  Nonsuppurative,  Interstitial  Myositis 792 

38S.  Myositis,  Acute  Diffuse  Suppurative.     Case  of  Ludwig's  Angina 793 

389.  Intercostal  Muscle roa 

390.  Ossifying  Myositis 

391.  Ossifying  Myositis 

392.  Section  of  Bone-marrow  of  Rabbit,  Showing  the  Delicate  Conncclivc- 

tissue  Reticulum  Containing  the  Different  Elements  of  the  Marrow 

(Schafer) "     ' 

393.  Elements  of  Human  Bone-marrow  (Stdhr) 

394.  Achondroplasia  (Comby,  courtesy  of  Dr.   Richards' >:. >di 

395.  Chronic  Productive  Osteoperiostitis • ^o>, 

396.  Acromegaly, >*07 

397.  Osteophytes  on  the  Popliteal  Aspect  of  the  Lower  End  of  the  Femur 808 


XXVI  LIST    OF    ILLUSTRATIONS. 

Fig.  Page 

398.  Osteomyelitis   Involving   the   Tibia,    and,    to   a   Limited   Extent,   the 

Lower  End  of  the   Femur 813 

399.  Exterior  of   Femur,    Showing   Result   of   Chronic   Osteitis   Associated 

with  Chronic  Productive  Periostitis 816 

400.  Femur.      Longitudinal  Section  of  Bone  Shown  in  Fig.   399 816 

401.  Femur,  Head  and  Neck;   Beginning  Tuberculosis, .  818 

402.  Fracture  of  the  Femur,  Showing  Overlapping  of  the  Fragments  with 

Rotatory    Displacement    of    the    Lower    Fragment,    and    Attempted 

Union  in  this   Position 821 

403.  Ten-Day-Old  Fracture  (Schmaus), 821 

404.  Sarcoma,   ]\Iixed-Cell,  with  Calcification  of  Part  of  the   Intercellular 

Matrix;  Osteosarcoma, 824 

405.  Craniorrhachischisis  Totalis 842 

406.  Spina   Bifida, 845 

407.  Section  of  Cerebral  Cortex  and  Meninges  from  a  Case  of  Suppurative 

Meningitis 852 

408.  Spinal  Cord  and  Meninges, 855 

409.  Spinal  Cord   and   Meninges,    Dura  Laid   Open  on  Posterior  Surface; 

Case  of  Epidemic   Cerebrospinal   Meningitis 855 

410.  Section  of  Human  Brain  Including  Wall  of  Cerebral  Abscess 869 

411.  Disseminated  Sclerosis  in  Medulla, 874 

412.  Disseminated  Sclerosis  in  Cord 874 

413.  Sarcoma  of  Brain,  Gross  Specimen, 876 

414.  Sarcoma  of  Brain,  Microscopic  Section 876 

415.  Endothelioma  of  Pituitary  Body, 878 

416.  Secondary  Degeneration  of  Posterior  Column, 879 

417.  Spinal  Cord,  Areas  of  Sclerosis  due  to  Pernicious  Anemia, 880 

418.  Myelitis.     Areas  of  Softening  in  the  Cord 881 

419.  Spinal  Cord  Showing  Posterior  Sclerosis, 886 

420.  Nerve,  Acute   Interstitial  Neuritis, 890 

421.  Longitudinal    Section    of    Musculospiral    Nerve;     Alcoholic    Multiple 

Neuritis, 891 

422.  Neuritis  Due  to  Chronic  Lead  Intoxication  (Gordon), 891 

423.  Chronic    Interstitial    Neuritis  showing    Degeneration   in  Some   of   the 

Nerve-fibers 892 

424.  Moist  Chamber  for  Potato  Culture 899 

425.  Instrument  for  Cutting  Plugs  of  Potato  for  Potato  Culture, 900 

426.  Agate-ware    Water-bath, 900 

427.  Test-tube  Basket, 903 

428.  Double-walled  Hot-air  Sterilizer 903 

429.  Diagram  of  Interior  of  Hot-air  Sterilizer 903 

430.  Tube-filler, 904 

431.  Arnold  Steam  Sterilizer, 905 

432.  Autoclave  or  Digestor, 906 

433.  Blake  Bottle  for  Plating, 907 

434.  Dish  Devised  by  Petri, 907 

435.  Platinum  Inoculating  Needles  Mounted  on  Glass  Rods, 908 

436.  Method  of  Holding  Tubes,  Cotton  and  Platinum  Wire  while  Inoculating 

Solid  Media, 909 

437.  Apparatus  for  Counting  Colonies  (Pakes) 910 

438.  Hesse's  Aeroscope, 911 

439    and  440.     Two  Forms  of  Stewart's  Cover-glass  Forceps, 912 

441.  Kalteyer's  Cover-glass  Forceps, 913 

442.  Novy's    Apparatus    for    Anaerobic    Cultivation    of    Plates    and    Test- 

tubes,  917 

443.  Sternberg's  Anaerobic  Culture-tube, 917 

444.  Wright's  Method  for  Anaerobic  Cultivation  in  Liquid  Media, 918 

445.  Drop-culture  Slide, 919 

446.  Small  Incubator  Sufficiently  Large  for  Individual  Work, 922 

447.  Apparatus  for  Holding  a  Mouse  or  Rat  for  Inoculation, 924 

448.  Koch's  Syringe  for  Hypodermic,   Intraperitoneal  and  Other  Injection 

Methods  for  Inoculating  Animals, 925 

449.  Spatula  for  Searing  Surface  of  Organs 925 

450.  Sternberg's  Flask, 927 


LIST    OF    ILLUSTRATIONS.  XXvii 

Fig.  P^q, 

451.  Kitasato's  Filter 027 

452.  Bacillus  typhosus;   Widal  Test,   Negative  Reaction 930 

453.  Bacillus  typhosus;   Widal  Test.   Positive   Reaction 930 

454.  Bacillus  typhosus;   Widal's  Test,   Pseudo-reaction 931 

455.  Water  Centrifuge 035 

456.  Conical  Glass  Suitable  for  Sedimentation  of  Urine 936 

457.  Centrifuge  with  Hematocrit  Attachment 936 

458.  Phantom  and  Distorted  Red  Blood  Cells  Found  in  Urine 938 

459.  Blood  Cells  in   Urine 938 

460.  Blood  Cells  in  the  Urine,  Lymph  Corpuscles,  Leukocytes  of  Pus  Cells 

and  Crystals  of  Triple  Phosphates 938 

461.  Epithelium    from    the    Conducting    Part    of    the   Urinary   Apparatus, 

Mostly  from  the  Bladder, 938 

462.  Renal  (?)  Epithelium 938 

463.  Seminal  Elements,  Some  of  which  may  be  found  in  Urine 939 

464.  Illustrating  the  Formation  of  Casts, 939 

465.  Epithelial  Casts 939 

466.  Blood  Cells  and  Blood  Casts 940 

467.  Hyaline  and  Epithelial  Casts, 940 

468.  Granular  Casts 940 

469.  Leukocyte  and  Crystalline  Casts 940 

470.  Crystals  of  Uric  Acid.      Fungi 940 

471.  Some  Forms  of  Uric  Acid, 941 

472.  Acid  Ammonium  Urate, 941 

473.  Hippuric  Acid 941 

474.  Some  Deposits  in  Acid  Fermentation  of  Urine 941 

475.  Some  Deposits  from  Ammoniacal  Urine  (Alkaline  Fermentation) 941 

476.  Whetstone  and  Irregular  Crystals  of  Uric  Acid, 941 

477.  Ammonium  Urate 941 

478.  Stellate  and  Feathery  Crystals  of  "Triple  Phosphate 943 

479.  Forms  of  Crystals  of  Ammonio-magnesium  Phosphate 943 

480.  Ammonio-magnesium  Phosphate 943 

48 1 .  Magnesium   Phosphate, 943 

482.  Amorphous  Granules  of  Calcium  Carbonate 943 

483.  Oxalate  of  Lime 944 

484.  Amorphous    Granules,    Wedge-shaped    Crystals,    Some    of    which    are 

Arranged  in  Rosettes,  Calcium  Phosphate 944 

485.  Dumb-bell  and  Octahedral  Crystals  of  Calcium  Oxalate 944 

486.  Calcium  Sulphate 944 

487.  Cystin  and  Oxalate  of  Lime 944 

488.  Leucin  and  Tyrosin 945 

489.  Leucin  and  Tyrosin 945 

490.  Cystin 945 

491.  Cholesterin, 945 

492.  Indigo 945 

493.  Squamous  Epithelium 046 

494.  Curschmann's  Spirals, 047 

495.  Charcot-Leyden  Crystals,.. 048 


PART  I. 
TECHNIC 


PART  I.— TECHNIC. 

CHAPTER  I. 
POSTMORTEM  EXAMINATIONS.' 

I.  INSTRUMENTS  NEEDED. 

A  postmortem  may  be  made  with  a  very  few  instruments;  those 
supphed  in  an  ordinary  dissecting  case  may  suffice  for  the  examination 
unless  the  central  nervous  system  is  to  be  removed,  in  which  case  a  saw 
will  be  found  necessary.  Scarcity  of  instruments  is  rarely  a  justifiable 
excuse  for  failure  to  avail  one's  self  of  an  opportunity  to  hold  a  post- 
mortem. A  most  thorough  examination  may  be  made  with  a  knife  such 
as  is  ordinarily  used  by  butchers,  a  saw,  and  a  carpenter's  hammer  and 
chisel. 

The  instruments  and  apphances  given  in  the  following  list  may  be  pro- 
cured by  those  who  contemplate  making  postmortems,  the  extent  of  their 
purchase  being  largely  a  matter  of  taste  and  money  available.  The  in- 
struments marked  by  an  asterisk  are  considered  indispensable,  the  others 
being  conveniences  to  facilitate  or  lessen  the  labor: 

*  One  Virchow  yjostmortem  knife. 

*  Two  strong  scalpels. 

*  Two  small  scalpels;   one  probe-pointed. 

One  costotome,  or,  when  this  can  not  be  obtained,  a  cartilage  knife 
or  a  saw  may  be  substituted. 

*  At  least  two  dissecting  forceps :  one  with  corrugated  Vilades  and 
one  with  rat-toothed  blades.  A  number  of  such  instruments  will  be 
found  useful. 

*  One  pair  of  scissors:   one  blade  sharp  and  one  probe-pointed. 

One  enterotome,  or.  when  this  is  not  available,  a  small  cork  or  piece 
of  wood  may  be  pushed  over  the  tip  of  the  sharper  {minted  blade  of  the 
ordinary  scissors. 

Two'  long  probes:  one  should  have  an  eye  and  one  should  be  quite 
slender;  the  latter  is  convenient  for  tracing  ducts.  An  instrument  to  be 
commended  is  a  combined  grooved  director  and  probe.  For  the  exami- 
nation of  sinuses  and  whenever  it  can  be  employed,  there  is  no  instru- 
ment that  can  be  used  to  better  advantage  than  the  trained  finger. 

*  One  saw  with  a  well-bellied  cutting-edge. 

*  One  grooved  director. 

'  The  student  wishing  to  add  to  the  ff)lIo\vin}^'  ci)itome  of   postmort. 
nic  should  consult  "La  Pratifjue  des  Autopsies."  by  Letulle.  "Manuel  • 
et  pratique  des  autopsies,"  bv  Zilgien.  "  Patholosji.'^ch-anatonusche  Dia.u''— "•  - 
bv  Orth,  "Sections-Technik,"  bv  Xauwerck.      Postmortem   Patholog>-.  '  by  Cat- 
tell,  and  "Pathological  Technique,"  by  Mallon.'  and  Wright.     The  authr.r  has  in 
preparation  a  manual  dealing  with  autopsy  and  laborator>-  technic. 


2  TECHNIC. 

*  Two  large  postmortem  needles. 

*  Two  spools  of  flaxed  thread:   one  white,  one  black. 

*  One  mallet ;  the  rawhide  mallet  has  the  advantage  of  making  but 
little  noise  when  used  on  the  chisel.  The  steel  hammer  ordinarily  sup- 
plied with  postmortem  cases  has  a  blunt  hook  on  the  handle,  which  is 
useful  for  removing  the  calvaria,  and  occasionally  for  other  purposes. 
The  objectionable  noise  made  by  pounding  on  a  metalHc  chisel  may  be 
overcome,  at  least  partly,  by  covering  the  chisel  with  a  folded  towel. 

One  chisel.  Of  the  various  forms  of  chisels  recommended,  the  lower 
one  in  figure  22  will  be  found  most  useful.  Some  of  the  forms  of  hatchet- 
chisel,  however,  will  be  occasionally  used. 

A  brass  or  German-silver  ruler,  graduated  in  inches  and  in  centi- 
meters, win  be  found  useful.  Such  a  ruler  should  be  at  least  twenty 
centimeters  in  length,  and  the  graduation  throughout  should  be  in 
tenths;  a  finer  graduation  on  instruments  of  this  kind  can  rarely  be 
read  at  the  postmortem  table.  As  a  result  of  attempts  to  reduce  the 
number  of  instruments  contained  in  the  postmortem  case,  the  writer 


Fig.  I. — Complete  Postmortem  Case. 
It  is  convenient  to  have  a  leather  covering  for  the  case. 

has  had  the  long,  thin-bladed  brain  knife,  shown  in  figure  14,  graduated 
along  its  back.  As  the  instrument  is  useful  for  incising  organs,  the 
graduation  is  convenient  and  always  at  hand. 

A  double  rachiotome  is  a  very  useful  instrument,  but  is  not,  how- 
ever, convenient  for  carrying  to  private  postmortems. 

A  strong  bone  forceps  will  occasionally  be  needed. 

Measures  of  Capacity. — Small  graduates  measuring  from  o.i  c.c.  to 
50  c.c.  will  be  found  useful.  Larger  measures  should  be  at  hand.  Any 
agateware  or  tin  vessel  (the  former  is  preferable)  may  be  standardized 
by  a  smaller  graduate,  and  being  very  much  less  fragile  and  less  expen- 
sive, is  therefore  to  be  preferred. 

A  syringe  for  sucking  up  fluid  from  the  bottom  of  cavities  not  easily 
accessible  is  a  convenience. 

Postmortem  Room. — In  well-appointed  hospitals,  morgues,  etc.,  a 
room  is  usually  set  apart  for  postmortems.  This  room  should  be  well 
lighted  and  capable  of  thorough  ventilation.  The  floor  should  be  of  imper- 
meable concrete,  the  walls  tiled  or  Ijuilt  of  enameled  brick,  or,  in  the 


POSTMORTEM   EXAMINATIONS.  3 

absence  of  these,  covered  by  lusterless  white  enamel  paint.  A  capacious 
postmortem  table  should  be  so  placed  in  the  room  as  to  be  well  lighted  and 
accessible  on  all  sides.  The  size  of  the  taljle  is  often  a  matter  of  individ- 
ual preference.  The  table  preferred  by  the  writer  is  three  feet  wide,  six 
feet  long,  substantially  constructed,  zinc  or  slate  covered,  the  covering 
sHghtlv  raised  at  the  edges  of  the  table,  and  the  top  gently  sloj)ing 
toward  a  large  grate-covered  drain  in  the  center.  This  drain,  thor- 
oughlv  trapped,  may  be  directly  connected  with  the  sewage  pipes,  and 
may  be  so  attached  to  the  ventilation  system  as  to  secure  a  strong 
downward  draft,  thus  drawing  downward  all  odors  which  would  other- 
wise rise  and  permeate  the  room.  For  convenience  in  measurements  a 
centimeter  and  inch  scale  may  be  ruled  upon  the  edge  of  the  table. 

Although  never  to  be  used  when  it  can  be  avoided,  an  abundance 
of  artificial  light  should  be  at  command.  The  best  artificial  light  for 
the  postmortem  room  is  afforded  by  Welsbach  burners  with  porcelain 
reflector  and  shade  or  Nernst  incandescent  electric  bulbs;  thirty-two 
candle-power  incandescent  lamps  with  thoroughly  frosted  globes  are 
objectionable  substitutes  for  natural  light.  All  forms  of  artificial  light 
so  modify  the  color  of  organs  as  often  to  afford  misleading  pictures  to  the 
uninitiated. 

Water-supply. — Suspended  just  above  the  autopsy  taV)le  and  coming 
down  to  within  an  inch  or  so  of  the  table  should  be  a  rubber  hose  con- 
nected with  proper  metallic  fixtures,  so  arranged  as  to  afford  a  mixing 
device,  by  means  of  which  hot  and  cold  water  can  be  mixed  and  delivered 
through  the  rubber  tube  at  any  temperature  that  may  be  desired.  B>' 
permitting  the  rubber  tube  to  project  practically  to  the  table  the  end 
can  be  kept  in  a  pan,  thus  affording  a  small  reservoir  of  constantly  clean 
water.  The  flexible  rubber  hose  affords  facilities  for  washing  the  table 
and  cleaning  the  instruments  and  appliances. 

A  capacious  sink  in  some  part  of  the  room  is  desirable;  into  this 
should  drain  a  slate  dripping-slab  sixty  centimeters  wide  and  two  meters 
long. 

Two  scales  should  be  at  command — one  for  weighing  from  a  fraction 
of  a  gram  to  ten  or  twenty  grams,  the  other  for  heavier  masses.  Al- 
though rarely  at  hand,  a  scale  for  weighing  l)odies  is  desirable.  Scales 
for  weighing  organs  and  tissues  should  have  large  brass  pans  that  can 
be  readily  cleaned. 

A  head  block  twelve  inches  long  and  six  inches  square,  with  a  notched 
depression  near  the  center  for  receiving  the  neck,  will  be  found  useful  in 
supporting  the  head,  and  similar  blocks  may  be  used  for  arching  the 
body  during  the  examination  of  the  spine  and  the  removal  of  the  cord. 

Heavy  boards,  fifty  by  sixty  centimeters,  will  be  found  serviceable 
for  the  support  of  organs  during  section. 

A  vise  will  be  occasionallv  needed. 

Of  the  various  forms  of  head  holders  in  the  market,  the  writer  has 
never  felt  that  any  was  better  than  the  hand. 

Every  well-equipped  postmortem  room  has  a  book  for  recording  the 
data  obtained  at  postmortems.  This  book  is  usually  made  up  of 
printed  sheets,  having  a  heading  arranged  according  to  some  definite 
form  which  has  been  adopted  by  the  pathologist.  Such  headings  are 
useful  in  making  it  reasonably  certain  that  no  matter  who  makes  the 
postmortem,   the   customarv  'routine    will   be   followed.     The   volume 


TECHNIC. 


should  not  contain  a  very  large  number  of  pages,  certainly  not  over  four 
or  five  hundred,  as  a  large  number  would  make  it  too  bulky  for  con- 
venient handling;  nor  should  the  sheets  be  too  large.  The  book  to 
which  the  writer  is  accustomed  has  a  page  forty  centimeters  long  by 
twenty-eight  centimeters  wide,  and  has  printed  on  each  alternate 
page  the  form  given  at  the  foot  of  this  page.  At  the  time  the  book  is 
printed  it  is  well  to  have  two  or  three  hundred  sheets  left  unbound,  so 
that  at  postmortems  made  outside  the  institution  it  will  not  be  necessary 
to  carry  the  book. 

II.  PRELIMINARY  DATA. 

Before  beginning  the  postmortem  it  is  desirable  to  know  and  record 
the  name;  age;  residence,  or,  in  hospital  cases,  the  ward  and  bed;  sex; 
color;  date  and  hour  of  death;  date  and  hour  of  postmortem ;  methods 
of  preservation  if  any  have  been  used;  the  clinic  diagnosis;  the  name 
and  residence  of  the  physician,  if  any,  who  last  attended  the  case,  and, 
if  possible,  his  presence  should  be  had  at  the  postmortem. 

In  medicolegal  cases  the  body  should  be  identified.  If  the  time  at 
which  death  took  place  is  not  known,  it  may  be  approximated  by  the 
postmortem  evidences. 

III.  THE  POSTMORTEM. 

In  order  that  the  record  of  a  postmortem  may  be  perfect,  it  is  ab- 
solutely necessary  to  follow  a  definite  method  in  each  case.     If  circum- 


APPROVED  FORM  OF  POSTMORTEM  BLANK. 

[N.A.ME  OF  Institution.] 
POSTMORTEM. 

Ward Register  Xo 

Name,  Age,  and  Sex  of  Patient Color 

Physician.or  Surgeon Residence 

Resident   Physician Birthplace 


Date  and  Hour  of  Death '       Date  and  Hotir  of  Postmortem 


Clinical        \  Pathologic 

Diagnosis.  Diagnosis. 


When  possible,  it  is  desirable  that  the  following  order  of  examination  and  recording  the  postmortem  shall  be 
followed : 


T. 

External  examination: 

EWdence  of  injury. 

General  nutrition. 

Ante-  or  postmortem  mark 

IT 

Internal  examination. 

I.  .\bdominal  Wall. 

S.  Thymus;  Thyroid. 

14.  Pancreas. 

2.  Peritoneum. 

9.  Spleen. 

11;.  Intestines. 

3.  Pleurte. 

10.  Adrenals  and  Kidnevs. 

16.  Esophagus. 

4.  Pericardium. 

11.  Bladder  and  Internal  and  Ex- 

17. Vena  Cava  and  Aorta 

5.  Heart. 

ternal  Genitals. 

la.  Head. 

6.  Lungs. 

12.  Stomach  and  Duodenum. 

19.  Spinal  Cord. 

7.  Larynx;  Trachea;  Bronchi. 

13.  Liver. 

20.  Miscellaneous. 

POSTM  ( )  KT  E  M    K  X  A  M  I  N  A  T I O  \  S. 


stances  demand  a  variation  from  this  routine  method,  the  reason  for 
varyi)ti;  slioiilJ  constitute  a  part  of  the  record.  The  following  presents 
nothing  original,  and  is  the  method  adopted  by  the  writer: 

(A)  The  Date  and  Hour  of  the  Postmortem. 

(B)  External  Examination  of  the  Body. 

(a)  Is  the  body  dead.'  The  following  observations  should  be  made 
and  recorded  as  a  part  of  the  ]>ostmortem  notes,  as  they  cover  not  only 
the  signs  of  death,  but  constitute  a  part  of  the  evidence  of  diseased 
conditions:    (i)   Examine  for  evidence  of  respiration  and   circulation. 

(2)  Look  for  opacity  of  the  cornea,  loss  of  sensibility  in  the  conjunctiva, 
pupillarv  reaction,  which  may,  in  doubtful  cases,  be  tested  by  atropin  or 
eserin;  if  the  eves  are  sunken,  with  wrinkled  tunics,  the  evidence  is  clear. 

(3)  Pallor  of  the  body  may  or  may  not  be  present,  and  while  valuable 
as  a  sign  of  death,  it  may  be  found  in  the  living  during  swooning,  the 
algid  state  of  ague,  collapse,  etc.  (4)  Cooling  of  the  l)ody  to  the  tem- 
perature of  the  surrounding  medium  {cils^or  mortis)  occurs  in  from  fifteen 
to  twentv-four  hours.  The  bodies  of  children  and  old  and  lean  bodies 
cool  quite  rapidly,  while  bodies  of  fat.  young,  and  middle-aged  in- 
dividuals retain  the  heat  much  longer,  the  bodies  of  persons  dying 
from  suffocation,  electricity,  tetanus,  and  yellow  fever  very  slowly  yield 
their  heat.  (5)  Cadaveric  rigidity,  or  rigor  mortis,  occurs  at  a  varying 
interval  after  death.  It  may  become  manifest  but  a  few  minutes  after 
death,  or  it  may  be  delayed  eighteen  or  twenty  hours;  usually,  it 
develops  simultaneously  with  the  loss  of  body  heat.  The  duration  of 
rigor  mortis  is  extremely  variable,  lasting  in  some  instances  but  a  few 
moments;  in  other  cases,  hours,  days,  or  even  weeks.  (6)  Cadaveric 
lividitv  (the  cadaveric  blotches  called  livores  mortis)  and  siiggillation  are 
terms  applied  to  the  livid  or  violet-colored  discoloration  which  is  seen 
usuallv  several  hours  after  death.  It  ]:)ecomes  apparent  in  the  most 
dependent  portion  of  the  body,  and  is  the  result  of  blood  gravitating  into 
the  capillaries.  ( 7 )  Piitrcjacti'on  is  an  indubitable  sign  of  death.  The  time 
at  \vhich  it  becomes  manifest  varies  greatly,  and  is  dependent  upon  the 
condition  of  the  bod  v.  the  surrounding  media,  and  the  cause  of  death. 
(8)  Experimentallv.  'we  may  infer  that  the  body  before  us  is  dead  V)y 
injecting  ammonia  water  under  the  skin;  in  death  such  a  procedure 
leaves  no  mark,  but  in  simulated  death  it  occasions  a  deep  red  or  pun)le 
spot.  A  dead  body  can  not  be  blistered.  Brissemoret  and  Ambard 
state  that  aciditv  of  the  tissues  is  an  indubitable  sign  of  death.  Icard 
suggests  the  subcutaneous  injection  of  0.5  gm.  of  fluorescein  which,  if 
life  be  present,  rapidlv  stains  the  skin,  eyes,  mouth,  urine,  and  saliva. 
The  iodids  may  be  similarly  used  in  the  saliva  or  urine  exammed  for 
iodine. 

{b)  General  Considerations.— The  amount  of  adipose  tissue,  the 
muscular  development,  and  the  nutrition  of  the  body  should  be  carefully 
noted,  and  the  record  completed  or  verified  as  the  internal  examination 
proceeds.  In  case  the  body  has  not  been  identified  an  elaborate  des  • 
tion  should  be  made  for  the  purpose  of  further  identification :  the  hi-, 
weight,  measurement  of  chest,  limbs,  hands,  and  feet,  color  of  eyes  and 
hair  should  be  noted,  and  of  the  last  some  should  be  preserved. 
A  careful  survev  of  the  mouth  as  to  dental  peculiarities,  absence  ot 
teeth  filled  or  irregular  teeth,  or,  better,  a  dental  impression  taken 
in  w^ax  or  plaster,  should  be  made.     If  false  teeth  are  present,  they 


6  TECHNIC. 

should  be  removed  as  possible  aids  to  future  identification.  Abnor- 
malities, malformations,  marks  of  any  kind,  should  be  noted,  and, 
when  possible,  a  photograph  of  the  nude  body  should  be  obtained. 
Such  data  may,  with  perfect  propriety,  constitute  a  part  of  any  post- 
mortem record;  indeed,  they  are  desirable  although  rarely  incorporated 
in  the  protocol.  Except  in  the  cases  mentioned  they  might  have  little 
value  in  any  given  postmortem,  but  in  the  compilation  of  important 
data  based  of  necessity  on  a  large  number  of  cases — e.  g.,  the  size  and 
weight  of  organs  as  compared  with  the  height  and  weight  of  the  individ- 
ual— such  records  would  become  invaluable. 

(c)  Evidence  of  Violence  or  Disease. — Ecchynwses  should  be  carefully 
described  as  to  size,  shape,  and  position.  This  form  of  discoloration 
may  be  distinguished  from  sitggillaiion  in  that  it  does  not  disappear  on 
pressure,  and  if  an  incision  be  made  into  it,  bloody  fluid  will  escape,  or 
a  clot  may  be  discovered  in  the  subcutaneous  tissue.  All  abrasions, 
eruptions,  bed-sores,  ulcers,  cicatrices,  wounds,  edema,  pigmentations 
in  the  skin  and  mucous  membranes  must  be  accurately  described,  and 
their  positions  carefully  recorded.  Fractures  and  dislocations  must  be 
closely  observed,  and  their  character  and  the  parts  involved  described. 
The  external  orifices  of  the  body  should  be  examined,  and  their  condition 
and  contents  noted — e.  g.,  mouth  and  nose  for  foreign  bodies,  evidences 
of  corrosive  poisoning,  etc.;    in  the  female,  the  breasts,  abdomen,  and 


Fig.  2. — Modified  Virchow  Postmortem  Knife. 
Twenty-four  centimeters  long,  of  which  9.5  cm.  is  cutting-edge. 

external  genitals  should  be  examined  for  evidences  of  disease,  violence, 
or  physiologic  processes,  such  as  menstruation,  recent  delivery,  or 
evidences  of  past  gestation,  as  shown  by  the  mammae,  abdomen  (linea 
albicantes),  or  external  genitals ;  in  the  male  look  for  evidence  of  malfor- 
mation of  the  sexual  organs  or  venereal  disease,  also  seminal  stains. 
Examine  the  anus  for  fissures,  inflammation,  fistulae,  morbid  growths, 
cicatrices,  etc.     Examine  the  hernial  outlets  for  evidences  of  rupture. 

If  the  body  is  that  of  an  infant,  examine  the  fontanels  and  sutures,  and 
note  the  various  diameters  of  the  skull.  Measure  the  body  and  examine 
the  umbilical  cord.  In  the  male  the  scrotum  should  be  examined  to  de- 
termine if  the  testicles  have  descended;  note,  also,  the  presence  or 
absence  of  vernix  caseosa.  Carefully  examine  the  epiphyses,  and 
especially  that  of  the  lower  extremity  of  the  femur. 

(C)  Internal  Examination  of  the  Body. 

The  large  Virchow  knife  is  used  for  most  of  the  incisions ;  it  is  grasped 
firmly  in  the  hand  by  the  thumb,  middle,  ring-,  and  little  fingers,  while 
the  index-finger  rests  upon,  or  at  the  side  of,  the  blade.  Cuts  are  made 
with  a  drawing  movement,  the  shoulder-  and  elbow-joints  acting  as 
centers,  the  wrist  and  fingers  rigid.  Pushing  the  knife  through  a  tissue 
or  organ,  as  one  would  a  chisel,  is  to  be  avoided,  and  equally  objection- 
able are  sawing  and  hacking.  In  ordinary  dissection  a  scalpel  is  held 
like  a  pen,  motion  being  at  the  joints  of  the  fingers  and  wrist — a  process 


POSTMOkTH.M    EXAMIXATIONS.  7 

entirely  too  tiresome  and  slow  for  postmortem  work  except  when  very 
delicate  dissections  are  to  be  made. 

The  body  rests  firmly  upon  the  back,  and  the  operator,  if  right- 
handed,  stands  to  the  right  of  the  cadaver.  To  expose  the  abdominal 
and  thoracic  cavities,  an  incision  shoidd  be  carried  from  the  lower  border 
of  the  thyroid  cartilage,  or  from  the  interclavicular  notch,  to  the  sym- 
physis pubis,  making  a  sharp  semicircular  turn  to  the  left  at  the  umbilicus 
in  order  to  avoid  injury  to  the  remains  of  fetal  organs  at  that  j)oint.  The 
point  in  the  neck  at  which  to  begin  the  incision  will  be  determined  by 
circumstances  over  which  the  operator  commonly  has  no  control.  If 
he  can  select  the  starting-point  of  his  incision,  he  will  ordinarily  begin 
just  under  the  chin,  or  may  even  make  a  Y-shaped  cut  extending  to  the 
angle  of  the  jaw  on  either  side;  this  permits  a  most  careful  examination 
of  the  floor  of  the  mouth,  pharynx,  larynx,  and  adjacent  structures. 
So  extensive  a  dissection  is  rarely  permissil)le;  in  most  instances  the 
loosened  skin  can  be  retracted  upward  in  such  a  manner  as  to  permit  the 


J-      - ISION,  SHOUI.. .        .  ..;,..,„    ;iii,  .VuKuUlNAI.  Cavity. — {LttulU.) 

Ordinarily  it  is  not  possible  to  extend  the  incision  to  the  chin,  in  which  case  it  docs  not  go  beyond  the  interclavicular 

notch. 


removal  of  the  tongue  when  the  vertical  incision  does  not  rise  above  the 
level  of  the  thyroid  cartilage.  Still,  as  before  stated,  circumstances, 
more  commonly  than  any  arbitrary  rule,  will  settle  this  point. 

Over  the  abdomen,  the  first  incision  should  pass  through  the  skin  and 
subcutaneous  tissue;  then  carefully  cut  through  the  abdominal  wall 
immediately  below  the  ensiform  cartilage;  insert  two  fingers  of  the  left 
hand,  drawing  the  abdominal  wall  upward;  continue  the  incision,  the 
fingers  being  used  as  a  guide  to  the  knife.  A  most  excellent  rule,  never 
to  be  forgotten  by  the  beginner,  is  to  always  keep  the  point  of  the  knife 
in  view,  or,  if  this  is  not  possible,  it  should  be  guanled.  If  the  novice 
makes  it  a  rule  never  to  cut  anything  until  he  has  identified  it  and  de- 
termined what  are  its  relations,  using  touch  possibly  more  than  sight  to 
establish  these  facts,  he  will  often  be  astonished  at  the  dexterity  which 
he  quickly  acquires  and  the  rapidity  with  which  his  senses  become 
trained  to  recognize  the  tissues  before  him'.  Note  the  amount  and 
color  of  the  subcutaneous  fat  in  the  al)dominal  wall,  its  consistency,  and 


8 


TECHNIC. 


the  presence  or  absence  of  edema.  Examine  the  muscles  for  pallor, 
hyaline  spots,  degenerative  changes  (such  as  occur  in  typhoid  fever), 
and  small  white  ovoid  bodies,  encysted  trichinae.  Dissect  the  tissue 
from  the  chest-walls  as  far  back  as  the  junction  of  the  costal  cartilages 
with  the  ribs;  then  make  strong  traction  on  the  abdominal  walls  to 
break  up  the  rigor  mortis.     After   breaking  up  the  rigor  mortis  the 


Fig.  4. — The  Sternum,  Costal  Cartilages,  and  Articulation  of  the  Clavicle,  as  Exposed  after  Turn- 
ing Back  the  Soft  Parts. — (Modified  from  Virchow.) 

On  the  left  is  shown  the  line  of  incisions  made  through  the  cartilages  from  below  upward,  if  a  costotome  is  used; 
from  above  downward,  if  a  knife  or  saw  is  employed;  and  also  the  incision  necessary  for  disarticulating  the 
cla^^cle.  When  it  is  not  desirable  to  disarticulate  the  cla\-icle,  the  manubrium  is  separated  from  the  gladiolus 
at  point  A,  the  incision  being  made  from  behind. 

muscles  can  be  further  incised,  and  examined  for  evidences  of  bruises, 
inflammation,  and  suppuration,  and  suspicious  portions  removed  for 
microscopic  study. 

In  the  Paris  Morgue'  the  incision  used  begins  immediately  beneath 


*  Paris  letter  in  the  "Boston   Medical   and  Surgical  Journal,"  May  19, 

482. 


1S98, 


POSTMOUTKM    KXAMINATIDNS.  () 

the  chin,  jiasscs  over  the  larynx  and  trachea,  sweeps  across  nearly  to 
the  left  anterior  axillary  line,  which  is  followed  to  the  crest  of  the  pelvis. 
is  carried  alontj  the  up])er  anterior  border  of  the  j^elvis  to  the  ri^ht 
anterior  axillary  line,  thence  to  the  anterior  margin  of  the  ri^'ht  axilla, 
and  finally  to  the  startin<;^-point.  In  the  i)resence  of  sj)ecial  conditions 
such  an  incision  might  be  advanta.c;cous;  in  most  instances  it  is  clearly 
unnecessary. 

Abdominal  Cavity. — First  note  the  relative  position  and  color 
of  the  Hver.  stomach,  and  intestines;  and  also  the  relations  of  the 
viscera  to  the  costal  and  ensiform  cartilages.  The  examination  of  the 
cavity  is  not  of  the  organs  individually,  Imt  of  their  relation  to  one 
another  and  to  the  walls;  also  examine  the  serous  membrane— the 
peritoneum.  A  careful  search  should  be  made  for  adhesions  and 
other  evidences  of  inflammation,  recent  or  old,  and  for  thickening  and 
opacity  of  the  serous  membrane.  The  amount  and  character  of  anv 
fluid  in  the  cavity  must  be  noted,  and,  if  in  excess  or  otherwise  abnormal, 
the  source  or  cause  of  the  morbid  condition  must  be  sought.  The 
color  of  the  Hver  should  be  observed  before  those  changes  incident  to 
the  oxidation  of  the  blood  occur.     Search  carefully  for  perforations  of 


FiC.    S. — COSTOTOME. 


the  bowel,  stomach,  bladder,  or  gall-bladder,  whenever  the  fluid  in  the 
cavity  is  abnormal.  Note  accurately  the  position  of  the  diaphragm, 
ordinarily,  on  the  right  side  it  ascends  as  high  as  the  fourth  rib  or  inter- 
space; and  on  the  left,  to  the  fifth  rib.  Remove  any  fluid  present  in 
the  cavity  before  opening  the  thorax,  otherwise  fluids  in  the  abdomen 
flow  into  the  thoracic  cavity  and  thereby  complicate  the  examination. 

In  infants  the  umbilicus  must  be  examined  carefully;  the  attached 
cord  or  part  of  the  cord  and  the  fetal  vessels  should  be  closely  inspected 
and  fully  descrilied;  so  far  as  i)Ossil)Ie.  the  vessels  should  be  examined  for 
evidences  of  infection,  throml)Osis,  ami  obliteration. 

Thoracic  Cavity. — In  the  new-born  when  it  is  imi)ortant  to 
determine  if  resjnration  had  been  established  or  if  air  had  entered  the 
lung  it  is  well  to  ligate  the  trachea  as  soon  as  the  first  incision  is  made 
and  before  op>ening  the  abdominal  cavity;  such  precaution  prevents  air 
from  being  drawn  into  the  lungs  by  traction  on  the  diaphragm  or  raising 
the  breastplate.     With  a  heavy  knife,  or  costotome  (or.  in  tlv      '  e 

of  the  latter,  when  the  cartilages  are  calcareous,  a  saw  may  be  u  r 

the  costal  cartilages  close  to  the  ribs,  care  being  exercised  not  lu  i:ijure 


lO 


TECHNIC. 


the  tissues  beneath.  If  the  costotome  is  used,  the  blade  inserted  be- 
neath the  cartilage  should  be  made  to  hug  that  structure  closely;  if  a 
knife  or  saw  takes  the  place  of  the  costotome,  the  incision  through  the 
cartilages  should  begin  above,  and  before  one  cartilage  is  completely 
severed,  the  blade  or  shank  of  the  instrument  should  be  made  to  rest 
on  the  next  cartilage,  thus  preventing  sudden  thrusts  which  may  wound 
underlying  structures.  When  the  last  cartilage  is  reached,  it  should  be 
gently  raised  by  the  unoccupied  hand,  at  the  same  time  depressing  the 
underlying  structure,  thereby  avoiding  the  danger  of  wounding  the 
latter. 

Divide  the  attachment  of  the  diaphragm,  raise  the  sternum,  and 
dissect  off  the  attached  tissue,  taking  care  to  direct  the  edge  of  the  knife 
toward  the  bone  in  order  to  avoid  injury  to  the  pericardium  or  other 
intrathoracic  tissues.  Cut  the  ligaments  binding  the  clavicle  to  the 
sternum,  divide  the  sternal  attachment  of  the  sternocleidomastoid 
muscle,  and  pull  the  breastplate  to  one  side.  In  a  cadaver  in  which 
the  section  of  the  thorax  has  been  made  as  just  directed,  the  shoulders, 
having  lost  the  support  of  the  clavicle  through  their  sternal  attachment, 
collapse  together,  making  the  chest  appear  very  much  distorted.  To 
avoid  this,  in  cases  where  the  body  is  to  be  viewed,  the  manubrium  and 
gladiolus  may  be  disjointed  by  drawing  the  edge  of  the  knife  across  the 
under  surface  of  the  articulation  of  the  manubrium  and  gladiolus  (see 
Fig.  4,  p.  25)  and  raising  the  lower  segment  of  the  sternum. 


Fig.  6.— Saw. 
A  large  firm  handle  is  wanted,  with  good  pistol  grip. 

Examine  the  pleurse  for  evidences  of  inflammation,  either  remote 
or  recent;  note  presence  or  absence  of  fluid,  also  its  quantity  and  char- 
acter, as  in  the  peritoneum.  Fluid  in  each  pleura  should  be  removed, 
so  as  to  prevent  its  flowing  into  the  pericardium;  or,  in  case  the  peri- 
cardium contains  much  fluid  and  any  escape  into  the  pleura,  its  quantity 
may  be  accurately  estimated.  The  fluid  in  each  cavity  should  be 
measured,  and  the  quantity  made  a  part  of  the  record.  Adhesions 
should  be  looked  for  and  described.  The  mediastinal  tissues,  the  re- 
lation of  cysts,  new  growths,  and  aneurysms  to  adjacent  viscera,  and 
also  the  thymus  may  now  be  investigated.  The  last-named  structure 
atrophies  in  childhood,  but  in  infancy  is  an  organ  that  should  always 
be  examined.  The  pericardium  should  now  be  opened  by  an  incision 
extending  from  base  to  apex  in  a  line  parallel  to  the  long  axis  of  the 
heart.  In  opening  the  pericardium  the  writer  has  seen  the  heart  in- 
jured so  often  that  he  desires  to  insert  a  word  of  caution  and  give  a 
little  more  detailed  method  for  preventing  this  accident.  The  peri- 
cardium is  picked  up  in  a  fold  either  by  the  index-  and  fore-finger  of 
the  left  hand  or  by  the  use  of  "rat-toothed"  forceps;  b}^  gentle  trac- 
tion this  fold  of  the  pericardium  can  be  raised  to  a  distance  of  2.5  cm. 
The   back  of  the  knife  is  now  placed  against  the  heart  and  the  fold, 


1  •  ( » S T  .\ K)  K  r  !•  M    i:  X  A  M  I  N  A  T I O N  S . 


I  I 


made  as  previously  directed,  is  iranslixcd  and  the  opening'  completed 
by  cutting  from  within  outward.  A  similar  incision  lias  been  long 
recommended  by  surgeons  while  operating  upon  hernia  where  wound- 
ing the  imderlying  tissue  may  be  attended  liy  calamitous  conse(}uences, 
and  if  applied  to  the  pericardium  with  Ijut  slight  precaution,  wound- 
ing of  the  heart  may  be  entirely  avoided.  From  this  incision,  which 
is  two  or  three  centimeters  in  length,  the  incision  in  the  long'^axis  of 
the  heart,  as  previously  directed,  may  be  readily  made.      Incisions  at 


Fic.  7.— Heart  SHOwnxc.  the  Lines  for  Inosions  in  the  Preliminary  Examination  and  Final  Section. 
Fully  Exposing  the  Valvk. — (A/trr  \'inho-u.) 

A.  Pulmonary  artery.  B.  .Aorta.  C.  Right  auricle.  The  incision  .V  to  iV  is  th.it  adrised  by  Virchow.  The 
one  preferred  by  the  writer  is  from  K  to  /,  for  ihe  preliminar)-  opening  .  f  tlir  rikilit  vintrii  1<-.  Th.  firrliminarf 
operiinK  of  the  right  auricle  is  made  at  C.     The  prflimin.-iry  open:  'h.- 

prclimin;ir>'  opening  of  ihi-  left  ventricle  is  m.vlc  at  F  to  E.     .■\lter  it 

C  is  carried  out  through  ihc  vena,  cava;   ihr  in.  i-i.n  fr.:;!  K  '<•  I  ^  « 

twecn  the  letters  .U  an^i  .!.  and  l>eIo\v  is  ■  ir 


incision  F  to  £.  in  the  lift  ventricle,  is 
aorta  at  L.     From  the  lower  [xinion.  at  / 
this  permits  the  flap  to  be  turned  back  so  lii 
be  carried  through  the  mitral  orifice. 


1 1-1. .n  iii.ili-  r.i.iy  (den 


right  angles  to 
writer  does  not 
cision  than  that 
the  great  vessels, 
of  inflammation, 
the  great   blood- 
character. 

The  Heart. — Xote  the  condition  of  contraction  or  relaxation  of  the 


the  long  incision  are  rarely,  if  ever,  demanded;    the 

recall  an  instance  in  which  he  has  needed  a  larger  in- 

aflforded  by  the  opening  extending  from  the  apex  to 

Examine  the  layers  of  the  jjericardium  for  evidences 

and  look  carefully  for  adhesions,  particularly  about 

l-vessels.     Measure   the  pericardial   fluid   and   note  its 


12  TECHNIC. 

heart's  wall;  open  the  heart  in  situ;  raise  the  organ  by  its  apex,  pass 
the  fingers  of  the  left  hand  under  the  organ,  and  so  grasp  it  that  the 
thumb  and  first  finger  will  close  the  auriculoventricular  orifice  of  the 
right  side,  and  then  make  an  incision  into  the  auricle  between  the 
venas  cavas.  Examine  and  note  character  of  contents;  without  re- 
laxing the  grasp  on  the  auriculoventricular  orifice,  open  the  right  ven- 
tricle by  an  incision  in  line  with  the  pulmonary  artery  and  close  to 
the  ventricular  septum;  insert  the  index-finger  of  the  right  hand  and 
examine  the  contents.  The  left  heart  is  opened  by  grasping  it  as  in 
opening  the  right.  The  auricle  is  incised  near  the  appendix  and  im- 
mediately above  the  auriculoventricular  septum,  and  its  contents  are 
noted.     The  left  ventricle  is  opened  by  an  incision  almost  parallel  to 


Fig.  8. — Heart  Showing  the  Interior  of  the  Right  Ventricle  .and  Pulmonary  Artery. — (After  Virchow.) 
If  the  incision  M  to  /,  figure  6,  be  made  as  advised  by  the  writer,  the  papillary  muscle  (.4)  ^vilI  be  carried  over  with 
the  ventricular  wall  (B),  thereby  better  exposing  the  auriculoventricular  orifice. 


the  opening  made  in  the  right  ventricle,  but  on  the  opposite  side  of 
the  septum,  and  the  incision  is  directed  toward  the  aorta.  The  pres- 
ence or  absence  of  blood  or  clots  in  the  left  ventricle  must  be  carefully 
noted.  Examine  the  great  vessels  as  to  abnormality,  aneurysm,  or 
other  disease  discernible  externally;  gross  lesions  involving  the  large 
vessel  trunks,  congenital  defects,  and  the  presence  of  thrombi  or  em- 
boli had  best  be  determined  before  the  heart  is  removed;  and  if  pres- 
ent, it  may  be  expedient  to  complete  the  dissection  before  removing  the 
organ.  The  heart,  whether  normal  or  not,  should  never  be  severed 
from  abnormal  or  diseased  vessels  when  the  morbid  condition  is  likelv 
to  have  materially  influenced  the  organ;  this  is  especially  true  of  mal- 
formations and  aneurvsms.     When  the  relation  of  abnormalitv  of  the 


I'OSTMOKTKM    i:  \  A  M  I  NATloXS.  I  5 

intrathoracic  vascular  system  to  the  air-passaj,'cs  or  lun^^s  is  importaiU. 
Letulle's  method,  mentioned  below,  should  he  followed.  In  the  new- 
born it  may  be  advisable  at  this  time  to  trace  the  pulmonary  artery 
and  aorta,  demonstrating  the  relation  of  one  to  the  other,  and  the 
condition  of  the  ductus  arteriosus.  Remove  the  heart,  dividing  the 
great  vessels  from  below  upward,  severing  the  aorta  last.  Test  the 
valves  as  to  competency,  being  sure  to  wash  out  all  clots  before  mak- 
ing the  test.  Enlarge  the  incisions  already  made  so  as  to  be  able  to 
examine  the  endocardium  in  detail.  Carry  the  incision  in  the  right 
auricle  out  through  the  two  cavc-c;    prolong  the  incision  in  the  rii'ht 


Fig.  9. — Heart  with  the  Left  Ventricle  Laid  Open,  Showing  the  Aortic  Ccsps  and  the  Vcntricvlab 
.Aspect  of  the  Mitral  Valve.— (^//<t  Virchou.) 
The  Icllcrs  have  the  same  significance  a.s  in  figure  7. 


ventricle  through  the  pulmonary  artery  and  the  incision  in  the  left 
ventricle  through  the  aorta.  The  left  auricle  is  opened  by  continuing 
the  incision  already  made  into  the  pulmonary  vein.  Note  any  veg- 
etations on  the  valves,  thickenings  or  opacity  of  the  endocardium; 
examine  closely  the  condition  of  the  foramen  ovale.  State  the  gen- 
eral appearance  of  the  cardiac  muscle. 

Measuring  the  Orifices:  Graduated  cones,  balls  of  different  sizes. 
and  other  devices  for  measuring  the  cardiac  orifices  can  be  purchased 
and  bv  some  are  recommended;    I  have  never  held  them  in  favor,  as 


14 


TECHNIC. 


the  question  of  how  much  force  may  be  used,  or  exactly  where  the 
reading  is  to  be  taken,  can  not  be  accurately  answered;  if  the  wall 
of  an  orifice  be  dense  and  unyielding — which  normally  it  never  is — such 
appliances  might  be  of  use.  Ordinarily  it  is  best  to  open  the  orifice 
and,  without  any  lateral  stress,  lay  a  flexible  tape  over  the  exposed 
line;  when  such  a  tape  is  not  available,  a  string,  or  better  a  wire,  may 
be  used  and  later  measured ;  the  circumference  so  obtained  may  readily 
be  converted  into  diameter  by  dividing  by  3.14. 

Examine  coronary  arteries  by  passing  a  director  into  each  in  turn, 
and,  with  knife  or  scissors,  opening  the  artery  as  far  as  possible.  Probe- 
pointed  scissors  may  be  used  to  advantage,  and  if  the  probe-pointed 
blade  is  small,  the  arteries  may  be  opened  even  to  their  smaller  branches. 
Weigh  the  heart. 

Both  lungs  may  be  removed  at  once.  Adhesions  must  be  carefully 
broken  up;    this  can  usually  be  accomplished  by  the  fingers  alone; 

occasionally,  however,  the 
knife  or  scissors  (prefera- 
bly the  latter)  w411  be 
necessary;  when  the  ad- 
hesions are  very  dense  or 
extensive,  the  costal  pleura 
may  be  separated  from  the 
ribs  and  intercostal  mus- 
cles. If  the  organs  are 
adherent  to  the  dia- 
phragm, it  is  best  to 
detach  the  latter  from 
the  ribs  and  remove  it 
with  the  lung;  often  only 
a  patch  will  require  re- 
moval, at  other  times  the 
entire  diaphragmatic 
pleura  may  be  adherent. 
Incise  the  great  vessels 
as  they  pass  out  of  the 
thorax;  cut  through  the 
trachea,  being  careful  not 
to  injure  the  esophagus. 
Gentle  protracted  traction  will  strip  the  organs  from  the  tissue  behind, 
bringing  forward  with  the  pericardium  the  aorta,  which  must  be  severed 
at  the  diaphragm.  If  it  is  desired  to  leave  the  aorta,  this  can  easily  be  done 
by  separating  it  from  the  pericardial  attachments  before  delivering  the 
lungs.  When  removed  singly,  the  left  lung  is  removed  first;  loosen  all 
adhesions,  pull  the  apex  downward  and  the  remainder  forward,  cutting 
the  bronchi  and  vessels  from  behind;  some  workers  prefer  an  anterior 
incision;  probably  the  height  of  the  operator  or  of  the  table  leads  to 
different  methods  and  may  influence  the  selection  made  by  the  beginner. 
Note  the  quality  and  quantity  of  any  fluid  flowing  from  the  severed 
bronchus.  Note  the  general  appearance,  color,  and  condition  of  the 
lung.  Examine  for  crepitation,  allowing  the  borders  and  margins  to 
slip  gently  between  the  fingers  and  thumb;  avoid  force.  At  this  time 
lav  the  lung  on  a  solid  surface,  preferably  slate  or  stone,  or  on  one  of  the 


Fig.  10. — Scissors. 
Those  shown  in  the  upper  cut  will  be  most  useful,  particularly  if  the 
blade  shown  in  the  cut  as  having  the  sharper  point  be  slightly 
probe-pointed. 


POSTMORTEM    EXAMINATIONS. 


»s 


limbs  of  the  cadaver,  to  avoid  any  sounding-board  inlluence,  and  care- 
fully percuss  the  organ,  comparing  the  result  of  ])ercussion  with  the 
sensations  elicited  by  palpation.  The  incisions  made  in  the  lung  should 
be  conspicuous  by  reason  of  their  length,  and  the  longer,  other  things 
being  equal,  the  better.  To  accomplish  this,  it  is  best  to  use  a  long 
section  knife  (Fig.  14),  which  should  be  exceptionally  sharp,  making  an 
incision  from  apex  to  base,  extending  through  all  the  lobes  in  a  line 
corresponding,  as  nearly  as  possible,  to  the  axillary  aspect  of  the  organ. 
Lay  open  and  dissect  down  the  bronchi,  and  carefully  examine  their 
condition,  a  sharp  lookout  being  maintained  for  the  presence  of  foreign 
bodies.  The  branches  of  the  pulmonary  vessels  should  be  examined  for 
thrombi,  emboli,  and  the  presence  of  sclerosis.  Note  the  appearance 
of  the  peribronchial  glands.     Weigh  each  lung  separatelv. 

Larynx,  Trachea.  Bronchi,  and  Thyroid  Gland. — The  examination 
of  these  structures  is  usually  best  accomplished  after  their  removal  en 
masse,  together  with  the  contents  of  the  floor  of  the  mouth  and  the 
pharyngeal  wall.  If  the  primary  incision  w^as  carried  to  the  chin  the 
organs  may  easily  be  extracted;  on  the  other  hand,  if  they  must  be 
removed  subcutaneously,  considerable  difficulty  will  be  encountered. 
The  skin  must  be  carefully  dissected  from  the  underlying  tissues,  and  a 
long-bladed  knife  passed  from  below  upward,  entering  the  floor  of  the 
mouth  as  far  anteriorly  as  possible,  making  an  incision  laterally  on  both 


Fig.  II. — Grooved  Director. 
Useful  for  opening  arteries,  tracing  sinuses,  ducts,  etc. 


sides  along  the  rami  of  the  lower  jaw.  The  mouth  is  then  opened 
widely,  and  the  incision  carried  backward  and  upward,  detaching  the 
soft  palate  from  the  hard  palate,  and  at  the  same  time  freeing  the  tonsils. 
The  removal  of  this  mass  is  accomplished  by  pulling  the  esophagus  and 
larynx  downward,  pushing  a  long-bladed  knife  up  behind  the  esophagus, 
and  severing  posteriorly  and  laterally  the  pharyngeal  wall  as  high  as 
possible.  After  removal  the  esophagus  may  be  dissected  from  the 
larynx,  and  examined  later,  with  or  after  the  stomach,  or  it  may  be  at 
once  severed  near  the  diaphragmatic  opening,  a  ligature  being  applied  to 
prevent  the  escape  of  the  stomach-contents.  If  removed  with  the  ad- 
jacent structures,  it  is  opened  on  the  posterior  aspect,  the  lar^-nx  and 
trachea  being  opened  anteriorly. 

Abdominal  Viscer.\. — The  spleen  is  now  removed.  This  is  ac- 
complished by  gently  lifting  the  organ  out  of  its  normal  bed,  pulling  it 
forward,  and  severing  the  blood-vessels  close  to  the  hilum.  As  a  result 
of  past  peritoneal  inflammation,  diaphragmatic  pleurisy,  or  inflammation 
of  some  adjacent  viscus  or  tissue,  as  the  colon  or  perirenal  structures,  the 
spleen  may  be  anchored  by  firm  adhesions  of  its  capsule  to  contiguous 
viscera.  Under  such  circumstances  it  is  best  to  dissect  the  organ  out 
with  very  great  care,  as  protracted  or  violent  traction  may  rupture  the 
thin  capsule;  and  if  it  be  softened  as  a  result' of  infectious  diseases  or 
other  cause,  the  entire  splenic  pulp  may  be  forced  through  a  compara- 


i6 


TECHNIC. 


tively  small  opening  in  the  capsule  of  the  organ.  Its  general  appear- 
ance described,  make  one  long  incision  through  the  convexity  extending 
down  to  the  hilum.  Note  color  and  consistency  of  parenchyma,  promi- 
nence of  the  Malpighian  bodies,  and  stroma.     Weigh  the  organ. 

TJic  Kidneys. — Ascertain  whether  both  are  in  their  normal  positions, 
if  possible.  The  left  suprarenal  body  and  left  kidney  are  next  examined. 
As  a  rule,  the  adrenal  and  corresponding  kidney  may  be  removed 
together.  This  can  readily  be  done  by  incising  or  tearing  the  peritoneum 
along  the  upper  and  posterior  border  of  the  kidney  and  gently  dissecting 

with  the  fingers  the  connective 
tissue    holding    the    adrenal    in 
'■^  place.      Raise  the  kidney  from 

its  normal  position,  note  con- 
dition of  blood-vessels  and  in- 
cise them;  examine  ureter  and 
sever  it.  With  very  little  effort 
the  ureter  may  be  traced  down- 
ward to  the  bladder.  This  should 
be  done  before  severing  the 
kidney,  as  later  it  may  be  quite 
impossible  to  demonstrate  that 
the  canal  contained  no  obstruc- 
tion. The  perirenal  fat  should 
be  carefully  removed  from  the 
kidney  and  the  surface  of  its 
capsule  accurately  described  be- 
fore incising  it.  Hold  the  kid- 
ney in  the  left  hand,  with  the 
pelvis  directed  toward  the  palm, 
and  with  one  sweep  of  a  sharp 
knife  incise,  from  the  cortex  to 
the  pelvis,  in  the  long  axis  of 
the  organ.  On  section,  note 
consistency,  color,  the  relative 
proportion  of  cortex  and  pyra- 
mid (normal  cortex  equals  one- 
half  the  p3'ramid) ;  the  condition 
of  capsule,  whether  thickened, 
tense  or  flaccid,  or  adherent  to 
cortex;  also  note  appearance  of 
stripped  surface  of  cortex, 
whether  smooth  or  rough,  etc. 
Examine  pelvis  of  kidney,  and 
weigh  the  organ.  The  same  process  is  repeated  upon  the  opposite  side. 
Examine  bladder  and  internal  genitals.  The  technic  of  this  exami- 
nation depends  largely  upon  the  conditions  present.  When  the  exami- 
nation of  the  upper  urinary  tract  (kidney  and  ureter)  has  led  to  any 
suspicion  of  disease,  it  is  best  not  to  detach  the  kidney  from  the  ureter 
or  ureter  from  the  bladder  until  the  examination  has  been  completed. 
The  examination  of  the  pelvic  viscera  can  usualh^  best  be  accomplished 
after  evisceration  of  the  pelvis.  It  is  best,  however,  to  open  the  bladder 
and  examine  its  contents  before  eviscerating,  and  in  the  female,  when 


Fig.  12. — Line  of  Incision  through  the  Posterior 
Border  of  the  Lung. — (Letulle.) 
This  cut,  following  the  line  from  x  to  y,  should  extend   to 
the  hilum.     The  surfaces  exposed   by  the    foregoing 
method  are  further  incised  at  short  intervals. 


POSTMOKTKM    KXA  M  1  NATIONS. 


there  is  any  ([uestioii  ot  criminal  almrtion,  a  thor(>ujT;h  examination  siiould 
be  made  l)y  finger  and  speculum,  using  no  tutting  or  pn^he-pfjintcd 
instrument  of  any  kind  until  wounds  have  been  excluded — as  far  as 
it  is  possible — before  the  examination  is  completed.  Evisceration  of 
the  pelvis  is  best  accomplished  by  an  incision  anteriorly,  under  the  jiubic 
arch,  hugging  the  true  pelvis  posteriorly,  and  removing  the  rectum  with 
the  other  contents  of  the  pelvis.  The  testicle  may  be  removed  without 
any  external  incision  in  the  scrotum  by  simply  dissecting  the  skin 
anteriorly  from  the  pubes  and  pulling  the  testicle  by  the  spermatic  cord 
gently  up  into  the  wound,  from  which  it  may  be  removed,  if  necessary 
dissecting  the  cord  around  to  the  seminal  vesicles.  The  ])enis  may  be 
simply  retracted  through  the  floor  of  the  pelvis,  and  rcmf)ved  with  the 
l^rostate  and  bladder. 

The  removal  of  these  organs  without  the  full  consent  of  the  de- 
ceased's family  should  never  be  made,  as  the  e.xcision  of  the  genital 
organs  is  always  looked  upon 
as  having  been  done  merely 
to  gratify  morbid  curiosity, 
and  exactly  why  it  is  always 
discovered  seems  very  hard 
to  determine;  the  fact  re- 
mains that  the  uninitiated 
have  been  severely  censured 
for  the  removal  of  the 
external  genitalia,  even  in 
cases  where  it  was  perfectly 
justified  by  the  findings  and 
where  it  was  necessary  to 
exclude  other  possibilities. 

The  rectum  should  be 
dissected  from  the  posterior 
wall  of  the  bladder  in  order 
to  expose  the  prostate  and 
seminal  vesicles.  In  the  fe- 
male, as  this  is  not  necessary, 
the  rectum  is  opened  on  its 
posterior  aspect,  the  vagina 
laterally,  and  the  urethra  and 

bladder  anteriorly,  thus  permitting  all  the  parts  to  be  restored  to  their 
normal  relation  with  each  other.  The  opening  on  the  lateral  aspect  of  the 
vagina  is  carried  anteriorly  at  the  upper  end  and  continued  through  the 
anterior  wall  of  the  cervix  and  body  of  the  uterus.  If  urine  be  present 
in  the  bladder,  its  character  and  quantity  shoidd  be  noted,  and  it  should 
be  preserved  for  future  examination. 

The  left  semilunar  ganglion  is  examined,  and  any  firmness  or  in- 
flammatory signs  noted.  The  ganglion  should  be  preserved  for  micro- 
scopic examination.  The  corresjjonding  organ  of  the  right  side  is  next 
in  order  of  examination. 

The  Sto}uacli  ami  DnoJcituiii. — In  cases  where  poisoning  is  suspected, 
ligatures  are  applied  at  the  cardiac  extremity  of  the  stomach  and  the 
upper  end  of  the  duodenum,  and  the  organ  removed:  in  order  that 
the  contents  may  be  carefully  examined,  the  stomach,  without  open- 


13. — I.NcisioN  FOR  Separating  the  Oral  a.vd  Pharyn- 
oEAi,   Structures   from  the  Ft.oor  of  the  .Mouth. — 

(Lfliillr.) 


1 8  TECHNIC. 

ing,  should  be  placed  in  a  clean  jar  and  sent  to  the  chemist.  In  case 
it  is  decided  to  open  the  duodenum  and  stomach  iti  situ,  as  is  best 
when  the  question  of  poisoning  does  not  enter  into  the  case,  make 
an  incision  along  the  anterior  surface  of  the  duodenum  and  greater 
curvature  of  the  stomach.  Examine  contents,  condition,  and  appear- 
ance of  mucous  membrane.  Foreign  bodies  are  frequently  met  with 
in  the  stomach.  Determine  if  the  bile-duct  is  patulous  by  pressing 
upon  the  gall-bladder  and  watching  for  the  escape  of  bile.  In  case 
this  simple  procedure  does  not  reveal  the  presence  of  the  ampulla  and 


Fig.  14. — Long,  Thin,  Brain  Knife,  of  Value  for  Incising  Organs. 
Originally  designed  for  brain  dissection,  but  at  present  used  for  incising  kidney,  liver,  spleen,  tumors,  etc.     As 
shown  in  the  illustration,  the  instrument  should  not  have  a  cutting-edge  measuring  less  than  sixteen  centi- 
meters.    The  graduation  along  the  back  of  the  knife  affords  a  convenient  measure.     On  the  other  side  the 
graduation  is  in  inches. 

demonstrate  that  the  cystic  and  common  ducts  are  patulous  they 
should  be  carefully  exposed.  This  can  not  be  done  after  the  removal 
of  the  pancreas,  duodenum,  or  liver;  as  it  is  important  in  many,  if 
not  all,  cases  to  assure  one's  self  of  thfe  condition  of  the  hepatic,  cystic, 
and  common  ducts,  and  as  cutting  through  either  of  them  may  render 
later  demonstration  unsatisfactory  or  even  quite  impossible,  they  should, 
therefore,  be  dissected  out  in  situ.  Open  the  ductus  cominunis  choled- 
ochus,  examine  mucous  membrane,  and  continue  the  incision  upward 
into  the  gall-bladder  and  larger  hepatic  ducts. 


Fig.  15. — Enterotoile. 
Useful  for  opening  stomach,  duodenum,  intestines,  etc.     Not  uncommonly  the  blunt-pointed  lower  blade  is  so 
made  that  it  forms  a  tooth,  like  the  barb  on  a  fish-hook,  and  when  introduced,  can  not  be  withdrawn.     Such 
hook-pointed  enterotomes  are  to  be  avoided. 


The  portal  vein,  hepatic  vein,  and  vena  cava  may  be  opened  be- 
fore the  removal  of  the  liver;  or,  as  the  first  two  must  be  severed  dur- 
ing the  removal  of  the  organ,  they  may  be  examined  at  that  time.  The 
condition  of  their  contents  and  appearances  of  their  walls  must  be 
noted. 

The  liver  may  now  be  detached  from  the  diaphragm,  or,  if  it  is 
adherent  to  that  structure,  the  two  may  be  removed  together;  when 
the  lung,  liver,  and  diaphragm  are  fused  by  adhesions  at  their  points 
of  contact,  and  when  there  may  be  any  suspicion  of  a  suppurative 
lesion  burrowing  in  either  direction,  it  is  best  to  let  the  lung  remain 


POSTMOUTHM    ICXAM  I  \ATl0.\  S. 

in  sitit  until  the  i)roper  time  tor  examining  the  liver,  when  uir  iiim( 
structures  can  be  removed  together;  neither  the  lung  nor  the  liver 
should  be  sacrificed,  but  only  that  part  of  the  diaphragm  immediately 
involved  need  be  removed  with  the  attached  viscera.  The  shape  and 
color  of  the  liver  and  any  deformities  of  the  lobes  should  be  noticed, 
the  anterior  margin  examined,  and  its  condition  recorded.  The  inci- 
sion made  to  disclose  the  interior  of  the  liver  should  lie  a  long,  sweep- 
ing cut,  on  the  superior  aspect  of  the  organ,  extending  through  the 
longest  axis,  including  both  right  and  left  lobes  and  sufficiently  deep 
to  permit  the  folding  of  the  two  parts  without  tearing  the  narrow  banrl 
of  tissue  holding  them  together  on  the  inferior  surface  of  the  organ. 
On  section,  the  firmness  or  resistance  should  be  noted;  also  the  color, 
whether  uniform  or  mottled,  and  whether  or  not  bile  staining  be  pres- 
ent.    Weigh  the  organ. 

Pancreas. — At  the  time  the  bile-passages  are  opened  down  to  and 
through  the  ampulla,  it  is  well  to  seek  the  duct  of  Wirsung.  and,  if 
possible,  the  extension  into  the  pancreas:  accessory  ducts  should  be 
sought.  As  the  head  of  the  pancreas  is  dissected  from  the  duodenum 
a  careful  lookout  should  be  maintained  for  any  additional,  as  well  as 
normal,  ducts.  Separation  of  the  pancreas  from  the  duodenum,  which 
it  occasionally  envelops,  is  often  extremely  tedious.  Aberrant  pan- 
creatic tissue  should  be  sought  in  the  stomach,  duodenum,  and  jejunum. 
The  tail  and  most  of  the  l)ody  of  the  pancreas  may  be  detached  and 


1  K..    10. —  l'KUllt>. 

These  should  be  at  least  fifteen  or  twenty  centimeters  long.     One  should  be  very  slender. 

transversely  incised  partly  through,  at  short  intervals  (i  to  2  cm.), 
beginning  at  the  splenic  end.  Careful  inspection  of  the  surface  ex- 
posed at  each  incision  commonly  discloses  the  larger  duct  about  the 
junction  of  the  body  and  head  of  the  organ.  As  soon  as  recognized 
It  may  be  explored  by  a  fine  probe  and  finally  opened. 

The  csophagns  should  next  be  examined. 

Jntcstincs. — A  better  view  of  the  other  organs  and  greater  working 
room  are  afforded  by  removing  the  intestines  immediately  after  the 
spleen.  The  rectum  is  ligated  just  below  the  sigmoid  and  the  latter 
separated  by  incising  the  mesosigmoid  close  to  the  bowel.  The  pres- 
ence or  absence  of  renal  mobility  should  be  detennined,  after  which 
the  colon,  descending,  transverse,  and  ascending,  is  detached  in  the 
order  named.  The  caput  coli  is  raised  from  its  bed,  the  appendix  de- 
tached from  any  adhesions,  and  removal  of  the  small  intestine  con- 
tinued by  sectioning  the  mesentery  as  close  as  possible  to  the  gut.  As 
the  different  parts  of  the  ileum  come  in  view  any  abnormalit\  in  color, 
evidence  of  inflammation,  dilatation,  or  narrowing  should  lead  to  a 
closer  examination  of  the  mesentery,  which  ordinarily  is  inspect*^'!  ■» 
this  time.  While  dividing  the  mesentery  watch  for  enlarged  g! 
cysts  (chylous),  tumors,  thrombosed  vessels,  fat  necrosis,  etc.  Vv  n.  u 
the  blood  or  chylous  vessels  are  abnormal,  it  may  be  well  to  remove 
these  with,  and  leave  them  attached  to,  the  intestine.     Should  thrombi. 


TECHNIC. 


or  other  lesions  involving  the  vessels,  be  disclosed,  the  veins  and  ar- 
teries should  be  dissected  to  the  main  trunks,  and  if  possible  the  cause, 
if  local,  determined  before  going  further.  Any  lesion  located  in  the 
mesentery'  and  influencing  the  intestine  should  be  traced  with  that 
structure  to  which  it  had  best  be  left  attached.  The  gut  should  be 
carefully  opened,  and  the  contents  examined  as  the  incision  in  its  wall 
is  gradually  extended.  After  the  incision  made  by  the  enterotome 
has  been  concluded  the  mucous  surface  should  be  gently  washed  by 

a  slowly  flowing  stream 
of  water,  and  examined 
for  inflammation,  ulcers, 
cicatrices,  perforations, 
constrictions,  etc.  It  is 
best  to  open  the  intestine 
before  washing  it  out,  in 
order  more  accurately  to 
determine  the  contents,  ex- 
amine for  animal  parasites, 
locate  foreign  bodies,  etc., 
but  cleanliness  and  con- 
venience often  lead  'to  an 
unwise  reversal  of  the 
proper  order.  In  cases  of  suspected  poisoning  the  unopened  intes- 
tine should  be  sent,  in  a  clean  jar,  to  the  chemist. 

The  thoracic  duct  should  now  be  traced,  and  the  retroperitoneal  glands 
and  rcceptacidum  chyli  examined. 

The  aorta  and  its  branches  may  now  be  examined  in  detail. 
The  Head.^ — Insert   the   scalpel,  with  its    back  toward   the  skull, 
just  behind  one  ear,  and  carry  an  incision  across  the  vertex,  cutting  from 
within  outward.    If  the  knife  is  not  too  sharp,  the  hair  may  be  parted  and 


Fu;.   17. — Dissecting  Forceps. 
One  of  these  should  be  toothed.     These  will  be  needed  in  the  finer 
dissections,  as  in  tracing  the  hepatic  duct,  portal  vein,  and  re- 
ceptaculum  chyli. 


Fia.  18. — Mallet  or  Hammer. 


thrown  backward  and  forward  as  the  hand  and  knife  are  withdrawn. 
The  incision  should  be  far  enough  back  to  be  invisible  from  the  front 
when  closed.  The  scalp  is  reflected  forward  and  backward  from  this 
incision  as  low  as  the  superciliary  ridge  in  front  and  the  occipital  pro- 
tuberance behind. 

In    many    cases    great  care   must    be   used   to   avoid    a   tear  at   or 

'  See  article  by   Biihlig  on  general  and  special    methods  for    examining  the 
brain  and  spinal  cord;    "Cleveland  Medical  Jonr..  "  Jan.,  1904,  p.  28. 


POST  M « ) K T !•:  M    !•:  X  A  M  1  X  A  '1  I O N  S . 


around  the  ear,  as  tension  is  produced  by  ])ulling  the  anterior  and 
posterior  scalp-flaps  down;  to  avoid  this  unsightly  tear,  which  may  run 
down  in  front  of  the  ear.  insert  the  knife  under  the  skin,  in  the  incision 
already  made,  just  behind  the  ear,  and  dissect  the  skin  free  from  the  deeper 
structures  behind  and  in  front  of  the  ear.  The  scaljj-flaps,  as  already  de- 
scribed, do  not  include  the  temporal  fascia  or  muscle,  l)oth  of  which  are 
now  cut  through  and  reflected  in  the  line  of  the  contemplated  saw-cut. 
All  soft  tissues  should  be  incised  and  pushed  out  of  the  way  of  the  saw, 
otherwise  they  pack  the  teeth  of  the  instrument  and  greatly  impede  saw- 
ing. When  the  skull-cap  is  replaced,  the  fascia  and  the  muscles  may  be 
sewed  together,  thereby  securing  the  bone  in  place — a  matter  of  great 
importance  in  private  postmortems  when  the  body  is  to  be  exposed  at  a 
funeral  or  to  friends. 

Inspect  the  skull  for  evidence  of  injury  or  disease.  In  opening  the 
skull  there  are  three  methods  of  procedure— one  should  never  be  used 
when  it  can  be  avoided, 
one  may  be  used  in  a  few 
cases,  and  one  is  applica- 
ble in  the  vast  majority  of 
instances:  (i)  The  "un- 
dertaker's cut"  is  made  by 
sawing  across  the  forehead 
just  back  of  the  hair  line, 
from  one  temporal  fossa  to 
the  other,  and  carrying  a 
second  saw-cut  around  the 
posterior  base,  parallel  with 
the  base  line,  joining  the 
anterior  cut  in  each  temple. 
This  method  does  not  per- 
mit of  satisfactory  removal 
of  the  brain.  (2)  The 
second  method  should 
always  be  used  in  medico- 
legal cases,  and  whenever 
the  question  of  fracture 
mav    arise.      It    does    not 

dernand  the  use  of  a  chisel,  and  affords  abundant  opportunity  for  ex- 
amining the  interior  of  the  skull.  A  circumferential  line  is  drawn  around 
the  skull,  on  a  level  with  the  superciliary  ridge  in  front  and  the  occipital 
protuberance  posteriorly,  and  the  skull  sawed  through  at  this  line.  (3) 
The  third  method,  and 'the  one  most  commonly  employed,  consists  of  a 
V-shaped  incision;  as  viewed  laterally,  the  anterior  arm  of  the  V  is 
parallel  with  the  l)ase  of  the  skull,  on  a  level  with  the  su{)erciliary  ridge, 
and  extends  backward  i  cm.  behind  the  external  auditory  meatus. 
The  other  arm  of  the  saw-cut  passes  obliquely  across  the  vertex  just  back 
of  the  incision  already  made  in  the  scalp.  It  may  be  necessary  to  break 
out  the  angles  of  the  saw-cut  with  a  chisel;  care  must  be  used  not  to 
mutilate  the  ear  in  making  the  saw-cut.  The  adjustment  and  retention 
of  the  calvaria  in  place  mav  be  further  aided  by  making  the  posterior 
saw-cut  also  V-shaped.  The  angular  junction  of  the  two  lines  which 
form  the   V  is   directed   upward,  something   like   the  occipitoparietal 


It  is 


ig  -    Heavy  Link  I.ndk  atinc  Covrsf.  Tak:  '  t  in 

So-called  Undertaker's  Method. 
possible  that  the  base  line  as  drawn  in  this  illustration  is  too  low, 
however,  this  is  immaterial,  as  the  method  is  under  all  circum- 
stances to  be  avoided. 


TECHXIC. 


suture.  To  repeat:  This  makes  two  V-shaped  saw-cuts  as  follows: 
Viewed  laterally,  the  anterior  arm  of  the  first  V  is  parallel  with  the  base 
line,  and  extends  from  the  superciliary  ridge  to  just  behind  and  above 
the  external  auditoiy  meatus,  the  posterior  arm  of  this  V  being  sub- 
divided into  the  two  arms  of  a  second  V,  which,  as  viewed  from  behind, 
is  upside  down.  The  advantage  of  this  incision  lies  in  the  easily  adjusted 
calvaria,  the  wedge-shaped  cap  being  readily  replaced  and  secured  in 
position,  so  that  no  external  evidence  of  the  postmortem  will  be  visible 
when  the  scalp  is  returned  to  place  and  sutured. 

Inspect  the  interior  of  the  calvaria  for  evidence  of  injury  or  disease, 
noting  its  thickness  and  the  condition  of  the  diploe  and  of  the  external 
and  internal  tables.  The  dura  may  be  removed,  or,  rather,  reflected  back, 
by  incising  it  along  the  lower  saw-cut  and  detaching  the  falx  cerebri 
from  the  crista  galli.  When,  as  in  the  very  young,  the  dura  must  be 
removed  with  the  calvaria,  it  is  necessary  to  incise  that  membrane  along 

the  line  of  the  saw-cut, 
and  to  sever  the  falx  ante- 
riorly and  posteriorly  be- 
fore making  any  attempt 
to  raise  the  skull-cap. 

Inspect  the  surface  of 
the  brain  for  superficial 
injuries  or  disease,  but 
make  no  incision  into  it. 
It  may  here  be  necessary 
to  note  the  relation  of 
l)rain  landmarks  to  the 
skull,  fixed  points  of  the 
latter  being  selected  for 
the  comparison. 

The  brain  is  next  to 
be  removed,  beginning  in 
front  by  carefully  raising 
it  from  the  base,  being 
sure  to  raise  the  olfactory 
bulbs  with  the  hemi- 
spheres ;  still  cautiously 
elevating  the  hemispheres,  sever  the  nerves  as  they  pass  out  of  the 
skull,  those  in  front  first,  and  then  in  order  as  they  appear.  AVhen 
the  tentorium  is  reached,  detach  it  from  the  temporal  bone  and 
follow  the  base,  severing  the  nerves  as  they  find  exit  from  the  posterior 
fossa;  lastly,  pass  a  long,  slender-bladed  knife  along  the  basilar  pro- 
cess of  the  occipital  bone,  and  down  into  the  spinal  canal,  cutting  the 
cord  as  low  as  possible.  In  order  to  section  the  cord  as  nearly  trans- 
versely as  possible  and  to  avoid  the  oblique  incision  made  in  the  manner 
just  directed,  some  operators  prefer  the  use  of  a  myelotome.  After 
section  of  the  cord  the  entire  brain  can  be  easily  removed.  Complete 
the  examination  of  the  interior  of  the  skull,  noting  the  condition  of  the 
bone,  blood-vessels,  sinuses,  etc.,  dissecting  the  dura  from  the  base  to 
facilitate  the  examination  of  the  bone.  Before  detaching  the  dura  the 
contained  sinuses  should  be  opened  and  examined  for  evidences  of 
thrombi,  septic  processes,  etc.     The  posterior  part  of  the  orbit  and  the 


FrG.  20. — Circumferential  Saw-cut,  to  be  Preekrred  i.\  -Axl 

Medicolegal  Cases. 

The  exact  location  of  the  line  will  vary  slightly,  depending  upon  the 

conformation  of  the  skull.     It  is  usually  about  as  indicated  above. 


P ( I S T M () K T i:  M    EXAMINATIONS. 


eveball  may  l>c  oxaniintHl  by  ihiseling  the  root";  in  the  same  way  examine 
the  frontal,  sphenoid,  mastoid,  and  ethmoid  sinuses  and  the  internal 
ear.'  The  bniiii  should  be,  in  most  instances,  hardened  before  dissection ; 
if  this  can  not  be  done,  immediate  examination  may  be  made  as  follows: 
Make  a  careful  examination  of  the  meninges,  and  note  the  color,  con- 
sistency, etc.,  of  the  external  surfaces,  including  the  base;  the  con- 
sistency is  best  determined  by  gently  palpating  the  entire  cortex.  Ex- 
amine the  blood-vessels  at  the  base,  tracing  them  into  the  brain-tissue. 
An  incision  is  made  on  each  side,  just  over  the  corpus  callosum,  into  the 
lateral  ventricles,  and  continued  backward  and  forward,  that  they  may 
be  carefully  inspected;  the  amount  and  character  of  the  fluid  i)resent 
are  noted.  '  The  lateral  ventricles  are  joined  by  an  incision  through  the 
fornix,  reflecting  the  corpus  callosum  backward,  exposing  the  tissues 
beneath.  Search  for  hemorrhages,  areas  of  softening,  tinnor';  m- 
flammation,  abscesses,  etc. 
Lateral  incisions  are  now 
made  in  the  cortex  from 
the  ventricle  outward,  so 
as  to  note  the  condition- 
of  the  cerebral  substance: 
the  incisions  should  be 
parallel,  not  over  one  cen- 
timeter apart,  and  the 
membranes  should  not  be 
cut  through,  as  they  will 
retain  the  cut  parts  in 
position.  The  brain  is 
then  turned  over,  and  the 
tissue  of  the  base  exam- 
ined by  transverse  incis- 
ions through  the  medulla, 
cerebellum,  etc..  examin- 
ing for  such  changes  as 
previously  noted.  Weigh 
the  brain. 

While  occasionally 
much  information  can  be 
obtained  by  the  gross  ex- 
amination of  a  freshly  removed  brain,  improvements  in  histologu 
technic  have  made  the  microscopic  examination  of  greater  importance. 
In  order  to  obtain  valuable  information  from  this  method,  it  is  neces- 
sarv  to  secure  sections  which  permit  reconstruction  of  the  organ,  s<. 
that  the  connection  between  different  parts  may  be  traced.  This  ini- 
\)\\es  the  use  of  some  serial  method  similar  to  that  employed  in  em- 
bryologic  work.  The  size  of  the  human  brain  precludes  satisfactorv 
serial  sections  of  the  entire  mass,  and  as  the  serial  sections  are  for  the 
puqiose  of  demonstrating  histologic  lesions  in  paths  or  bundles,  each 
case  will  become  to  a  certain  extent  a  law  unto  itself.  In  the  interest 
of  complete  neurologic  investigation  the  pathologist  must  forego  the 
satisfaction  of  immediate  results  from  dissection  of  the  froh  ^^am. 

'  Schalle  (Virchows  Archiv,"  Bd.  Ixxi.  p.  206)  gives  details  -i 

r  txamininc'  the-  ort;ans  at  the  base  of  the  skull,  using  a  chain  >:nv 


KiG.  ;i.  -Wedge-shapkd  Calvaria  Removed  by  the  Link    u 
SAW-ruT  Recommended.     (See  Text.) 

Il  the  posterior  cut  is  so  mafle.  from  the  right  and  left  sides,  that  ihr 
point  just  above  the  figure  7  will  l>c  the  apc.x  of  a  triangle,  two 
sides  of  which  are  formed  by  posterolateral  saw-cuts,  there  will 
be  no  difficulty  in  retaining  the  wedge-shaped  calvaria  in  plan- 


24 


TECHNIC. 


It  is  desirable  to  harden  it  in  formaldehyde-water  (formalin  lo  parts, 
water  90  parts)  for  several  days  before  making  any  incisions  except 
those  through  the  margins  of  the  corpus  callosum  into  each  lateral 
ventricle,  which  are  preliminary  to  all  methods  of  dealing  with  the 
brain,  and  are  simply  to  promote  hardening  of  its  interior.  If,  how- 
ever, incisions  are  to  be  made  at  once,  the  pathologist  should  consider, 
in  relation  to  any  gross  lesion  present,  the  direction  of  tracts  which 


liHiiiilliihiilinlili 


Fig.  22. — Chisels. 
If  on]y  one  is  to  be  purchased,  the  lowest  one  will  be  of  most  use. 

mav  be  degenerated.  Such  tracts  should  be  cut  at  right  angles 
to  their  course  in  order  that  the  sections  may  be  used  for  micro- 
scopic study.  In  this  point  of  view  the  conventional  methods  of  Vir- 
chow  and  of  Pitres  are  objectionable.  The  safest  single  incision  is 
Dejerine's  horizontal  cut  passing  through  the  cerebrum  at  a  level  slightly 
beneath  the  upper  surface  of  the  callosum.  This  transects  the  basal 
ganglia  and  the  internal  capsule  at  their  widest  parts,  and  will  usually 
reveal  anv  gross  lesion.     If  this  is  not  conclusive,  another  section  may 


Fig.  23. — Myelotome. 
Used  for  separating  the  brain  from  the  spinal  cord.     The  advantage  claimed  for  this  instriiment  is  the  facility 
with  which  the  cord  may  be  cut  transversely,  thereby  avoiding  the  objectionable  oblique  incision  which 
is  usually  secured  when  the  ordinary  knife  is  used  for  the  same  purpose. 

be  made  i  cm.  lower  than  the  first  and  parallel  to  it.  A  section 
lengthwise  of  the  optic  tracts  will  show  their  connection  with  the  pri- 
mary optic  centers,  and  at  the  same  time  the  nuclei  and  fibers  of  the  third 
nerves. 

To  reserve  the  remainder  of  the  brain-stem  for  microscopic  study 
of  its  nuclei  and  nerve-roots,  the  most  advantageous  section  is  a  trans- 
verse one  in  the  upper  half  of  the  pons;  that  is,  above  the  fifth  nerves, 
which  are  about  half-wav  down  the   pons.     Above  all   to   be   avoided 


I'O  ST  M  t )  RT  1-;  M    !■:  X  A  M  I  X  A  III)  X  • 


arc  longituelinal  bisections  ol  the  bram-stcin.  For  the  study  ot  nerve- 
cell  bodies  and  of  neuroglia  small  portions  of  the  fresh  tissue,  removed 
from  the  paiticular  centers  of  the  cortex,  and  from  the  cervical  and 
lumbar  cord,  are  put  at  once  into  the  special  fixatives.  For  Marchi 
and  Weigert  pre|)arations  and  for  nuclear  and  general  staining,  the 
bulk  of  the  brain  and  cord  may  be  placed  in  Muller's  fluid,  or  in  Orth's 
mixture  for  twentv-four  to  forty-eight  hours,  followed  by  Muller's  fluid.' 

J  he  Pitrcs-Xo'tlnia^il  Mctlwd. — The  lateral  ventricles  are  opened  as 
described;  the  pons  and  cerebellum  are  severed  by  section  of  the  pe- 
duncles; the  cerebrum  is  divided  by  a  vertical  section  (longitudinal) 
through  the  median  line — the  third  ventricle;  each  half  of  the  cere- 
brum is  then  incised  from  above  downward,  transversely  to  its  long 
axis  and  as  nearly  as  may  be  parallel  with  the  fissure  of  Rolando:  (i) 
Five  centimeters  m  front  of  fissure  of  Rolando;  (2)  through  posterior 
margin  of  the  frontal  convolutions;  (3)  through  ascending  frontal  con- 
volution; (4)  through  ascending  parietal  convolution;  (5)  three  centi- 
meters posterior  to  hssure  of  Rolando;  (6)  one  centimeter  in  front  of 
parieto-occipital   sulcus. 

The  fixation  of  each  of  these  sections  completed,  serial  sections  are 
made  from  each  area.  While  much  more  tedious  and  requiring  greater 
care,  this  method  permits  of 
reconstruction  and  the  adapt- 
ation of  parts  so  as  to  follow 
fillets,  or  paths,  with  a  pre- 
cision not  possible  by  the 
cruder  methods. 

For  demonstrating  the 
condition  of  the  blood-vessels 
at  the  sacrifice  of  everything 
else,  the  brain  may  be  gently 
washed  away  and  the  blood- 
vessels floated  out  in  a  l)asin 
of  water. 

The  Spinal  Cord. — The  body  is  turned  upon  the  abdomen,  and 
blocks  are  so  arranged  as  to  arch  the  vertebral  column.  As  this  pro- 
cedure mav  cause  leakage  of  fluids  in  a  body  already  opened  ante- 
riorlv,  it  may  be  best,  in  private  postmortems,  to  examine  the  cord 
first;  after  the  body  is  turned  on  the  back,  little  if  any  fluid  should 
escape  through  a  properly  closed  posterior  incision.  An  incision  is 
then  made  through  the  skin,  over  the  spinous  processes,  extending 
from  the  occiput  to  the  sacrum,  and  the  muscles,  fascia?,  etc.,  detached 
from  the  vertebra-  so  as  to  expose  the  lamina*  on  both  sides.  These 
are  then  sawed  through,  the  saw  being  held  i)arallel  with  the  spinous 
processes  and  near  the  junction  of  the  lamina-  and  pedicles.  The  sec- 
tion extends  from  the  second  vertebra  to  the  sacrum.  The  excised 
strip  is  now  removed,  the  chisel  or  bone-cutting  forceps  being  used  as 
aids  if  necessary.-  Inspect  the  meninges  and  remove  these  with  the 
cord,  carefully  detaching,  with  a  sharp  knife,  th,-  Ti.TVP-rnots;  as  t!u-.- 

'   For  formulas  sec  chapter  on  Histologic  Technic 

^  Chavignv    ('La    Prcssc    Mddicale."  July  20.   1904,  p-  400/  atsi.nl. 

genious  lever  device  l"<^r  removing  the  spinous  processes  and  lammav      I  h. 

used  it.  but  LetuUe  writes  me  that  it  is  a  useful  appliance. 


Fic.  24. — Sc.\LPEL  WITH  Blade  Shaped  Sf)MK\vHAT  like  a 

BlSTOfRV. 

Useful  in  removing  ihc  brain  and  spinal  cord.     The  aneurysm 
needle  and  tenaculum  shown  arc  useful  at  limes 
not  essential. 


but  are 


26  TECHXIC. 

pass  out  of  the  canal.  The  lower  end  of  the  cord,  with  its  membranes, 
is  first  detached,  and  the  removal  continued  from  below  upward.  Dur- 
ing the  removal  of  the  cord,  whatever  traction  may  be  necessar}^  should 
be  made  on  the  niciiiiiges  only,  and  traction  on,  or  crushing  of,  the  cord 
should  be  carefuUv  avoided.  After  removal  of  the  cord  examine  bodies 
of  vertebrae;  dissect  out  and  preserve  a  number  of  the  intervertebral 
ganglia.  Open  the  dura  in  the  median  line  posteriorly  and  examine 
the  cord  by  making  transverse  incisions  one  to  two  centimeters  apart. 
The  examination  of  the  joints  and  bones  of  the  skeleton  may  have 
preceded  the  visceral  examination,  but  ordinarily  it  is  deferred  until 
that  has  been  completed.  Sometimes  it  is  desirable  to  obtain  bone- 
marrow  without  fracturing  or  otherwise  severing  the  continuity  of  the 
bone.  This  is  best  accomplished  by  two  saw-cuts  parallel,  four  or  five 
centimeters  apart,  and  extending  a  little  over  half-way  through  the 
bone;  by  means  of  a  chisel  this  block  of  bone  is  split  out,  bringing 
with  it  the  marrow.  A  block  of  wood  may  be  slipped  into  the  space 
occupied  by  the  piece  of  bone  removed,  and,  where  this  fits  tightly, 
bringing  the  tissues  together  over  it  will  usually  prevent  the  occurrence 
of  a  fracture  during  the  ordinary  handling  of  the  body. 


Fig.  25. — Double  Saw  (Rachiotome)  for  S.^.wing  through  the  Lamin.e  of  Both  Sides  at  Once. 
It  saves  time  and  labor,  but  equally  good  work  can  be  done  \rithout  it. 

The  removal  of  the  salivary  glands  is  not  often  demanded.  The 
sublingual  and  submaxillary  glands  may  ordinarily  be  removed  by 
the  method  already  described  when  considering  the  larynx  and  pharynx. 
A  portion  of  the  parotid  gland  can  sometimes  be  removed  by  dissect- 
ing the  skin  down  from  the  temporal  region  anteriorly,  and  below  the 
incision  already  advised  for  exposing  the  skull. 

By  LcHille's  method^  the  neck  and  the  thoracic  and  abdominal 
cavities  are  eviscerated  en  masse  and  the  subsequent  examination  of 
the  organs  begun  and  to  a  large  degree  completed  while  they  are  still 
attached  together.  To  accomphsh  this,  the  preliminary  incisions,  in- 
cluding opening  the  abdominal  cavity,  are  those  for  which  directions 
have  alreadybeen  given  (pp.  7  tog).  A  long  knife  is  passed  upward  through 
the  floor  of  the  mouth,  separating  the  tissues  from  the  inner  surface 
of  the  inferior  maxilla;    the  uvula  and  palatine  arches  are  freed  from 

1  I  have  taken  some  minor  liberties  with  Letulle's  plan,  which  to  one  having 
a  thorough  knowledge  of  anatomy  and  some  experience  in  postmortem  work.  I 
think  can  be  stronglv  recommended. 


.loKTKM    KXAMlNATItiN: 


their  osseous  altaclimcnts.     The  posterif)r  wall  ol"  the  j»har>ii.N   ■.>  -U- 
tached    from    the    subjacent    bone   and    ])ullcd    downward.     The   large 
arterial  trunks  in  the  nock  and  the  subclavian  vessels  are  divided;    the 
entire  mass  is  now  ]nilled  downward,  the  section  bcin^  ma<le  close  to 
the   vertebra^  until   the   diaphraj^mi   is   reached.     This  structure   is  in- 
cised along  the  ril)S  and  vertebra",  and  by  keei)ing  close  to  the  poste- 
rior abdominal  wall,  the  evisceration  is  completed.     When  the  floor  of 
the  pelvis  is  reached,  the  incision  in  the  male  differs  from  that  used 
in  the  female.     In  the  former  the  bladder  is  dissected  from  the  anterior 
abdominal  wall  and  pubis,  after  which  a  long  knife  is  thrust  downwar<l 
under  the  pubic  bone,  and,  with  the  scrotum  pulled  upward,  is  made 
to  emerge   at  the   perineoscrotal   margin   near  the   median   line,   from 
which  i)oint  it  is  carried  around  the  sides  of  the  pelvic  outlet  in  such  a 
manner  as  to  remove  anus  and  pelvic  floor;   where  permissible,  the  y)enis 
and   testes  may  be  retracted 
and  removed  \vith  the  mass. 
In  America,  at  least,  this  ex- 
cision of  the  external  genitalia 
will  rarely  be  permitted,  and 
hence   the  incision   had    best 
pass  through  the  bull)Qus  ])or- 
tion  of   the  urethra,  allowing 
that  structure  to  be  removed 
with  the  bladder,  rectum,  and 
other  viscera.     In  the  female 
the  knife,  thrust  down  from 
above,  emerges  at  the  side  of 
the     vulva     and     is     carried 
around  the   anus,  similar  in- 
cisions being  made  on  either 
side;    the    two    incisions    are 
ioined  above    the  vidva  and 
the  dissection  from  the  pubic 
bone  completed.    The  umbili- 
cal    attachments    should    be 
severed  before  evisceration  is 
begun;     in    the    infant    it    is 

well  to  cut  around  and  excise  the  umbilicus  and  its  vessels; 
necessarv  in  the  adult.  i     i  t 

The  anterior  relations  of  the  organs  may  have  been  descnbetl  be- 
fore evisceration;  usuallv  this  course  is  to  be  recommended.  After 
removal  the  mass  is  laid  upon  its  anterior  surface  and  the  examina- 
tion continued  in  the  following  order:  (i)  Large  and  small  azygos 
veins.  (2)  The  thoracic  duct,  including  the  receptaculum ;  the  former 
is  detached  throughout  its  extent  from  the  receptaculum  to  its  junc- 
tion with  the  vein,  (.s)  Examine  and  remove  the  adrenals.  (4I  Iso- 
late the  ureters.  (5)  Disengage  the  kidneys,  exposing  the  arteries  and 
veins  which,  after 'examination,  should  be  sectioned,  using  care  not 
to  wound  the  pelvis  or  ureter.     The  kidneys  are  then  laid  down  on 

either  side,  the  ureteral  connections  with  the  bladder  being  maiT'*  

(6)  Open  the  al)dominal  and  thoracic  aorta  from  the  iliac  ve- 

ward      (;)  Open  the  vena  cava.     (8)   Raise  and  pull  to  one  "^i  !c  tne 


KlG.  26. 


-Pkrin-ealIm  1  .   ■-—■■  \ 

ETC.,   IN    THE    Si\Lt..—iLtluiU.) 


this  is  not 


2  8 


TECHNIC. 


abdominal  aorta  and  cava,  exposing  the  trunk  of  the  portal  vein  and 
its  larger  branches,  and  open  them.  (9)  Expose  the  common  duct, 
dissecting  upward  to  the  cvstic  and  hepatic  ducts,  which  should  also 
be  brought  into  view.  (10')  Expose  the  posterior  surface  of  the  pan- 
creas, which  may  now  be  exammed;  the  organ,  however,  should  not 
be  detached  from  the  duodenum  until  examination  of  the  intestine 
has  been  completed.  (11)  The  aorta  is  cut  transversely  at  the  level 
of  the  renal  arteries  and  dissected  upward  to  the  arch.  (12)  Raise 
the  esophagus  near  its  middle,  dissecting  downward  to  the  cardia  and 
upward  to  the  pharvnx.  (13)  Examine  the  organs  from  the  mouth 
and  pharvnx,  including  the  palate,  tonsils,  tongue,  and  sublingual 
glands.  (14)  Separate  the  upper  attachments  of  the  esophagus,  which 
mav  be  ligated  at  its  upper  or  lower  end,  whichever  in  a  given  case 
seems  desirable.  (15)  Examine  the  epiglottis  and  open  the  larynx;  at 
this  time  the  larvngeal  nerves  may  be  dissected.  (16)  Examine  and 
open  the  trachea'  and  primitive  bronchi  by  continuing  downward  the 
incision  alreadv  made  in  the  larynx.  (17)  Expose  and  examine  the 
pulmonarv   pedicle,   not   incising  the   vessels,   which   are  opened  later. 

(18)  Freethecervico-thoracic 
portion  of  the  pneumogastric 
nerve.  (19)  The  lymph-nodes 
of  the  posterior  part  of  the 
body.  This  completes  the 
posterior  examination.  The 
mass  is  now  turned  over,  be- 
ing careful  to  retain  the  nor- 
mal relations. 

The  examination  of  the 
organs  from  the  anterior  sur- 
face is  conducted  in  the  fol- 
lowing order:  (i)  Examine 
and  remove  the  thymus.  (2) 
Isolate  and  remove  the 
thyroid  gland,  noting  its  re- 
lation to  the  trachea  and 
the  presence  or  absence  of 
a  pyramidal  lobe.  The  pos- 
sibilities of  aberrant  masses  of  thyroid  tissue  should  be  borne  in  mind 
during  the  subsequent  examination  of  the  mediastinal  structures.  (3) 
Open  the  superior  vena  cava  and  its  branches.  (4)  Examine  the  freshly 
opened  veins  for  the  mouth  of  the  thoracic  duct.  (5)  Open  and  in- 
spect the  pericardium.  (6)  Examine  the  cardiac  plexus  of  nerves.  (7) 
Examine  the  arch  of  the  aorta,  noting  its  relation  to  the  pulmonary 
trunk  and  branches.  Cut  through  the  aorta  at  the  cardiac  end  of  the 
incision  already  made  m  the  arch.  (8)  Expose  and  open  the  pulmo- 
nary trunk  and  branches  to  the  entrance  of  the  latter  into  the  lung.  (9) 
Expose  and  open  the  extrapulmonary  part  of  the  pulmonary  veins. 
(10)  Complete  the  examination  of  the  pulmonary  pedicle,  examining 
the  peribronchial  glands,  at  which  time  the  lungs  may  be  separated, 
although  usually  this  is  done  after  the  heart  is  removed.  (11)  Ex- 
ternal examination  of  the  heart.  (12)  Cut  the  pulmonary  arteries  and 
aortic   arch   and   finallv   the  veins   entering  the   auricles;    remove   the 


Fig.  27. — Perineal  Incision  for  Removing  the  Rectum, 
Anus,  and  Reproductive  Organs  of  the  Female. 
—{Letulk.) 


I'OSTMdkTKM    KXA.MIXATUjNS.  21) 

heart.  (13)  Section  the  pulmonary  pedicles  and  remove  the  lun^s. 
(14)  Complete  examination  of  the  diaphragm.  (15)  Examine  the 
liver,  gall-bladder,  and  cystic  duct;  excise  the  liver.  (16)  Remove 
the  spleen.  (17)  Isolate  and  examine  externally  the  stomach,  duo- 
denum, and  pancreas,  ligating  the  jejunum  at  its  origin  and  bringing 
with  the  mass  the  already  isolated  esophagus.  (18)  Examine  and  re- 
move the  ileum  and  large  intestine  from  above  downward,  essentially 
as  already  directed  on  page  19.  (19)  Complete  the  removal  of  the 
mass  containing  the  esophagus,  stomach,  pancreas,  and  duodenum; 
open  esophagus,  stomach,  and  duodenum;  examine  relations  of  latter 
to  pancreas;  examine  pancreatic  ducts  and  complete  examination  of 
pancreas.  (20)  Complete  the  examination  of  the  peritoneum,  including 
the  mesentery,  etc.  (21)  Complete  the  examination  of  the  urinary 
organs,  including  the  kidneys,  ureters,  bladder,  and  urethra.  (22)  Exam- 
ine (A)  Prostate,  seminal'  vesicles,  testicles,  and  ducts,  or  (B)  tubes, 
broad  ligaments,  ovaries,  vulva,  vagina,  and  uterus. 

In  order  to  make  a  bacteriologic  examination,'  it  will  be  necessary 
to  have  on  hand  a  Bunsen  burner,  alcohol  lamp,  or  other  means  of  steriliz- 
ing the  instruments  used.     Cover-glasses,  cover-glass  forceps,  platinum 


1  ic  28. — Bone-Cutting  1'orieps. 
These  are  not  absolutely    essential,  but    will  be    convenient.     They    should    be    long— not    less    than    tiflccn 

centimeters. 

wire,  various  culture  media,  and  labels  will  be  needed.  In  order  to 
secure  material  not  contaminated  by  accident,  it  will  be  necessary  to 
enter  all  cavities  through  an  aseptic  'field.  The  disinfection  of  the  area 
is  best  accomplished  by  heat.  In  order  to  secure  inoculations  from  the 
peritoneum,  it  will  be  necessary,  as  soon  as  the  wound  in  the  abdominal 
wall  approaches  the  cavitv,  to  sear  the  surface  with  a  hot  scalpel,  or, 
what  is  better,  a  spatula';  the  searing  must  be  thorough;  through 
the  seared  surface,  with  instruments  kept  sterile  by  frequent  passage 
through  the  flame,  the  wound  is  cautiously  extended  until  the  cavity  is 
reached.  At  once  inoculations  and  cover-glass  spreads  are  made.  In 
a  like  manner  the  pleura  may  be  opened  through  an  intercostal  space. 
Inoculations  from  the  interior  of  the  pericardium  are  best  obtained  by 
cautiouslv  searing  the  fold  raised  as  already  directed  (p.  10),  and  punctur- 
ing with  a  hot  knife  or  scissors.  To  secure  blood  from  the  heart,  a  part 
of  the  surface  is  sterilized  bv  searing  with  a  hot  iron,  or  one  of  the  great 
vessels  mav  be  similarlv  treated  and  opened,  using  for  this  purpose  a 
hot  knife  or  scissors.  A  platinum  loop  may  then  be  thrust  into  the 
cavitv,  and  inoculations  and  spreads  made  in  the  u.sual  manner.    As  soon 

'  As  to  the  value  of  bacteriologic  examinations  postmortem,  see  Chvostck 
and  Egger  ("Wien.  klin.  Woch..'  1897.  x-  3).  Achatrd  and  Phulmn  (  Arch,  de 
M6d.  Exp.."  vii.  I,  p.  25).  Simmonds  (' Virchow's  Archiv,  1904.  Bd.  175.  M.  5). 
rrradwohl  ("Annalcs  de'l'Inst.  Pasteur."  Dec.  25.  1004.  P-  /'i?'*- 


30 


TECHNIC. 


as  the  skull  cap  is  removed  the  dura  should  be  seared,  jjunctured  with 
a  sterile  knife  or  scissors,  and  cultures  and  spreads  obtained  from 
beneath. 

Systematizing  the  Description. — In  considering  organs  a  definite  field 
or  plan  should  be  adopted.  Of  course,  this  will  be  quite  often  varied,  but 
it  has  the  advantage  of  occupying  no  more  time  than  any  other  method, 
and  assures  a  svstematic  record  which  makes  all  postmortems  comparable. 
The  following  "is  advised,  although  each  worker  will  probably  acquire  a 
routine  of  his  own:  {i)Malpositioii,  and,  if  out  of  place,  is  the  malposition 
congenital  or  acquired,  and  what  influence  has  it  had  on  the  position  or 
function  of  other  organs:  c.  g.,  a  misplaced  right  kidney  may  press  upon 
the  duodenum  or  bile-duct  or  upon  both.  After  removal  it  is  too  late 
to  determine  such  facts,  which  may  be  of  the  highest  importance  in 
explaining  symptoms.  (2)  Malformations.  (3)  Make  measurements  of 
the  organ  and  '■d.'eigh  it;  as  the  organ  can  be  weighed  only  after  removal, 
and  as  the  removal  severs  its  connection  with  the  body,  note  must  be 
made  of  color,  consistency,  density,  and  shape,— the  latter  being  outlined 
when  the  measurements  are  made, — and  a  full  description  of  its  external 
appearance  must  be  given ;  at  the  time  of  severing  its  attachments  the  full- 
ness of  the  blood-vessels,  the  presence  or  absence  of  edema,  and,  if  it  pos- 
sesses a  duct,  the  condition  and  contents  of  that  structure,  must  all  be 
recorded.  Whatever  observations  are  to  be  made  with  regard  to  the  ducts 
of  organs  must  be  completed  before  severing  their  connections.     These 

studies  enable  one,  to    a  certain    extent,  to 
record  the  presence  or  absence  of  the  follow- 
ing points,  which  come  next  in  order:     (4) 
Atrophy,  including  hypoplasia  or  aplasia.    (5) 
Hypertrophy,  including  hyperplasia.     (6)    /;/- 
Fig.  29.— Postmortem  Needles.        filtration       (7)    Degeneration.      (8)    Infiamma- 
'^'"^ete?rYon1f^'d^or4i^nd^^"t      tioHS ,  mcludmg  ^cute  tnfcctions .     (9)  Lcsions 
heavy.  qj  systcms:    (a)   vascular;    (b)'  lymphatic;    (c) 

nervous.  (lo)  Chronic  infections.  (ii)  Tu- 
mors. (12)  Parasites.  If  the  steps  indicated  be  followed,  l)ut  httle  will 
be  overlooked. 

As  soon  as  an  organ  is  incised  pieces  should  be  removed  and  fixed 
for  microscopic  study;  the  records  may  be  completed  after  the  micro- 
scopic examination  is  finished. 

Restoration  of  the  Body. — The  cavities  opened  are  wiped  dry.  Open- 
ings in  the  neck  likely  to  drain  into  the  mouth,  and  defects  in  the  pelvic 
floor,  had  best  be  closed  preferably  by  suture  and  by  packing  with  gauze 
or,  what  is  still  better,  gauze  pads  containing  bran.  Such  pads  may  also 
be  used  for  re-establishing  the  contour  of  the  body,  preventing  collapse 
of  the  sternum,  and,  if  the  larynx  and  trachea  have  been  removed,  may 
be  used  for  restoring  the  rotundity  of  the  neck.  The  breast-plate  is 
replaced  and  loosely  attached  in'  position  by  lateral  sutures.  The 
incision  in  the  anterior  median  line  is  now  closed.  If  just  before  the 
last  stitches  are  tightened  300  or  400  c.c.  of  formahn  is  poured  into 
the  body  cavity,  its  absorption  by  the  bran  will  greatly  retard  decom- 
position. 

The  Head.— The  brain  should  rarely  be  returned  to  the  skull  cavity, 
as  it  rapidly  softens  and  forms  a  semifl'uid  material  that  tends  to  escape 
in  spite  of  the  usual  precautions.     The  cranial  cavity  may  be  loosel}' 


POSTMORTKM    EXAMINATIONS.  jt 

packed  With  paper,  cotton,  or  bran  i)ads,  or  oakum,  which  1  believe  is  the 
best.  Many  ingenious  methods  have  been  devised  for  retaining  the 
calvaria  in  position.  If  the  temporal  angles  are  broken  out  with  a  chisel, 
usually  there  is  enough  beveling  to  prevent  lateral  displacement.  This 
is  j^articularly  true  if  the  temporal  fascia  and  muscle  above  and  below 
the  line  of  incision  are  sutured  tightly.  Where  a  circumferential  cut  has 
been  made,  it  is  best  to  fasten  the  skull  cap  in  position  by  wire  sutures 
introduced  through  drill-holes  in  the  temporal  and  occipital  regions. 
Where  the  ordinary  V-cut  recommended  on  page  21  is  emjiloyed,  Sice's 
ingenious  method  will  be  found  useful.  The  anterior  saw-cut  is  extended 
I  or  2  cm.  backward  in  each  temporal  region;  the  posterior  cut  is  pro- 
jected forward  in  a  like  manner.  Through  these  two  slits  narrow  roller 
bandages  are  passed,  the  calvaria  replaced,  and  the  bandages  carried 
upward,  drawn  tightly  over  the  convexity,  and  pinned  in  two  places. 
The  skin  flaps  are  then  replaced  and  sutured.  The  spinal  canal  is  wiped 
dry,  loosely  packed  with  cotton,  sawdust,  bran,  or  candle-wicking,  the 
bone  replaced,  and  the  skin  sutured  in  position. 

Preservation  of  Tissues. — The  sulistance  commonly  used  for  the  pre- 
servation of  specimens  lias  been  alcohol;  with  this  reagent  color  is 
lost,  density  altered,  and  contour  indifferently  retained.  Of  late 
formalin'  has  been  adopted  as  a  routine  preserving  agent,  the  strength 
commonly  used  being  ten  parts  of  the  commercial  article  and  ninety 
parts  of  water.  Specimens  preserved  in  formalin  may  l)e  carried  into 
Miiller's  fluid  for  examination  of  the  nervous  tissues  and  may  also  be 
treated  by  ^Marchi's  method  for  the  demonstration  of  fat.  They  are 
better  adapted  to  histologic  examination  than  specimens  preserved  in 
alcohol,  but  for  cytologic  study  compare  unfavorably  with  specimens 
fixed  by  approved  agents  to  be  mentioned  under  Histologic  Technic. 
For  the  brain,  spinal  cord,  and  peripheral  nerves  Orth's  fluid  is  gener- 
ally used.     Muller's  fluid  is  prepared  as  follows: 

Potassium  bichromate j.5   gm. 

Sodium  sulphate.  i.o  gm. 

Water 1  00.0  c.c. 

Orth's  fluid  is  prepared  by  adding — just  before  using — 10  c.c.  of  formalin 
to  100  c.c.  of  ^fuller's  fluid.  The  solution  must  be  changed  at  the  end 
of  twenty-four  to  forty-eight  hours,  and  by  the  third  of  fourth  day  had 
best  be  replaced  by  Muller's  fluid.  Large  masses,  such  as  the  brain, 
require  a  longer  time  and  should  be  freely  incised  when  the  solution  is 
first  changed.  Orth's  fluid,  like  that  recommended  by  M idler,  darkens 
the  tissue,  alters  its  macroscopic  appearance,  and  is  ill-adapted  to 
material  intended  for  gross  demonstration  or  museum  exhibition. 

Organs  or  specimens  not  too  large  (one  kilo)  can  be  preserved  in 
formalin  vapor  by  placing  them  on  a  bed  of  cotton  in  an  air-tight  jar. 
previously  moistening  the  cotton  with  pure  formalin,  and.  for  the  first 
few  days,  keeping  the  specimen  covered  by  filter-paper  moistened  with 
formalin. 

For  the  preservation  of  color  no  method  yields  results  comparable 

*  Formalin    is   a  proprietan,'  article — a   forty  per  ition  <->f 

formaldehyde  gas.  The  original  formalin  was  cxpen.sivc,  bu' 
solutions,  under  other  names — as  formalosc.  formol — can  be  > 
price  making  preservation  by  this  method  cheaper  than  with  ni.     ti 


32  TECHXIC. 

to  those  obtained  by  that  devised  by  Kaiseriing,  of  which  many  modi- 
fications  have   been  suggested.^     Two  solutions  are   necessary; 

Si>lu:ion  A .  Solution  B. 

Formalin 250  c.c.  Acetate  of  potassium.      200  gm. 

Nitrate  of  potassium, .  10  gm.  Glycerin 400  c.c. 

Acetate  of  potassium.  30  !^m.  Water 2000  c.c. 

Water    i  liter.  Thymol  to  saturation. 

The  specimen  to  be  preserved  is  quickly  and  lightly  washed  in 
water  to  remove  adhering  blood  only;  it  is  then  placed  for  from  one 
to  twenty-four  hours  in  solution  A,  at  the  end  of  which  time  it  is  changed 
to  fresh  solution  A,  where  it  is  allowed  to  remain  for  from  two  to  thirty- 
six  hours.  Wash  in  running  water  for  from  fifteen  minutes  to  one 
hour  and  transfer  to  eighty  per  cent,  alcohol;  as  soon  as  the  color 
begins  to  reappear  the  specimen  is  transferred  to  ninety-five  per  cent, 
alcohol,  in  which  it  should  be  allowed  to  remain  until  the  color  is  fully 
restored.  This  process  of  development  in  the  alcohol  must  be  watched 
closely,  for  if  allowed  to  go  too  far  the  color  will  be  irretrievably  lost; 
as  soon  as  the  color  is  restored  transfer  the  specimen  to  solution  B, 
which,  at  the  end  of  twenty-four  to  forty-eight  hours,  had  best  be 
changed,  as  any  residual  alcohol  tends  to  bleach  the  colors.  In  order 
to  prevent  the  growth  of  molds  solution  B  must  be  kept  saturated 
with  thymol,  a  small  lump  of  which  should  be  left  constantly  in  all 
vessels  containing  the  fluid.  The  same  result  can  be  accomplished  by 
adding  formalin,  0.75  to  i  per  cent. 

Specimens  prepared  by  the  Kaiseriing  method  may  be  preserved 
without  fluid  in  air-tight  jars  containing  a  luinp  of  th3miol.  Little - 
John  recommends  this  method  for  the  preservation  of  stomachs  from 
cases  of  corrosive  sublimate,  carbolic  acid,  and  creosote  poisoning, 
which  may  be  kept  indefinitely  in  air-tight  jars,  bacterial  growth  be- 
ing prevented  by  the  poison  contained  in  the  specimen. 

Small  cysts,  such  as  those  of  the  echinococcus,  are  best  preserved 
in  a  ten  per  cent,  aqueous  solution  of  chloral. 

^  See  papers  by  Coplin  and  also  Herring  ("Jour.  Amer.  Med.  Assoc,"  August 
13,  1904);  Watters  ("N.  Y.  Med.  Jour.,"  August  23,  1902);  paper  by  M.  E.  Ab- 
bott ("Amer.  Med./'  April  4,  1903)  on  the  "Classification  of  Museum  Speciinens  " ; 
also  the  writer's  papcjs  in  the  "Proceed,  of  the  Path.  Soc.  of  Philadelphia,"  1903- 
1904  and  1904-1905.  For  the  "Dangers  of  Formol "  see  Spitzka  ("Science,"  July 
17,   1903,  p.  87). 


CHAPTER  11. 

HISTOLOGIC  METHODS.' 

Fixation. — Sections  of  the  fresh  tissue  may  be  cut  either  free-hand 
or  by  means  of  Valentine's  knife,  which  consists  of  two  parallel  blades 
of  the  utmost  sharpness,  separated  from  each  other  by  a  small  aper- 
ture just  as  wide  as  the  section  is  to  be  thick.  Both  methods  are 
unsatisfactory,  and  are  rarely  used.  Fresh  tissue  may  be  cut  by  freez- 
ing, as  will  be  directed  later,  but  for  a  satisfactory  study  of  cell  chem- 
istry and  morphology,  and  tissue  architecture,  it  is  especially  important 
to  subject  the  material  to  the  action  of  some  agent  which  will  destroy 
all  vitality,  arrest  metabolic  and  lytic  processes,  and  prevent,  as  nearly 
as  possible,  all  those  postmortem  changes  which  lead  to  chemic  and 
structural  alteration.  This  process  is  called  fixation  and  the  agents 
used  fixatives.     The  following  are  especially  commended: 

(a)  Chromo-aceto-osmic  acid  mixture  (Flemming's  solution).  For 
this  solution  keep  on  hand  the  following  stock  solutions,  and  make  up 
for  use  as  wanted,  in  the  proportion  given: 

(^)uijnli,'y  neeiltd  lo  makf 
Slock  solutions  to  be  kept  on  hand.  up  FUniming's  solution. 

I  per  cent,  aqueous  solution  of  chromic  acid 25  volumes. 

I         ••  ■'  ■•  ■■  osmic  ■■      10 

I        ••                                            ■■  acetic  .10 

Water,  .  .  .55 

All  the  water  used  in  making  the  stock  solutions  or  the  final  mix- 
ture must  be  distilled,  and  all  containers  should  be  chemically  clean 
and  dust-free. 

Fixation  of  small  pieces  will  be  complete  in  from  one-half  to  two 
hours,  although  a  longer  time  may  do  no  injury.  A  period  beyond 
a  few  hours,  however,  is  likely  to  make  the  tissues  brittle.  After  fixa- 
tion, wash  thoroughly  in  water.  This  is  best  accomplished  by  wash- 
ing in  flowing  water  for  at  least  six  hours.  Proceed  to  embed  at  once 
or  preserve  in  seventy  per  cent,   alcohol  until  needed. 

(6)  Platino-aceto-osmic  mixture  (Hermann).  Like  the  foregoing, 
it  is  best  freshly  prepared: 

Quantity  nftdrd  lo  makr 
Slock  solutions  lo  be  U  kept  on  hand.  up  abm^  solution. 

1  per  cent,  aqueous  solution  of  platinic  chlorid 15  volumes. 

2  ■'  "  "  "1  >sniic  aciil 2 

Glacial  acetic  acid .1  velum. 

'  In  the  present  edition  of  thi>  hhok  in.  ii    na\<    nvi  n  him  rtcd,  whi 

importance  seemed  to  demand  it.  such  technical  direction.s  as  may  1 
for  the  demtmst ration  of  special  reactions  or  methods.      When  seau! 
rections  bearing  on  some  point,  the  student  is  advised  t<>  consult  the 
attempt  can  he  made  in  such  a  work  as  this  to  go  into  the  sul>i>  .  ♦ 
technic  with  elaborate  detail.     A  few  methods  can  be  taught,  it  ; 
oughly;    but  for  further  detail  as  to  special  methods  the  student  li 
ize  himself  with  that  best  of  all  books  for  the  worker  with  the  r 
Microtomists  Vade-mecum."  by  Arthur  Belles  Lee.     See  also  ret' 
4  33 


34 


TECHNIC. 


This  solution  is  used  as  already  directed  for  Flemming's  solution, 
and  should  be  followed  by  the  same  careful  washing.  Tissue  so  pre- 
pared may  be  treated  as  already  directed  for  tissue  prepared  in  Flem- 
ming's solution. 

(c)  The  most  useful  fixing  agent  for  general  use  is  corrosive  sub- 
limate. In  solution  it  keeps  w^ell  and  fixes  thoroughly,  although  for 
pure  cell  study  the  foregoing  solutions  are  probably  better.  Heiden- 
hain's  solution  is  prepared  by  dissolving  125  gm.  of  corrosive  subli- 
mate in  a  liter  of  0.5  per  cent,  solution  of  sodium  chlorid  in  water. 
The  solution  of  the  corrosive  sublimate  being  effected  in  the  boiling 
salt  solution,  on  cooling  its  crystals  are  thrown  down,  but  are  again 
taken  up  as  the  solution  is  used  over.  Small  pieces  of  tissue  fix  in 
this  solution  in  from  one-half  to  two  hours.  The  used  solution  is  fil- 
tered back  into  the  stock  solution,  and  the  tissue  washed  in  water  or, 
what  is  better,  seventy  per  cent,  alcohol.  A  little  experience  soon 
enables  one  to  infer  when  the  stock  solution  has  become  exhausted. 
The  fixing  solutions  of  Zenker,  Petrunkevitch.  and  Bensley  are  also 
excellent  for  routine  work. 

Petrunkevitch' s  Solution.  Bcnsley's  Solution. 

Alcohol,  absolute 200  c.c  Potassium  bichromate,    i    % 

Water 300  c.c.  aqueous  solution, 50  c.c. 

Glacial  acetic  acid,.  .  .  .      90  c.c.  Corrosive  sublimate,  saturated 

Nitric  acid,  pure  cone.      10  c.c.  alcoholic  solution, 50  c.c. 

Corrosive  sublimate,  .  .      55  gm.  Glacial  acetic  acid, 5  c.c. 

The  solutions  must  be  kept  separately  and  mixed  when  needed. 

The  tissues  are  transferred  from  this  solution  to  seventy  per  cent, 
alcohol  containing  a  trace  of  iodin;  this  should  be  changed  frequently 
and  the  specimens  kept  in  seventy  per  cent,  alcohol  until  needed. 
Zenker's,  Bensley's,  and  Orth's  fluids  require  from  twelve  to  twenty- 
four  hours  for  fixation;  the  tissues  should  then  be  washed  in  running 
water  and  finally  carried  through  iodized  alcohol.  Tissues  fixed  in 
mercurial  solutions  contain  crystals  which  must  be  removed,  as  they 
obscure  the  microscopic  picture,  and,  I  am  inclined  to  beHeve,  cor- 
rosive sublimate  left  in  a  specimen  renders  it  more  dense,  and  with 
hard  structures  such  as  fibrous  tissue  and  masses  of  unstriped  muscle 
(uterus),  the  intense  hardening  may  prevent  satisfactory  sectioning. 
The  corrosive  sublimate  may  be  removed  after  sectioning  (p.  41)  or 
during  the  process  of  dehydration;  if  the  seventy,  eighty,  and  ninety 
per  cent,  alcohols  are  faintly  tinged  (light  canary  yellow)  by  the  addi- 
tion of  iodin,  the  sections  will  contain  no  mercurial  precipitate;  the 
iodin  must  be  thoroughly  removed  in  subsequent  alcohols,  otherwise 
the  tissues  will  be  brittle. 

In  fixing  by  any  of  the  above  methods,  the  tissue  should  be  in 
small  pieces,  not  larger  than  0.5  to  i  cm.  cube.  The  quantity  of  the 
fluid  used  should  be  abundant,  and  exceed  several  times  the  volume 
of  the  tissue  to  be  fixed. 

For  the  preparation  of  tissue  containing  nerves,  or  the  central 
nervous  system,  nothing  has  been  more  generally  used  than  bichro- 
mate of  potassium.  It  is  used  in  two  to  five  per  cent,  aqueous  solu- 
tions, or  as  Muller's  or  Orth's  fluids  (p.  31);    it  also  enters  into  Zen- 


HISTOLOGIC   MKTIIODS. 


35 


ker's  and  Erlicki's  solution,  the  former  much,  and  the  latter  but  little 
used. 

/.cnkrr's  Solution.  Eriirkis  Solution. 

Corn^sivc   sublimate.  2.5  gm.  Potassium  Ijichro- 

Mullcr's  tiuiil loo.o  cc                         mate 2    jjm. 

Just  before  using  add  Clipper  sulphate. ...  1.08  gm. 

Glacial  acetic  acid  5.0  c.c.  Water  100. o    cc. 

Orth's  and  Erlicki's  fluids  fix  and  harden  much  more  rapidly  than 
Midler's  fluid  alone;  in  either  of  these  solutions  a  spinal  cord  would 
require  but  two  or  three  weeks,  or  even  less,  while  with  Miiller's  fluid 
a  much  longer  time  is  necessary. 

Alcohol  is  sometimes  used  as  a  fixative.  To  be  efficient  it  must  be 
as  nearlv  absolute  as  possible.  Weaker  solutions  give  rise  to  easily 
recognized  and  quite  characteristic  artifacts.  When  rapid  fixation  and 
coincident  dehydration  are  desirable,  a  saturated  alcoholic  solution  of 
corrosive  sublimate  may  be  used.  For  the  demonstration  of  bacteria 
in  tissue,  fixation  by  alcohol  is  permissible;  it  has,  however,  no  ad- 
vantages over  corrosive  sublimate,  even  for  this  purpose,  and  is  always 
associated  with  a  verv  grave  disadvantage,  in  that  one  desiring  to  study 
the  nuclei  mav  find  that  the  fixative  has  not  properly  preserved  them. 

Alcohol  is  largely  used  as  a  dehydrating  agent  and  for  the  preserva- 
tion of  tissues  during  the  interval  "between  fixation  and  the  final  steps 
in  the  embedding  process.  It  is  the  ideal  agent  for  neither  purpose,  but 
for  the  present  it  seems  to  be  the  best  that  we  possess. 


SECTION  CUTTING. 

Infiltration  Methods. 

I.  Paraflan. — After  fixing  and  washing  as  already  directed,  t'ne  tissue 
to  be  infiltrated  is  dehydrated  by  passing  through  alcohols  of  increasing 
strength  —  seventy  per  cent., 
twenty-four  hours;  eighty  per 
cent.,  twenty-four  hours;  ninety 
per  cent.,  twenty-four  hours; 
absolute,  twenty-four  hours.  As 
alcohol  does  not  mix  with  par- 
aflin.  it  must  be  displaced  by  some 
paraffin  solvent.  For  this  purpose 
numerous  reagents  have  been  used, 
such  as  chloroform,  turpentine, 
xylol,  toluol,  benzol,  cedar  oil.  and 
many  allied  bodies.  Many  of  these 
alter  the  tissues;  probably  all  of 
them  do  slightly,  but  the  least  ob- 
iectionable  is  cedar  oil.  From 
absolute  alcohol  the  tissue  is  car- 
ried into  the  clearing  agent,  pre- 
ferably cedar  oil,  and,  to  make  the 
change   gradual,   the   cedar   oil    is  r        u         ■ 

diluted  with  an  equal  part  of  absolute  alcohol ;  after  twenty-four  hours 
treatment  in  this  mixture  the  tissue  is  transferred  to  pure  cedar  oil  for 


jL 


Fig.  30. 

1-lat-iron-shapcd  copper  t.ihlf.  whirh  may  tio  usc<) 

for  paraffin  infillr.i''   "  "       ■--•'- m 

of  IiKkmI  l'ilm<.      !■  :"'l 

under    t^--  ii[>    '■'  "'' 

right  '■'' 

to  a  " 

end  •  '"•« 
oft.-. 


part 
hot. 


small  luriiiin  .11-11   1-   I'l.iii'i  ">ii 
the  paraffin  is  kcpl  barely  melted. 


36 


TECHNIC. 


twenty-four  hours,  and  then  to  cedar  oil  containing  sufficient  paraffin 
to  thicken  it  perceptibly ;  twenty-four  hours  later  the  specimen  is  placed 
in  melted  paraffin,  the  melting-point  of  which  should  be  50°  C.  in  summer 
and  45°  C.  in  winter.  The  paraffin  must  be  kept  as  near  the  melting- 
point  as  possible  by  means  of  a  paraffin  oven  and  a  thermoregulator. 
After  from  six  to  twentv-four  hours  the  tissue  is  transferred  to  fresh 


Fig.  31. 
block  of  hard  wood  or  of  rubber  fiber  as  usual 
received  in  the  laboratory. 


Same  block  as  figure  31,  with  corners  properly 
trimmed  to  receive  paraffin  or  celloidin  for 

embedding. 


Fig.  33. 
Method  of  applying  paper  to  block. 


paraffin  at  the  same  temperature,  in  which  it  is  kept  from  twelve  to 
twenty-four  hours.  The  gentle  heat,  continuously  applied,  displaces 
the  cedar  oil  and  permits  the  paraffin  to  infiltrate  the  interstices  of  the 
tissues.  One  end  of  a  wooden  block — about  a  two-centimeter  cube — is 
warmed  over  a  Bunsen  burner  and  dipped  in  the  melted  paraffin.  It  is 
then  wrapped  with  a  strip  of  paper  four  centimeters  wide,  so  that  the 


HISTOLOGIC    METHODS. 


paper  projecting  from  the  warmed  and  toated  end  ot"  the  bhxk  forms  a 
well  deeper  than  the  tissue  to  be  mounted.  The  l^lock  of  tissue  is  then 
])laced  in  ])Osition  at  the  bottom  of  the  well,  arranged  to  eut  to  the  best 
advantage,  and  melted  parafhn  poured  in  until  the  well  is  filled.  This  is 
allowed  to  cool  and  the  ])aper  is  then  removed.  The  paratfm  is  now  gray. 
appears  granular,  and  is  said  to  be  in  the  crystalline  form;  if  put  in  a 
wami  place. — care  being  taken  that  it  is  not  warm  enough  to  melt  the 
paraffin, — it  soon  becomes  transparent,  or,  it  is  said,  the  paraHin  becomes 
amorphous,  homogeneous,  or  hyaline. 

The  block  is  now  ready  to  cut.  It  is  trimmed  down  nearly  to  the 
tissue,  each  side  being  cut  so  as  to  present  a  surface  square  to  the  knife, 
the  general  aspect  of  the  block  being  that  of  a  truncated  pyramid.  The 
])araffin  trimmed  ot^f  is  remelted,  and  may  be  used  many  times.  The 
block  is  clamped  in  the  holder  of  the  microtome  so  that  the  cutting-edge 
of  the  knife  strikes  scjuarely  against  the  block  along  its  whole  length; 


\ 

\ 

N 

A 



ir--1 

r--"  1     ^    .! 

\   ^L J\ 

> '■^ 

c 

k. 

Kk..  34.  Fig.  35- 

PArxT  (.\.  .\.  A.  .\>  proixrlv  wrapped  around  block  (C).  with  block  of  tissue  (B)  to  be  embedded,  readv  for  pouririK 
the  paratlin  in  and  comi.Uling  the  cast.  .After  the  ca.st  cools  (sec  text)  the  paixTXS  removed  and  the  parathn 
is  trimmed,  as  shown  in  litjurc  35,  carefully  avoiding  the  block  of  tissue,  which  should  be  thoroughly  covered 
by  the  paratlin  at  all  ix)ints. 

the  knife  is  so  arranged  that  it  cuts  like  a  chisel,  and  not  with  a  drawing 
motion.  To  get  the  best  sections,  the  paraffin  must  be  of  the  proper 
temperature,  as  this  determines  the  density;  in  summer  the  block  may 
have  to  be  cooled  bv  ice;  in  winter  it  may  require  warming. 

The  most  imi)ortant  factor  in  paraffin  infiltration  is  thorough  dehy- 
dration and  clearing.  Absolute  or  approximately  absolute  dehydration 
is  necessarv  in  order  to  secure  penetration  of  the  clearing  agent— cedar 
oil,  xvlol,  or  whatever  it  may  be.  If  the  pieces  of  tissue  are  small,  the 
stages  of  the  process  may  be  shortened.  Tissue  kept  too  long  in  strong 
alcohol  or  in  the  clearing  agent  or  paraffin  (warm)  not  infrequently 
becomes  brittle.  The  occurrence  of  this  condition  should  lead  the 
worker  to  shorten  the  stages  sufficiently  to  overcome  the  difficulty. 
When  osmic  acid  methods  have  been  used  for  the  purpose  of  determining 
the  presence  of  fat.  the  clearing  agent  and  paraffin  may.  under  some 


TECIINIC. 


conditions,  partly  remove  the  fat.     In  osmic  acid  preparations,  when  the 
fat  is  to  be  retained,  celloidin  infiltration  is  to  be  preferred. 

It  will  be  seen  that  the  foregoing  process  requires  days,  and  to 
overcome  this  objection  Reeves  has  recommended  the  following:  (i) 
Fix  in  saturated  alcoholic  solution  of  corrosive  sublimate  for  one  hour. 


Sf 


rifflk 


Fig.   36. — Naple's  Paraffin  Bath  for  Infiltrating  Tissues  in  Paraffin. 

The  apparatus  consists  essentiaOy  of  a  series  of  receptacles  for  holding  the  melted  paraffin,  with  a  surrounding 

water-bath  retained  at  an  even  temperature  by  a  thermoregulator. 

Bv  this  method  fixation  and  dehydration  go  on  together;  (2)  absolute 
alcohol,  one  hour;  (3)  xylol,  one  hour.  As  xylol  has  a  very  low  vol- 
atiUzing  point,  it  quickly  evaporates  in  the  paraffin  bath,  and  permits 
the  rapid  penetration  of  the  paraffin;    it  is  kept  one  hour  in  the  first 


Fig.  37.— Forceps  Convenient  for  Handling  Cover-glasses,  Blocks  of  Tissues    and  Sections. 

paraffin  and  one  hour  in  the  second,  when  it  is  cast.  In  order  to  pre- 
vent crystallization  of  the  paraffin  the  cast  is  plunged  into  ice- 
water  as  soon  as  its  surface  has  cooled  sufficiently  to  form  a  thin  film ; 
the  cooling  may  be  facilitated  by  holding  the  block  out  of  the  window 
in  winter  or  bv  gently  blowing  upon  it  in  summer.     The  cast  is  now 


MISTt)LOC,lC   MKTIIonS. 


S9 


trimmed  and  rut.  Of  course,  the  pieces  of  tissue  to  be  prepared  in 
this  way  must  he  very  small, — not  over  0.5  cm.  cube, — and  the  re- 
sults can  not  be  considered  as  comparable  to  the  slower  method  already 
described. 


Fig.  38 — Laboratory  Microtome. 
Can  be  used,  as  shown  in  the  cut,  for  celloidin  sections;   an  attachment  for  freezing  may  lie  &ul>stitule<l  for  the 
clamp  shown  in  the  illustration  immediately  below  the  knife.     For  paraffin  blocks  the  knife  must  be  turned  with 
it.<;  cutting-i-<lBf  at  a  right  angle  to  the  plane  of  the  knife-carrier. 

Moiiiitiui:,  Paraffin  Sections. — If  the  .sections  be  prof)erly  cut  and 
the  infiltration  has  been  satisfactory,  they  will  adhere  in  chains  or 
ribl)ons  as  they  come  away,  or  each  section  may  V)e  removed  from  the 
knife  as  rapidly  as  cut.  using  a  short  sable  brush  for  the  purpose.  To 
insure  thin  sections,  the  knife  must  be  of  the  utmost  sharpness.      Be- 


Fic.  30. — Small  MimosiTipir  Snssoiis. 
Suit.ible  for  trimming  sections  and  laU-N  and  for  other  micTostopic  work. 

fore  the  sections  are  cut  it  is  best  to  prepare  the  slips  to  receive  them. 
The  slips  or  slides  are  thoroughly  cleansed  with  alcohol  anfl  dried, 
using  toilet-paper  or  a  soft  cloth  for  that  purpose.  Place  on  the  cen- 
ter of  the  slide  a  very  small  quantity — less  than  a  drop — of  Mayer's 


40 


TECHXIC. 


albumin,  and  with  a  perfectly  clean  finger  wipe  it  off.  This  leaves 
an  almost  imperceptible  layer  of  the  albumin.  On  this  place  a  few 
drops  of  water, — enough  to  float  the  section  just  clear  of  the  albumin, 


Fig.    40. — RvDER  Microtome. 
Expressly  adapted  for  paraffin  sections  and  for  cutting  in  series  ;  can  not  be  used  for  frozen  sections, 
employed  for  celloidin  if  the  chloroform  method  ot  hardening  has  been  adopted. 


May  l>e 


— and  place  the  section  on  the  water;  gently  warm  the  slide,  being 
careful  not  to  melt  the  paraffin;  as  the  section  becomes  warm  it  will 
straighten  out,  all  folds  and  wrinkles  disappearing.  Now  carefully  pour 
off  the  excess  of  water,  and  the  section  falls  upon  the  layer  of  albumin. 


Fig.  41. — Ra-vvier's  Microtome. 
Blocks  of  tissue  infiltrated  with  ceUoidin  or  paraffin  may  be  cut  in  sections  free-hand  with  an  ordinary  razor;  better 
results  may  be  oVjtained  by  even  so  simple  a  microtome  as  the  above  ( Ran\-ier's  microtome)   or  very  much 
better  results  by  the  Ryder,  Minot.  or  Bausch  and  I.omb  instruments. — (Illustration  jrom  Gould's  Dictionary.) 


to  which  it  adheres.  ^Mayer's  albumin  is  composed  of  egg-albumen 
(white  of  egg)  and  glycerin,  of  each  100  c.c,  to  which  one  gram  of 
salicylate  of  sodium  has  been  added  to  aid  the  glycerin  in  preserving 


llISToI.oC.U"     MI'TIIODS. 


4J 


the  albumin;  after  tliorou^hly  mixing,  the  mass  is  filtered  throuj^h 
paper — a  process  requiring'  weeks.  The  alhumm  fixes  the  section  to 
the  slide,  so  that  it  may  be  taken  through  the  subsequent  processes 
without  danger  of  becoming  detached.  After  the  section  has  been 
drained  of  the  water  upon  which  it  was  floated  to  facilitate  flatten- 
ing, it  is  placed  in  a  drying  oven  to  get  rid  of  any  remaining  water. 
In  ordinary  work  where  no  great  haste  is  demanded  the  slide  may 
be  placed  in  some  warm  place,  protected  from  the  dust,  until  perfectly 
dry.  After  drying,  which  may  require  from  f(nir  to  twenty-four  hours, 
the  slide  is  gently  warmed  until  the  ])arafhn  just  melts,  and  no  more;  it 
is  then  thrust  into  ordinary  kerosene,  or.  what  is  slightly  better  but  much 


Fig.  43. — Mjnot  Microtomf.. 

Iwi.  -i/c-  ui  ihc  inMruni,  III    in    lu.i.ic:    the  illustration  i-  •■'  •'>■■  -'-'l'' 
al)ove  the  knife  is  inienflcfi  to  receive  the  block  of  ; 
The  writer  has  found  this  extremely  difficult  and  ic: 
catcd  orienting  attachments  shown  in  the  cut,  and  >; 
of  cementing  the  tissue  to  the  microtome. 


,1    pl.Ur    j.. 


more  expensive,  xvldl;  either  of  these  quickly  removes  the  parattin 
usuallv  requiring  about  fifteen  minutes:  wipe  oflf  the  excess  of  xylol, 
rinse  the  mount"  in  alcohol,  and  place  the  slide  in  that  liquid  unti  the 
xvlol  is  removed.  From  the  alcohol  the  section  is  stained  as  will  be 
directed  later.  If  the  tissue  was  fixed  in  a  solution  containing  mcr- 
cur\'  this  must  be  removed  bv  treating  the  section  with  tincture  o 
iodin.  in  which  it  is  immersed  for  fifteen  minutes;  it  is  then  waslicl 
with  a  few  drops  of  alcohol  and  placed  in  a  jar  of  alcohol,  from  winch 
it  i'^  removed  for  staining  when  desired.     If  tlv>  l.V..  V   ot    tissue  was 


42  TECHNIC. 

carried  through  iodized  alcohol,  the  section  need  not  be  treated  with 
the  tincture. 

2.  Celloidin  Infiltration. — Celloidin  is  a  proprietary  product  hrst  used 
in  photography,  and  is  nothing  more  than  a  nonexplosive  gun-cotton. 
As  used,  it  is  dissolved  in  equal  parts  of  alcohol  and  ether,  thus  making 
a  collodion  that,  so  far  as  the  author  can  observe,  has  no  advantage  over 
a  good  collodion  made  from  gun-cotton.  The  alcohol  used  for  this 
purpose  should  be  absolute;  the  solution  will  be  facilitated  by  placing 
the  celloidin  in  a  tightly  stoppered  bottle — a  citrate  of  magnesia  bottle 
is  to  be  recommended — and  pouring  on  the  absolute  alcohol,  which 
should  be  allowed  to  remain  in  contact  with  the  celloidin  for  twenty-four 
hours,  when  an  equal  volume  of  ether  should  be  added.     By  this  method 


Fig.  43. — Drying  Oven.  ' 
Three  tubes  for  admitting  air  to  interior.  At  D  are  three  similar 'e.xit  tubes.  B.  Shelves  upon  which  slides 
are  placed  at  the  student's  desk,  from  which,  after  labeling  each  slide  and  placing  under  the  slides  a 
piece  of  paper  with  his  name  and  desk  number,  he  places  the  tray  in  the  oven.  C.  Thermometer.  £. 
Thermoregulator.  F.  Water-gage.  G.  Cock  for  emptying  the  water  space.  The  temperature  of  the  oven 
should  never  reach  the  melting-point  of  the  paraffin,  and  had  best  be  between  37°  C.  and  40°  C. 


solution  will  be  complete  and  no  time  will  be  lost.  As  ordinarily  used, 
two  solutions  are  needed — one  a  thick,  syrupy  solution,  and  a  second  thin 
solution  made  by  diluting  the  thick  solution  with  an  equal  quantity  of 
absolute  alcohol  and  ether.  The  tissue  to  be  infiltrated  is  fixed  and  dehy- 
drated as  already  described  for  paraffin;  it  is  then  placed  for  twenty- 
four  hours  in  a  rnixture  of  equal  parts  of  alcohol  and  ether.  From  this 
the  tissue  is  transferred  to  the  thin  solution  of  celloidin.  The  l^est 
results  are  obtained  by  leaving  the  mass  for  infiltration  several  days  hi 
this  solution,  when  it  is  placed  for  an  equal  length  of  time  in  the  thick 
solution.  A  block  is  then  soaked  in  alcohol  and  ether  for  one  or  two 
hours  or  longer,  and  one  end  is  coated  with  celloidin  and  wrapped  in 
paper,  as  already  directed  for  paraffin.     Into  the  well  the  infiltrated 


HISTOLOGIC    METHODS. 


43 


piece  of  tissue  is  placed,  arranged  as  desired  for  tuiiiii^,  .iiim  tiic  ihick 
celloidin  solution  is  poured  over  it;  the  mass,  whith  is  now  said  to  be 
cast,  is  placed  under  a  lightly  fitting  bell-jar  or  cover  until  the  celloidin 
begins  to  set,  when  it  is  thrown  into  eighty  per  cent,  alcohol  fcjr  harden- 
ing. At  the  end  of  twenty-four  hcnirs  it  will  be  found  sufticiently  hard 
for  cutting,  but  it  may  be  kept  indetinitely  in  the  alcohol  and  cut  when 
desired.  Unlike  parathn,  celloidin  must  be  cut  with  the  microtome  knife 
at  an  angle  to  the  block, — that  is,  with  a  drawing  motion, — and,  while 
the  paraffin  was  cut  with  a  perfectly  dry  knife,  the  celloidin  must  be  cut 
with  a  knife  kept  flooded  with  eighty  per  cent,  alcohol.  Each  section 
is  removed  from  the  knife  as  cut  and  is  transferred  to  eighty  per  cent, 
alcohol,  in  which  it  may  be  preserved  until  wanted  for  use.  The  great 
advantage  claimed  for  celloidin  is  that,  unlike  paraffin,  it  need  not  be 
dissolved  out  before  the  section  is  stained.  Stains  such  as  carmin  and 
hematoxylin  may  be  used,  the  celloidin  holding  the  sections  together 
during  the  manipulations  incident  to  staining. 

Gilson's  Method. — A  satisfactory  method  of  celloidin  inhltration 
is  that  devised  by  Gilson,  in  which,  after  dehydration  and  treating  with 
the  alcohol  and  ether  mixture,  the  tissue  is  placed  in  a  test-tube  con- 


liKfSH    SCITABI  I 


taining  several  cubic  centimeters  of  thin  celloidin  .solution;  after  a  few 
davs  in  the  thin  celloidin,  the  test-tube  is  immersed  in  a  water-  or  par- 
affin bath  at  about  42°  C,  at  which  temperature  the  solvents  (alcohol 
and  ether)  rapidly  evaporate,  thereby  hastening  penetration  and  increas- 
ing the  density  of  the  infiltrating  mass.  When  the  solution  has  evapo- 
rated to  about  one-third  its  original  bulk,  it  is  turned  out  and  cast  as  in 
the  slow  process.  The  hardening  of  the  block  is  greatly  facilitated  and 
the  results  are  improved  by  hardening  in  chloroform.  The  chloroform 
hardening  process  is  applicable  to  blocks  that  have  been  infiltrated 
either  by  the  slow  or  by  the  rapid  method. 

As  soon  as  possil)le  after  the  cast  is  made  the  mass  is  placed  in  a 
desiccator  or  sieve  dish,  or  in  a  bottle  containing  a  teaspoonful  of  chloro- 
form and  having  a  tightly  fitting  stopper.  A  support  is  arranged  al>ove 
the  chloroform,  on  which  the  block  to  be  hardened  is  placed,  and  the 
vessel  is  then  tightly  closed.  From  two  to  twelve  hours  will  be  sufficient 
for  the  hardening,  after  which  the  block  is  placed  in  a  mixture  of  cedar 
oil  two  parts  and  chloroform  one  part;  more  cedar  oil  is  added  from 
time  to  time  until  nearly  pure  cedar  oil  is  attained.  The  sections  are 
cut  drv,  as  in  the  paraffin  method.      The  block  ni  '■eser\'ed  in- 


44 


TECHXIC. 


-GROUND  SURFflCd. 


CROSS  SECT/ON  PtQ 
SHOWING  SUD£5 
W  POSITION. 


definitelv  in  the  cedar  oil.'     After  cutting,  the  sections  are  washed  in 
alcohol  in  order  to  remove  the  cedar  oil,  and  may  then  be  stained. 

Sections  obtained  by  the  celloidin  embedding  and  infiltration  process 
may  be  secured  to  the'  slide  by  ether  vapor  or  by  a  very  thin  layer  of 
celloidin.  The  best  method  is  to  float  the  section  on  to  the  slide,  blotting 
it  carefullv  with  bibulous  paper,  and,  from  a  bottle  containing  a  small 
quantity  of  ether,  to  pour  the  vapor  upon  the  section.  This  will"  suf- 
ficientlv  soften  the  celloidin  to  make  it  adhere  to  the  slide  during  the 
subsequent  manipulation.  It  is  to  be  remembered  that  celloidin  sections 
must  be  kept  moist  throughout  the  entire  course  of  their  preparation. 
Drving  them  is,  as  a  rule,  injurious,  if  not  destructive. 

'3.  Congelation  Method. — Fresh  tissue  may  be  frozen  and  sectioned, 
but  the  best  method  is  that  of  Hamilton:  (i)  Harden;  (2)  wash  out  the 
hardening  fluid ;    (3)  place  in  sugar  solution  for  from  two  to  twenty-four 

hours ;   this  solution  is  composed 

of  two  ounces  of  sugar  dissolved 

in  one  fluidounce  of  water ;  after 
removing  from  the  syrup,  wash 
lightly  in  water  and  (4)  place  in 
mucilage  for  two  hours.  The 
tissue  may  now  be  put  on  the 
drum  of  the  freezing  microtome , 
frozen,  and  cut.  Remove  sec- 
tions from  the  knife  with  a  soft 
brush,  and  wash  them  thor- 
oughly in  water  to  remove  the 
gum  and  sugar;  the  staining  is 
proceeded  with  as  for  other  sec- 
tions. 

Remarks  on  the  Foregoing 
Processes. — For  small  pieces  of 
tissue  the  paraffin  method  is 
best;  thinner  sections  can  be 
cut,  and  the  method  of  cement- 
ing them  on  the  slide  makes  the 
handling  most  convenient.  It  is 
commonly  stated  that  large 
blocks  can  not  be  sectioned  by 
the  paraffln  method;  this  is  true  in  part  only.  A  specimen  0.5  cm.  in 
thickness  and  2  cm.  square  may  be  infiltrated  thoroughly,  and,  under 
favorable  conditions,  with  a  good  modern  microtome,  should  yield  sections 
not  over  5  //  thick,  and  in  skilled  hands  they  may  be  cut  even  thinner.  For 
large  specimens,  such  as  an  eye,  and  for  tissues  from  the  brain,  spinal  cord, 
or  larger  nerve-trunks,  celloidin  is  to  be  preferred.  After  using  the  freezing 
method  to  a  very  large  extent  for  about  ten  years,  the  author  is  thor- 
oughly convinced  that  it  is  not  to  be  relied  upon.     The  ice  crystals  that 

1  Since  the  publication  of  the  last  edition  of  this  manual  the  writer  has  known 
of  considerable  difficultv  due  to  softening  of  the  celloidin  when  preserved  in 
cedar  oil.  The  cause  of  this  unfortunate  complication  was  not  at  first  discovered. 
It  wotild  appear  that  the  success  of  the  method  depends  upon  the  quality  of  the 
cedar  oil.  Mayer  has  recently  informed  Harris  that  cedar  oil  prepared  by  Schim- 
mel  did  not  in  the  least  affect  the  celloidin. 


Fic.  45. 


L  ID  Wl  TH  E06£  GROUND 
TO  f/T  /J_ 

-Dish  for  Removing  Paraffin  and  Corrosive 
Sublimate  and  for  Dehydrating. 
May  also  be  used  for  staining,  and  for  the  same  purposes  as 
the  Stender  dish.  After  the  sections  are  cemented  on 
the  slide  the  sUdes  are  placed  back  to  back  and  shpped 
down  in  the  groove,  as  shown  at  B  at  the  bottom  of  the 
dish.  If  the  slides  are  thin,  the  dish  \n]l  hold  ten  at  one 
time. 


IIISTOLOCIC    MKTIIODS,  4;; 

form  in  freslily  frozen  tissue  break  u])  tlie  cells  and  p^'wc  results  that  may 
mislead  the  most  exjjerieneed  investigator.  The  distortion  of  structure 
incident  to  the  use  of  congelation  masses,  their  maceratinj^'  j)ro|jerties, 
and  the  difhculty  in  removing  the  infiltrate,  have  led  me  to  give  tliem 
up  entirely  for  laboratory  work;  only  the  crudest  kind  of  jjathologic 
work  can  he  performed  by  the  freezing  and  congelation  methods  at 
present  at  our  disposal,  and  the  results  are  always  oj)en  to  criticism. 

STAINING  AND  MOUNTING. 

General  Remarks.-  As  a  rule,  it  is  best  for  the  student  to  work  with 
one  stain  until  he  is  familiar  with  it;  and  l)efore  combining  two 
or  more  stains  it  is  best  for  him  to  familiarize  himself  with  the  action 
of  each  stain  when  used  alone.  The  student  thould  remember  that 
there  are  two  principles  involved  in  staining:  (i)  When  a  stain  shows 
unusual  selectivity  in  certain  bodies,  such  as  cell  nuclei,  it  is  allowed 
to  act  long  enough  to  color  the  desired  bodies  only;  its  action  is  then 
stopped  and  the  ^preparation  of  the  mount  continued.  (2)  The  stain 
is  permitted  to  act  until  everything  that  will  receive  the  color  is  stained, 
and  then  some  agent  is  ap])lied  that  differentiates  certain  elements  by 
removing  the  stain  from  other  structures.  Thus,  acid  alcohol  is  ui-ed 
to  differentiate  in  carmin  staining,  and  water  after  hematoxylin.  Alco- 
hol or  water,  either  of  which  may  be  used  with  or  without  acidulation, 
are  also  used  to  differentiate  with  the  anilin  dyes.  The  objection  to 
examining  sections  unstained  is  that  no  one  structure  is  prominent; 
and  if  everything  in  the  section  be  uniformly  colored,  nothing  is  gained 
by  the  staining.  For  this  reason  differentiation  is  more  or  less  appli- 
cable to  all  stains.  After  differentiation,  or  in  some  instances  simul- 
taneously with  this  ])rocess,  dehydration  is  necessary  in  order  to  pro- 
ceed with  the  next  step — clearing  the  section.  The  jjrocess  of  clear- 
ing is  necessary  in  order  to  examine  the  section  by  transmitted  light. 
Clearing  aLso  makes  the  a])])lication  of  a  permanent  medium,  such  as 
xylol  balsam,  possible. 

The  clearing  agents  mentioned  in  the  preceding  and  following  pages 
are  not  all  applical^le  under  all  circumstances.  The  l)est  clearing 
fluids  are  xylol,  cedar  oil,  creasote,  and  possibly  one  or  two  other  agents 
having  more  or  less  special  uses. 

Carmin  and  Hematoxylin. — The  two  stains  most  fre(]uently  used 
in  laboratory  work  are  carmin  and  hematoxylin.  Strongly  alkaline 
stains,  such  as  lithium  carmin,  are  no  longer  to  be  commended;  the 
same  is  true  of  bulk  staining.  The  car)iiiii  most  useful  in  the  labora- 
tory is  Orenacher's  alcoholic  borax-carmin: 

.  I  li  ••lii-li,    Kuril  \  I  amiiii 

Carmin  (best  No.  40). 

Borax 

Mix  thoroughly,  i)ulv«.Tizc'  in  a  mortar,  and  add  100  part-s 
of  water;  boil  for  half  an  hour:  add  an  er|ual  bulk  of  seventy 
]>er  eent.  alcohol;    .set  aside  for  one  week,  and  then  filter. 

To  stain,  add  enough  of  the  stain  to  the  section  on  the  slide  al)un- 
dantlv  to  cover  it,  and  allow  it  to  act  for  from  five  to  ten  minutes  or 


46 


TECHNIC. 


longer.     Drain  off  the  excess  of  stain,  wipe  around  the  section  with 
paper  or  soft  cloth,  and  apply  acid  alcohol. 

Acid  Alcohol. 

Hydrochloric  acid i  part. 

Water, 29  parts. 

Alcohol ' 70 

The  section,  as  soon  as  the  acid  alcohol  is  applied,  turns  from  a 
purpHsh-red  to  a  light  crimson,  and  becomes  more  nearly  trans- 
parent; it  is  then  washed  in  strong  alcohol,  the  excess  wiped  from 
around  the  section,  and  the  latter  is  covered  with  creasote.  The  alcohol 
dehydrates  and  removes  the  acid,  which  is  the  differentiating  agent, 
and  the  creasote  renders  the  section  clear  for  examination  by  trans- 
mitted light.  As  soon  as  the 
section  is  clear  remove  the  excess 
of  creasote,  apply  a  drop  of  balsam, 
and  cover  with  a  thoroughly 
cleansed  cover-glass;  label  the 
section.  It  will  now  keep  in- 
definitely. 

One  of  the  best  carmin  stains 
is  Mayer's  carmalum.  This  is 
made  by  dissolving  i  gm.  of  car- 
minic  acid  and  10  gm.  of  alum  in 
200  c.c.  of  distilled  water,  using 
heat  if  necessary.  In  order  to 
preserve  the  solution  add  o.i  per 
cent,  of  salicyhc  acid,  or  0.5  per 
cent,  of  salicylate  of  sodium.  The 
solution  is  clarified  by  decanting 
or,  better,  by  filtration.  The  great 
advantage  of  this  solution  lies  in  the  fact  that  it  is 
almost  impossible  to  overstain  with  it,  and  by  careful 
washing  and  differentiation  practically  all  interme- 
diate degrees  of  staining  can  be  obtained.  It  may 
be  differentiated  in  acid  alcohol,  as  already  directed 
for  borax-carmin,  or,  if  the  alcohol  used  for  the  sub- 
sequent dehydration  be  strongly  tinted  by  the  addition  of  picric  acid, 
the  combined  action  of  the  two  stains  (the  carmin  being  a  nuclear  stain 
and  the  picric  acid  a  protoplasmic  stain)  will  afford  one  of  the  best 
general  stains  found  in  the  laboratory.  Picric  acid  may  be  used  in 
the  same  way  with  borax-carmin,  but  the  result  is  not  so  satisfactory. 
Hematoxylin  Staining. — The  classic  form  of  this  stain  is  Dela- 
field's,  made  as  follows:  Dissolve  4  gm.  of  hematoxylin  crystals  in  25  c.c. 
of  strong  alcohol;  add  this  solution  to  400  c.c.  of  a  cold,  filtered,  satu- 
ratec'  -aqueous  solution  of  ammonia  alum;  expose  to  light  and  air  for 
several  day  Filter,  and  add  glycerin  100  c.c.  and  methyl  alcohol 
100   c.c. 

Allowed  to  stand  in  the  light,  with  the  bottle  loosely  corked,  this 
mixture  turns  dark  purple,  almost  black;  it  should  then  be  filtered  and 
kept  in  tightly  stoppered  bottles.  For  use  it  should  be  much  diluted: 
the  amount  of' dilution  must  be  determined  for  each  lot.  varying  with  the 


Fig.  46. —  Dropping- 
bottle  with 
Barnes's  Dropper, 
Which  Closes 

THE  Mouth  of 
THE  Bottle  Like 
A  Rubber  Stopper. 

These  bottles  are  usually 
of  one  ounce  capa- 
city, and  are  con- 
venient for  holding 
stains  and  staining 
reagents. 


Fig.  47.  — Proper  Size 
Labels  for  Label- 
ing '  Microscopic 
Slides. 


HISTOLOGIC   MKTIIODS.  4- 

dcgree  of  oxidation  ami  with  the  aj,'e  of  the  stain.  If  made  with  distilled 
water,  and  provided  tliat  all  vessels  and  containers  are  kejjt  chemically 
clean,  this  stain  will  keep  for  years.  The  objection  to  this  stain  lies  in 
the  fact  that  it  requires  time  for  ripening,  and  hence  cannot  be  made  antl 
used  at  once.  Harris  overcame  this  difficulty  by  artificially  oxidizing 
the  hematoxylin  into  hematein.  Harris's  hematoxylin  is  jTrepared  bv 
dissolving  one  gram  of  hematoxylin  in  lo  c.c.  of  alcohol  and  adding  the 
resulting  solution  to  200  c.c.  of  distilled  water  in  which  20  gm.  of  am- 
monia or  potassium  alum  have  previously  been  dissolved.  The  tlui<l  is 
placed  in  a  flask  and  rapidly  heated  to  boiling,  at  which  time  i  gm.  of 
mercuric  oxid  is  added.  The  solution  at  once  darkens  (ripens)  and 
should  be  rapidly  cooled  in  running  water;  the  stain  is  now  ready  for 
use,  but  should  be  diluted.  From  this  stock  solution  an  acid  glychcBtu- 
alum  may  be  prepared  by  adding  4  c.c.  of  glacial  acetic  acid  and  30 
c.c.  of  glycerin  to  70  c.c.  of  the  stock  hematoxylin  solution.  This  acid 
hematoxylin,  strongly  resembling  Ehrlich's  acid  hematoxylin  and  Maver's 
acid  hemalum,  has  the  great  advantage  that  it  is  almost  impossible  to 
overstain  with  it. 

To  use  the  hematoxylin  of  Delatield  or  Harris  the  sections  cemented 
on  the  side,  as  already  directed,  or  in  the  case  of  celloidin  loose  sections, 
are  covered  with  the  diluted  stain  for  from  five  to  fifteen  minutes, 
washed  in  water,  dehydrated  in  alcohol,  cleared  with  creasote,  and 
mounted  in  balsam  as  directed  in  the  last  steps  for  carmin,  except  that 
differentiation  is  secured  by  the  use  of  w^ater,  and  not  by  acid  alcohol. 
A  better  stain  is  secured  by  taking  enough  distilled  water  in  a  bottle  or 
staining  dish  to  immerse  the  slide  on  end;  to  this  add  sufficient  hema- 
toxylin to  tinge  the  water  rather  deeply;  the  sections,  cemented  on  the 
slide,  are  left  in  this  overnight  (or  even  for  twenty-four  hours),  washed 
in  water,  and  treated  as  previously  directed.  Hematoxylin  not  only 
stains  the  nucleus,  but  affords  a  light  tint  to  the  protoplasm  as  well. 
This  latter,  however,  can  be  better  secured  by  using  eosin.  After  the 
section  is  stained  in  hematoxylin  and  washed  in  water,  the  excess  of  the 
water  is  removed  and  the  section  is  treated  for  a  moment  in  an  alcoholic 
solution  of  cositi  (0.5  per  cent.)  followed  by  alcohol  and  creasote,  and  is 
then  mounted  in  l)alsam.  The  nuclei  are  stained  purple  by  the  hema- 
toxylin and  the  cell  [)rotoplasm  pinkish  by  the  eosin.  This  makes  a  very 
fair  contrast  stain,  and  brings  out  some  elements  not  shown  by  the  hema- 
toxylin. In  addition,  it  shows  red  Idood-corpuscles  to  advantage,  being 
a  specific  stain  for  hemoglobin.  Picric  acid  may  l)e  usetl  with  hematoxy- 
lin to  advantage,  particularly  if  the  sections  are  a  little  thick  or  if  they 
are  overstained  in  the  hematoxylin.  After  washing  the  hematoxylin 
stain  thoroughly  in  distilled  water,  the  sub.sequent  dehydration  is  ac- 
complished by  the  use  of  alcohol  containing  a  trace  of  picric  acid.  The 
nuclear  stains  ol>tained  by  this  method  are  sharp,  and  the  •■  "  •  di 
protoplasmic  tints  are  beautifully  transparent. 

For  routine  work  I  am  unfamiliar  with  any  contrast  s»  o 

that  suggested  In-  Van  Gieson.     Various  strengths  ha\  ■ 
mended,  but  the  following,  which  may  be  further  diluted  wiih  picric,  acid 
if  necessary,  will  be  found  satisfactory: 

Van  GUton't  Solution. 
Acidfuchsin,  r  percent,  aqueous  solution. . 
Picric  acid,  saturated  aqueous  solution,  . 
Water. . 


48  TECHNIC. 

Sections  are  stained  deeply  with  hematoxylin,  washed  in  water,  treated 
with  the  above  solution  for  from  one  to  four  or  five  minutes,  rapidly 
dehydrated,  cleared,  preferably  in  xylol,  and  mounted  in  xylol  balsam. 
The  connective  tissue  is  red  or  pinkish-red,  the  cell  protoplasm  of  a  yellow- 
ish tinge,  and  the  nuclei  a  dark  brownish  or  reddish-purple.  In  properly 
fixed  preparations  containing  nerve-fibers  the  axis-cylinders  stain  red. 
Anilin  Dyes. — In  addition  to  the  use  of  these  agents  for  staining 
bacteria,  thev  have  become  important  and  useful  adjuvants  in  certain 
microchemic  reactions,  which  will  be  referred  to  under  special  headings 
throughout  the  book;  and  also  for  general  stams.  For  practical  pur- 
poses the  anilin  dyes  may  be  divided  into  two  groups: 

1.  Basic  group,  in  which  the  staining  property  is  due  to  the  base 
present  in  the  compound. 

2.  Acid  group,  in  which  the  staining  property  is  due  to  the  acid 
principle. 

The  basic  colors  are,  as  a  rule,  sharp  nuclear  stains,  while  the  acid 
dyes  stain,  more  or  less  diffusely,  the  protoplasm  in  the  cell.  As  a  rule, 
the  dyes  are  used  as  concentrated  solutions  (i)  in  water;  (2)  in  five  per 
cent,  carbolized  water;  (3)  in  thirty  to  sixty  per  cent,  alcohol,  preferably 
about  fifty  per  cent.  Under  some  conditions  the  dyes  seem  to  act  best 
if  the  solutions  are  rendered  faintly  alkahne;  or  at  other  times,  faintly 
acid.  The  alkalinity  is  usually  secured  by  the  addition  of  a  very  small 
quantity  of  carbonate  of  potassium,  and  the  acidity  by  an  extremely 
dilute  solution  of  acetic,  formic,  or  hydrochloric  acid.  The  basic  anihn 
dves  commonly  used  are  safranin,  fuchsin,  methylene-blue,  thionin, 
eentian-violet,  toluidin-blue,  etc.  The  acid  stains  mostlv  used  are  eosin, 
orange  G,  acid  fuchsin,  etc. 

The  following  formulas  and  methods  are  introduced  as  examples,  and 
after  the  student  has  familiarized  himself  with  the  technic  given,  he  may 
applv  the  knowledge  so  obtained  to  staining  with  other  and  similar 
anilin  dyes.' 

Safranin  is  a  most  excellent  nuclear  stain.  The  following  formulas 
are  to  be  recommended : 

Saturated  solution  of  safranin  in  water,  heated  to  75°  C. ;  after 
thorough  saturation,  filter;  stain  from  two  to  five  minutes  to  twenty- 
four  hours,  depending  upon  the  tissue,  length  of  fixation,  etc. ;  wash  in 
water,  differentiate  and  dehydrate  simultaneously  in  alcohol,  clear  in 
xylol,  and  mount  in  xylol  balsam.  A  mixture  composed  of  one  part  of 
the  above  solution  of  safranin  and  one  part  of  a  saturated  alcoholic 
solution  of  alcohol-soluble  safranin  makes  a  satisfactory  stain,  and  may 
be  used  in  the  same  way. 

Methyl-violet. — One  or  two  per  cent,  solution  in  water.  Stain  from 
two  to  five  minutes  or  longer,  and  treat  in  the  same  manner  as  already 
given  for  safranin. 

Polychrome    Methylene-Blue-  (Unna)  is  a  most  acceptable  stain  for 

1  One  of  the  great  difficulties  with  anilin  dyes  is  the  inconstancy  of  their  com- 
position and  the  unreliability  of  many  samples  placed  on  sale.  For  this  reason 
it  is  recommended  that  in  purchasing  the  anilin  dye  the  student  should  always 
specify  the  make  of  Griibler. 

2  This  stain  resembles,  when  diluted,  Lofller's  alkaline  methj-lene-bhie,  the 
formula  of  which  is  as  follows: 

Saturated  alcoholic  sokition  of  methylene-blue 30  c.c. 

Potassium  h3^drate  (o.oi  percent,  aqueous  solution),.  .    100  c.c. 
Mav  be  used  for  staining  tissues,  but  is  more  useful  in    bacteriologic  work. 


HISTOLOGIC    MIvTHOI)^ 

routine  laboratory  work.  Although  the  formula  i"r  iiiaKin;;  ims  ny  i 
easil)'  accessible,  satisfaction  can  best  be  obtained  by  jjurchasin^'  the 
})repared  stain  from  Grubler.  ( )ne  ])art  of  the  dye  to  two  or  three  parts 
of  water  is  the  best  strength.  Sections  shoukl  be  stained  for  fifteen 
minutes  to  several  hours,  washetl  in  water,  dehydrated,  cleared  in  xylol, 
and  mounted  in  balsam.  The  most  beautiful  results  are  obtained  by 
glvcerin-ether  or  styrone  differentiation,  both  of  which  are  described 
below.  Contrasts  with  eosin  may  be  obtained  by  staining  in  a  o.i  per 
cent,  aqueous  solution  of  water-soluble  eosin;  wash  lightly  with  water 
and  transfer  to  the  polychrome  blue;  the  latter  tends  to  remove  the 
eosin,  and  hence  success  depends  on  accurately  judging  the  time  neces- 
sary for  immersion  in  the  polychrome  solution.  Nothing  but  patient 
experimentation  can  accurately  inform  the  beginner,  but  success  rej)ays 
him  U)r  the  time  and  labor  expended. 

Toluidin-blue. — Dissolve  one  part  of  the  dye  in  loo  parts  of  a  five 
per  cent,  solution  of  carbolic  acid  in  water;  stain  from  hve  to  ten  minutes 
to  twenty-four  hours,  differentiate  and  dehydrate  in  alcohol,  clear  with 
cedar  oil,  and  mount  in  xylol  balsam. 

Ziehl's  Carbolfuchsin. — Rub  up  i  gm.  of  powdered  fuchsin  with  lo 
c.c.  of  alcohol  in  a  glass  mortar;  dissolve  5  gm.  of  crystalline  carbolic  acid 
in  100  c.c.  of  distilled  water;  mix  the  tw^  solutions  and  the  stain  is  ready 
for  use.  The  stain  may  be  prepared  by  the  addition  of  10  c.c.  of  a 
saturated  alcoholic  solution  of  fuchsin  to  90  c.c.  of  a  five  per  cent, 
aqueous  solution  of  carbolic  acid.  Stain  sections  two  to  five  minutes  to 
several  hours;  differentiate  and  dehydrate  in  alcohol,  clear  in  clove  oil 
or  xylol,  and  mount  in  xylol  balsam. 

As  a  rule,  sharpness  of  nuclear  stain  is  obtained  by  overstaining, 
followed  bv  careful  differentiation,  which  must  be  stopped  at  a  certain 
time;  the  best  results  are  obtainable  after  repeated  experiments  and 
manv  failures.  Alcohol  as  a  differentiating  agent  does  not  give  the  best 
results,  nor  is  the  differentiation  in  alkaline  or  faintly  acidulated  water 
ideal.  Two  of  the  most  satisfactory  differentiating  agents  with  which 
the  writer  is  familiar  are  glycerin-ether  and  styrone. 

The  glycerin-ether  mixture  (Unna)  is  obtained  from  Grubler;  the 
proper  dilution  is  one  part  of  the  agent  to  fifteen  of  water.  Sections 
are  stained  rather  deeply  in  Unna's  polychrome  methylene-blue  or  in 
carbol-toluidin-blue,  rinsed  in  w^ater,  and  covered  with  the  diluted 
glvcerin-ether  mixture.  At  first  the  dye  comes  out  in  clouds;  later, 
differentiation  progresses  more  slowly.  The  exact  point  at  which  to 
arrest  the  differentiation  can  be  learned  by  experience  only.  In  order 
to  arrest  the  action  of  the  glycerin-ether  the  excess  is  poured  off,  the 
section  washed  in  water  followed  by  rapid  dehydration  and  clearing  in 
xvlol  or  cedar  oil,  and  finally  balsam.  Many  bacteria  are  beautifully 
stained  bv  this  method. 

Styrone  is  a  solid,  camphor-like  body  at  a  low  temperature;  at  the 
ordinarv  room-temperature  it  assumes  a  syrupy  consistence.  It  is  a 
differentiating  fluid  that  also  acts  as  a  clearing  agent  and  is  superior 
to  other  differentiating  agents  in  that  the  tissues  may  be  watched  under 
the  microscope  without  a  cover-glass,  during  the  process  of  differentia- 
tion. In  order  to  aj>ply  it,  the  section,  stained  as  already  advised  for 
glvcerin-ether.  is  hastily  washed  in  water,  followed  by  alcohol,  and  the 
stvrone  is  at  once  applied.     The  styrone  first  applied  becomes  cloudy. 


5° 


TECHNIC. 


deeply  dyed,  and  is  poured  off;  fresh  styrone  is  added,  and  the  shde 
is  placed'  on  the  stage  of  the  microscope.  As  soon  as  the  differentia- 
tion has  become  satisfactory  the  styrone  is  washed  off  with  cedar  oil, 
the  application  of  the  latter  agent  being  continued  until  all  differentia- 
tion has  ceased ;  the  cedar  oil  is  then  removed  and  xylol  balsam  and 
a  cover-glass  are  apphed.  In  clearing  sections  stained  by  basic  anilin 
dyes  disaster  commonly  follows  the  application  of  creasote.  Xylol  is 
considerably  better,  but  the  best  results  are  obtained  by  the  use  of  cedar 
oil,  which  acts  slowly  and  must  be  given  time;  gentle  warming  hastens 
the  clearing-,  but  is  rarely  necessary  if  the  dehydration  has  been  complete. 

Eosin  may  be  used  with  either  of  the  nuclear  stains  previously  given. 
It  is  particularly  useful  with  the  toluidin-blue.  Eosin,  either  as  a  satu- 
rated solution  in  water  of  the  form  soluble  in  that  medium  or  saturated 
solution  of  eosin  in  alcohol,  using  the  form  soluble  in  that  agent, 
may  be  used  as  contrast  stains  before  or  after  the  toluidin-blue  or 
methylene-blue ;  as  both  of  these  agents  are  discharged  by  eosin  solu- 
tions, it  is  possibly  better  to  stain  first  with  eosin,  rinse  in  water,  and 
apply  the  nuclear  stain  afterward.  If  the  eosin  be  used  after  the  nu- 
clear stain,  it  should  not  be  allowed  to  act  too  long,  otherwise  the  nuclear 
stain  may  be  discharged.  As  eosin 'acts  as  a  differentiating  agent, 
when  used  after  the  nuclear  stain,  care  and  experience  are  necessary  to 
secure  the  best  results.  After  the  use  of  eosin,  dehydration  in  alcohol 
and  clearing  in  cedar  oil  are  recommended. 

For  the  use  of  eosin  as  a  contrast  stain  with  hematoxylin,  see  page 
47.  For  the  use  of  picric  acid  for  the  same  purpose  and  with  carmin, 
see  page  46. 

THE  MICROSCOPE. 

A  Desirable  Laboratory  Microscope. — Figure  48  illustrates  a  stand 
useful  in  a  pathologic  laboratory.  The  horseshoe  base  gives  solidity 
by  its  long  arms  and  great  weight.  To  this  base  is  attached  the  upright, 
which  supports  the  superstructure;  the  stand  should  be  handled  by 
this  piece  entirely,  never  grasping  the  parts  above  in  moving  the 
microscope,  as  such  a  procedure  is  hkely  to  injure  the  adjustments. 
At  the  upper  termination  of  the  upright  is  the  joint  for  inclining  the 
microscope  for  convenience  in  working.  Running  to  the  front  from 
this  joint  is  the  stage  upon  which  the  slide  is  placed  for  examination; 
clips  are  shown  for  retaining  the  slide  in  position.  Beneath  the  stage 
are  the  substage  mountings,  consisting  of  diaphragms  for  lessening 
the  hght,  condenser  for  increasing  the  rays'  intensity,  and  a  mirror 
for  reflecting  the  light  upward  through  the  optic  axis  of  the  instrument. 
These  parts  are  adjustable  by  lateral  movement,  by  rack,  pinion,  and 
screw  motion.  Behind  the  inclination  joint,  and  above  the  stage,  what 
is  known  as  the  upright  arm  rises;  at  its  upper  part  is  placed  the 
fine  adjustment,  worked  by  a  milled  thumb-screw.  Passing  off  in  front 
of  this  upright  arm  is  the  horizontal  arm,  to  which  is  attached  the 
coarse  adjustment  by  rack  and  pinion  moved  by  the  milled  heads 
shown  at  both  sides.  The  tube  carrying  the  optic  parts  is  attached 
to  the  horizontal  arm  by  the  rack  and  pinion  coarse  adjustment.  The 
tube  is  so  made  that  it  may  be  drawn  out  to  a  standard  length.  At 
the  upper  end  of  the  tube  is  the  eye-piece;    at  the  lower  end,  the  objec- 


HISTOLOGIC    MKTIIonS. 


live.  In  the  laboratory  instrument,  when,  for  any  reason,  an  oil-im- 
inersion  objective  may  not  be  desired,  two  objectives  (a  1(  of  an  inch 
and  a  \  or  ,;  of  an  inch)  are  mounted  on  a  double  nose-piece,  l)y  means 
of  which  either  objective  may  be  brought  into  vise.  In  bactcriologic 
examinations  in  which  an  oil-immersion  lens  is  indispensable,  three 
objectives  are  mounted  on  a 
triple  nose-piece,  as  shown  in 
the  cut.  (Fig.  48.)  In  nearly 
all  cases  the  examination  should 
bcgiti  with  the  lower  power,  fol- 
lowed. //  )icccssary.  In-  the  higher 
power. 

To  Use  the  Microscope. — The 
instrument    is   placed    in    front 
and  slightly  to  one  side — usually 
the  right  side — of  the  observer; 
the  student  is  advised  to  use  the 
instrument  with  the  stage  hori- 
zontal,   that    is.    without   using 
the    inclination    joint.      During 
the  day,  northern  light  or  light 
from  white  clouds  is  preferable ; 
if  the  window  is  exposed  to  the 
direct  rays  of  the  sun.  a  piece 
of    thin   tissue-paper   is    pasted 
over  the  glass,  or  the  glass  may 
be  frosted  or  painted ;  direct  sun- 
light should  never  be  used  ex- 
cept for  photomicrography.    If 
an  artificial  light  is  to  be  used, 
the  microscope  is  placed  about 
thirty     centimeters     from    the 
light,  and  to  one  side,  so  that 
neither  the  heat  nor  the  direct 
rays  from  the  light  will  be  thrown 
in  the  face  or  eyes  of  the  ob- 
server.    The  best  artificial  light 
is    afforded    by    the    Welsbach 
burner  or  a  thirty-two  candle- 
power  incandescent  burner  with 
a     thoroughly     frosted     globe. 
While  for  convenience  in   gen- 
eral  work    the   stand    may   be 
tilted,  when  examining  mounts 
of   liquids,   urine,  hanging-dro]^ 
culture,    etc..    the    stand    must 
be    upright    so    that    the    .stage 
is    perfectly    level.      Place    the 

slide  on  the  stage  and  looselv  secure  it  by  the  clips;  so  adjust  the  mirror 
as  to  illuminate  the  center  of  the  held ;    without  placing  the  eye  • 
eve-piece,  rack  the  objective  down  until  it  almost  touches  the 
then  look  into  the  instrument  and  perfect  the  illumination  by  adjust- 


I'lG.    4S.- 


-MlCR,  hLK      >OR    CiFNKRAL    PATHO- 

LOGIC   ANU    Ba^-IERIOLOCIC    Work. 

Draw-lubf.      c.    Rack,     d 


a.  (Jcular     or    eye-piece,     h. 

Milled  head  of  pinion  nrnving  ttv   -•  \-    <> 

pinion  (c  and  J)  toRithcr  .ire  i 

mcnt.     e.  Miirosropic  ml" 

wiiich    the    line    adjust tn   ■  - 

nose-piece   or   revolver 

h:   in  Ihe  alxjve   instrut- 

which  in  turn  may  lie  t 

»'.  Stage  on  the   upjx-r 

holding   the    «liil.-   dtiri' 

phragm  in      '    ' 

variation   ii 

fondcns<r  • 

a  mined. 

den.scr  anil 

lie  thrown  • 

into  tV 

joint 

vcrti 

the   piii.it    ,111.1   1-   "M ) •■-    

horseshoe  base  supporting  the  iiMtnimcnt 


md 


52  TECHNIC. 

ing  the  mirror  again,  if  necessary;  slowly  focus  upivard  by  the  coarse 
adjustment  until  a  satisfactory  focus  is  obtained;  in  moving  the  slide 
about,  the  line  adjustment  alone  is  required.  Never  focus  downward 
until  you  have  mastered  the  method  just  given;  careless,  or  even  at 
times  the  most  careful,  downward  focusing  will  crush  the  slide  or  the 
lens  by  passing  over  the  true  focus  and  jabbing  the  objective  into  the 
slide.  Before  removing  the  slide,  always  rack  the  objective  upward  until 
it  is  at  least  i  cm.  from  the  slide. 

To  use  the  -^^  i^ich  oil-immersion  objective;  First,  itith  a  lower  power, 
accurately  center  some  object  in  the  field  upon  which  to  focus;  rack 
the  tube  upward  until  the  objective  is  four  or  live  centimeters  from 
the  slide;  rotate  the  nose-piece  so  that  the  yV  inch  objective  drops 
into  the  optic  axis  of  the  instrument.  Erect  the  stand  so  as  to  make 
the  stage  level.  Place  on  the  cover-glass  a  drop  of  cedar  oil,  at  such  a 
point  that  when  the  objective  is  racked  down  it  will  touch  the  drop  of 
cedar  oil  at  its  center.  The  objective  is  now  lowered  into  the  cedar 
oil;  looking  into  the  instrument,  adjust  the  light  so  that  the  field  is 
well  illuminated,  the  light  uniformly  distributed,  but  not  too  brilliant 
or  glaring;  this,  if  present,  should  be  overcome  by  closing  the  iris  dia- 
phragm until  a  soft,  even  illumination  is  obtained.  Now,  with  the 
fine  adjustment,  slowty  focus  upward  but  one  or  two  turns  of  the 
milled  head;  the  object  should  come  into  view.  If  it  is  indistinct  or 
hazy,  try  readjusting  the  iris  diaphragm  or  the  light,  or  the  Abbe  con- 
denser may  be  moved  downward  or  upward  until  the  desired  effect  is 
secured.  In  examining  stained  preparations  the  iris  diaphragm  is  kept 
open;  for  unstained  specimens  it  is  choked  down,  admitting  but  little 
light.  The  successful  study  of  any  specimen  is  largely  dependent  upon 
securing  perfect  adjvtstment  of  all  parts  of  the  microscope,  and  particularly 
the  illumination.  In  case  the  field  fails  to  clear  up  after  careful  ad- 
justment of  the  instrument,  examine  the  lenses  to  see  that  they  are 
not  dirtv. 


PART  11. 
GENERAL  PATHOLOGY 


PART  ll.-GENERAL  PMHOLOGY. 


INTRODUCTION. 

Pathology  bears  the  same  relation  to  a  jiroper  study  oi  disease  that 
phvsiologv  does  to  a  knowledge  of  those  eomplieated  phenomena  the 
sum  total  of  which  is  called  hfe.  Physiology  deals  with  the  normal 
processes, — the  functions  of  organs  and  tissues  in  health, — while  jjathol- 
ogy  is  a  study  of  the  causes  and  manifestations  accompanying  disease. 
Physiology  is  the  science  of  normal  life;  pathology  is  the  science  of 
abriormal  life — disease.  It  has  been  said,  and  quite  truly,  that  pathol- 
ogy is  morbid  physiology — the  physiology  of  disease.  The  two  sub- 
jects demand  associated  study,  as  from  a  knowledge  of  one  is  acquired 
more  or  less  information  bearing  either  directly  or  indirectly  upon 
the  other.  A  detailed  study  of  the  intricate  problems  of  morl)id  proc- 
esses, and  of  the  relations  of  tissue  change  to  alteration  of  function, 
and  a  thorough  acquaintance  with  the  normal,  render  at  once  apparent 
the  intimate  association  of  pathology  and  physiolog)'. 

Throughout  the  study  of  pathology  it  is  to  be  remembered  that  the 
changes  contemplated  are  but  perversions  of  the  normal.  Disease, 
with  its  alterations  in  structure  and  function,  is  not  an  entity  from 
without,  not  an  importation  whose  existence  within  the  body  is  passive, 
but  all  morbid  processes,  while  they  may  arise  from  causes  acting  from 
without, — causes  having  an  existence  as  a  part  of  the  outside  world 
properly  so  called, — are  themselves  essentially  but  perversions  of  nor- 
mal vital  activity.  The  same  cells,  or  their  progenitors,  active  in  a 
morbid  process,  were  the  essential  elements  in  the  normal  life  of  some 
tissue  of  the  body.  As  the  result  of  altered  conditions  the  cellular 
activity  has  been  perverted,  and  the  new  line  of  cell  life  is  but  a  change 
in  the'  manifestations  of  cellular  activity — not  a  new.  nor  foreign, 
nor  extraneous  life  carried  on  within  the  affected  tissues.  The  apparent 
exception  to  this,  in  the  growth  of  animal  and  vegetable  parasites 
within  the  tissues,  is  not  really  an  exception;  so  long  as  the  life  of  the 
normal  cells  is  not  in  any  way  disturbed,  disease  does  not  result;  as 
soon,  however,  as  the  foreign  elements  interfere  with  the  usual  course 
of  events,  those  cells  performing  certain  functions  in  a  manner  recog- 
nized as  normal  for  the  species  under  ol)servation  assume  a  new  rAIe. 
and  manifest  their  activity  along  a  line  foreign  to  their  usual  course. 
It  therefore  becomes  evident  that  the  diseased  tissue  is  the  result  of 
changes  in  the  normal,  and  that  the  cellular  elements  present  are  but 
modified  forms  of  normal  cells.  In  order  properly  to  appreciate  the 
significance  of  tissue  alterations  a  careful  investigation  into  the  causes 
of  disease  becomes  an  absolute  necessity;  with  advance  in  the  study 
of  etiology  it  has  l)ecome  possible  to  comprehend  many  diseases  and 
other  phenomena  previously  inexplicable. 

The  study  of  the  active  process  associated  with  disease  and  its  re- 


56  GEXERAL    PATHOLOGY. 

suits  implies  the  investigation  of  gross  alterations — the  morbid  anatomy  ; 
and,  what  is  truly  included  as  a  part  of  the  anatomy,  the  changes  in 
the  finer  structure  of  the  tissues — the  morbid  histology.  That  the  study 
of  these  two  divisions  of  the  subject  may  have  important  bearing  on 
practical  medicine  it  is  necessary  to  observe  the  relation  maintained 
between  both  gross  and  microscopic  lesions  and  the  function  of  the 
diseased  organ;  this  constitutes  a  study  of  morbid  physiology,  the 
perversion  of  the  normal,  due  to,  or  associated  with,  the  lesions,  either 
gross  or  microscopic,  themselves  the  active  phenomena  of  disease;  and, 
lastly,  the  pathologist  must  be  familiar  with  the  results  following  the 
subsidence  of  morbid  processes. 

In  the  youth  of  medicine  scientific  classification  of  disease — no- 
sology— was  even  more  difficult  than  now;  names  were  applied 
because  they  fitted  certain  symptoms,  little  was  known  as  to  the 
intimate  nature  of  morbid  processes,  and  superficial  phenomena  consti- 
tuted the  basis  upon  which  practically  all  diseases  were  grouped.  The 
labels  derived  from  clinical  study  alone  were  often  totally  inadequate 
and  frequently  brought  into  a  heterogeneous  mass  diseases  having, 
possibly,  but  one  symptom  in  common;  thus,  for  over  twenty  cen- 
turies, decade  by  decade,  the  mass  of  "fevers"  has  been  robbed  one  by 
one  until  each  member  of  the  group  has  been  appropriately  ticketed 
and  placed  in  its  proper  nosologic  position.  This  statement  is  not  to 
be  construed  too  strictly,  lest  it  smack  of  finality,  and,  as  Ballantyne 
wisely  observes,  finalism  is  obnoxious  to  the  scientific  mind.  There 
can  be  no  doubt  that  our  present  conception  of  man}^  febrile  processes 
must  be  modified  as  our  knowledge  advances ;  whenever  science  attains 
a  new  height  an  additional  lode  is  opened  and  the  whole  field  of  view 
is  extended.  With  the  widened  horizon  old  ideas  take  on  new  colors 
and  previously  mapped  areas  must  again  be  resurveyed  and  adapted 
to  newlv  discovered  facts.  For  these  reasons  pathology  lacks  the 
stability  of  anatomy,  and,  like  physiology,  must  frequently  readjust 
itself  to  freshly  acquired  knowledge;  the  theory  of  air-borne  malaria 
fails  as  transmission  by  mosquitos  is  established,  sleeping  sickness  is 
transferred  to  diseases  produced  by  animal  parasites,  and  in  the  dark- 
ness enveloping  our  knowledge  of  even  syphilis  and  cancer  there  is 
promised  light.  Investigation  constantly  extends  the  boundaries  of 
truth,  and  the  theory  of  yesterday  falls  before  the  revelation  of  to-day. . 

The  methods  of  pathologic  research  by  which  new  truths  are  ac- 
quired must  of  necessity  vary  with  the  morbid  process  under  considera- 
tion. When  any  of  the  lower  animals  are  susceptible  to  the  disease 
under  investigation,  for  evident  reasons  the  experimental  method 
offers  many  advantages.  Being  able  to  vary  the  conditions  under 
which  disease  is  induced  in  an  animal,  to  kill  the  animal  at  any  period 
in  the  development  of  the  morbid  process,  and  more  fully  to  control 
external  conditions,  make  this  method  in  many  instances  of  the  greatest 
value. 

Like  all  methods  for  studying  disease,  animal  experimentation  is 
open  to  certain  objections;  it  is  not  possible  in  all  cases  fully  to  interpret 
the  results,  or  they  may  not  be  applicable,  on  the  whole,  to  man.  Again, 
many  diseases  to  which  man  is  liable  can  not  be  induced  in  animals, 
and  in  such  cases  the  method  fails.  While  such  important  objections 
to  the  method  often  hold  true,  the  author  does  not  recall  a  single  in- 


INTRODUCTION. 


it 


Stance  in  which,  alter  prolonged  efYort,  it  has  not  been  possible  to  learn 
something,  and  in  a  number  of  diseases  the  method  under  consideration 
has  afforded  full  and  entirely  satisfactory  exi)lanation  of  phenomena 
previously  obscure  or  absolutely  unapi)reciated.  In  many  diseases  all 
that  is  known  has  been  tediously  worked  out  by  this  form  of  research. 
It  has  been  urged  that  the  end  attained  does  not  justify  the 
suffering  induced  in  the  animal  experimented  uj>on.  Such  an  objection 
need  not  be  answered  here,  since  those  who  hold  it  can  not  know  of 
the  advances  made  by  the  experimental  methods  of  study,  or  are  not 
in  that  condition  of  mental  receptivity  necessary  to  appreciate  scientific 
truths.  The  results  attained  by  the  investigation  of  disease  in  lower 
animals  have  probably  done  more  to  alleviate  suffering  in  them  than  in 
man. 

Comparative  pathology— ^the  study  and  comparison  of  morbid  proc- 
esses in  the  lower  animals  and  in  man — also  affords  ample  opportunity 
to  obtain  information  as  to  the  causes  of,  and  alterations  in,  disease. 

In  all  pathologic  study,  to  attain  the  best  results  the  statistical 
method  must  be  used  to  a  certain  extent.  The  collection  of  a  large 
number  of  cases,  with  a  careful  analysis  of  recorded  data,  can  but  yield 
valuable  conclusions.  The  constancy  of  associated  lesions — as,  for 
example,  the  association  of  certain  nervous  and  nutritive  phenomena 
with  removal  or  disease  of  the  thyroid  gland — often  indicates  a  path 
for  investigation  that  may  terminate  in  a  happy  solution  of  some 
obscure  problem. 

The  study  of  diseased  organs  or  tissues  postmortem  or  after  operative 
removal  from  the  body  need  hardly  be  mentioned  as  a  most  fruitful 
source  of  knowledge  concerning  morbid  processes. 

In  addition  to  the  above  methods,  it  can  not  be  an  error  thoroughly 
to  study  morbid  processes  during  life.  Therein  lies  the  strength  of 
the  science.  The  symptoms  of  a  disease  are  but  expressions  of  the 
lesions — the  morbid  physiology*  induced  by  chemic,  mechanical,  or  struc- 
tural alterations.  From  symptoms  it  is  possible  in  many  cases  to  infer 
the  character  of  the  tissue  changes,  or,  by  studying  the  alterations  in 
the  normal  chemistry  and  structure,  the  symptoms  may  be  explained. 
He  is  far  at  sea  who  believes  that  the  study  of  pathology  begins  and 
ends  with  the  postmortem. 


CHAPTER  I. 
THE  ABNORMAL;   MALPOSITION;   MALFORMATION. 

General  pathology  comprehends  those  variations  in  structure  and 
function  that  may  attack  any  organ.  It  is  the  study  of  morbid  processes 
independent  of  their  location,  while  special  pathology  is  the  study  of 
diseases  of  organs  independent  of  the  same  disease  occurring  elsewhere 
than  in  the  organ  under  consideration. 

In  order  to  appreciate  the  abnormal  it  is  necessary  to  have  some 
definite  idea  of  the  normal.  Information  with  regard  to  health  is  ob- 
tained by  studying  individuals  or  organs  not  manifesting  disease  and 
considering  as  normal  that  condition  which  is  commonest.  Difficult v 
is  encountered  in  accurately  judging  the  limitations  within  which  modi- 
fication of  structure  and  function  may  be  regarded  as  physiologic.  In 
most  instances,  however,  the  morphologic  and  physiologic  boundaries 
of  the  normal  are  sufficiently  circumscribed  to  permit  a  readv  recogni- 
tion of  conditions  that  pass  beyond  their  domain.  Any  deviation  from 
the  normal  must  be  recognized  as  belonging  to  the  malpositions,  mal- 
formations, or  diseases. 

MALPOSITIONS. 

Malposition  is  misplacement  of  an  organ  from  that  position  in  which 
it  is  most  commonly  found,  or  any  alteration  of  its  relation  to  other 
organs;  it  is  a  mal-posed  structure.  The  heart  may  be  rotated  on 
its  axis  and  not  occupy  the  normal  relation  to  the  surrounding  tissue, 
and  still  the  heart  may  be  in  place;  so  that  malposition  implies  either 
that  the  organ  is  not  in  place,  or  that,  being  in  place,  its  parts  do  not 
bear  their  normal  relation  to  adjacent  structures  themselves  normallv 
located. 

Congenital  malposition  may  consist  in  the  perpetuation  of  fetal 
characters,  and  not  infrequently  is  associated  with  malformation;  thus, 
failure  in  closure  of  the  body  cleft  anteriorly,  particularly  at  the  um- 
bilicus, may  permit  a  viscus  wholly  or  in  part  to  lie  outside  the  abdom- 
inal cavity ;  fenestra  in  the  diaphragm  may  allow  the  heart  to  descend 
into  the  abdomen  or  one  or  more  abdominal  organs  to  rise  into  the 
thorax  (congenital  diaphragmatic  hernia).  Organs  that  develop  in  one 
position  and  later  normally  acquire  another  may,  for  some  reason,  fail 
to  make  the  requisite  migration  and  persist  through  adult  life  in  a  posi- 
tion more  or  less  normal  in  the  embryo;  a  kidney  may  fiom  this  cause 
lie  near  the  median  line  or  the  testicle  remain  in  the  abdomen.  An  in- 
teresting form  of  congenital  malposition  is  that  represented  by  ectopia  of 
parts  of  organs,  although  the  term  is  also  used  for  entire  organs  occupying 
abnormal    positions.      Some  organs  show   the  most    extraordinarv  ten- 

58 


THE    abnormal;    malposition;     MALIdkMATION.  5Q 

dencv  to  partial  or  even  complete  ectopia;  thus  adrenal  tissue  may  be 
found  in  the  hver,  spleen,  neighborhood  of  the  ovary  or  testicle,  and 
IS  not  infrequently  present  in  the  kidney,  usually  the  cortex.  Aberrant 
pancreatic  lobules  occur  in  the  stomach,  duodenum,  jejunum,  and 
less  frecjuentlv  in  the  ileum;  gastric  glands  may  be  present  in  the  duo- 
denum or  in  the  esophagus;  fragments  of  thyroid  may  be  distributed 
along  the  course  of  the  thyroglossal  duct,  at  the  base  of  the  tongue, 
or  within  the  thoracic  cavity.  The  cause  of  these  various  forms  of 
ectopia  is  more  or  less  obscure;  the  usual  explanation,  that  they  de- 
pend upon  incarceration  of  growing  cells  in  abnormal  localities,  is  little 
more  than  a  restatement  of  the  primary  facts.  It  should  be  remem- 
bered that  such  ectopic  tissues  are  particularly  prone  to  manifest  tumor 
formation;  misplaced  testes  not  infrequently  become  sarcomatous  or 
carcinomatous;  lingual,  tracheal,  and  mediastinal  goiters  develop  from 
ectopic  thyroid  tissue,  and  the  relatively  frequent  tumor  called  a  hyjjer- 
nephroma"  is  the  result  of  neoplastic  activity  in  ectopic  adrenal  tissue. 

Congenital  malpositions  may  correct  themselves  or  be  corrected  by 
the  surgeon,  although  their  tendency  is  to  persist;  an  umbilical  or  in- 
guinal hernia  of  congenital  origin  may  be  replaced,  an  abdominal  testis 
mav.  bv  operative  procedure,  be  brought  to  its  normal  position;  a 
mesial  kidney  or  a  right-sided  heart  of  congenital  origin  will  probably 
never  occupv  the  position  of  the  normally  posed  organ. 

Acquired  malposition  may  result  from  congenital  defects,  disease, 
trauma,  etc.  Imperfect  closure  of  the  abdominal  parietes  at  the  um- 
bilicus, inguinal  or  femoral  outlets,  permits  the  occurrence  of  hernia 
at  these  points;  when  the  muscle  of  one-half  of  the  diaphragm  fails 
to  develop,  the  absence  of  contractile  power,  the  elasticity  of  the  lung, 
and  the  higher  abdominal  pressure  lead  to  eventration,  the  diaphrag- 
matic arch  of  that  side  rising  almost  to  the  apex  of  the  thorax,  permit- 
ting abdominal  organs  to  lie  within  the  chest  cage  but  not  in  the 
thoracic  cavity. 

Disease  may  in  a  number  of  ways  cause  malposition;  enlarged  or- 
gans mav  bv  their  increased  bulk  or  weight  drag  from  normal  attach- 
ments; this' is  especially  true  of  the  spleen,  kidney,  and  stomach,  and 
to  a  lesser  degree  of  the  pancreas,  transverse  colon,  and  gall-bladder. 
Disease  mav  also  alter  the  lines  of  pressure  and  displace  organs  not 
themselves  diseased.  The  heart  is  pushed  to  the  left  and  the  liver 
displaced  downward  by  gas  or  fluid  accumulations  in  the  right  pleura 
or  massive  solid  or  cystic  growths  involving  that  structure  or  the  lung. 
Acquired  malposition  may  result  from  loss  of  normal  support  by  reten- 
tive structures.  Wasting  of  the  abdominal  wall  favors  prolapse  of  the 
contained  viscera  (visceroptosis).  The  alteration  in  pressure  throws 
unusual  stress  upon  the  structures  normally  retaining  liver,  spleen,  and 
kidnevs  in  place,  as  a  result  of  which  change  these  organs  are  prone  to 
prolapse.  Loss  of  support  in  the  pelvic  floor  permits  of  uterine  displace- 
ments. Organs  mav  be  pulled  out  of  place  by  the  contraction  of  fibrous 
tissue.  In  chronic  interstitial  pneumonia  when  the  involved  lung  is 
firmlv  attached  to  the  chest  wall  contraction  of  the  newly  formed  hbrous 
tissue  tends  to  pull  the  heart  and  other  mediastinal  tissues  toward  the 
affected  side.  Inflammatory  conditions  may  perpetuate  inalpositions 
due  to  other  causes;  adhesions  may  render  reducible  hernias  irreduc- 
ible or  mav  eventuallv  bind  in  its  new  position  an  organ  but  tempo- 


6o  GENERAL    PATHOLOGY. 

rarily  displaced.  One  organ  wandering  from  its  normal  position  mav 
lead  to  displacement  of  another;  the  prolapsed  spleen  may  carry  with 
it  the  tail  of  the  pancreas;  the  transverse  colon  displaced  downward 
may  drag  upon  the  stomach  and  the  dilated  or  prolapsed  stomach  may 
in  turn  displace  the  colon. 

Trauma  may  in  a  number  of  ways  give  rise  to  malposition;  falls 
with  sudden  arrest,  or  blows  in  the  renal  region  may  loosen  normal 
attachments  and  be  followed  by  displacement  of  the  kidney.  Wounds 
m  the  abdominal  wall  may  cause  hernia  primarily,  or  secondarily  by 
imperfect  healing  and  relaxation  of  the  cicatrix.  Malpositions  due  to 
fractures  of  bone  and  misplacement  of  fragments,  or  dislocation  of  ar- 
ticular surfaces — constituting  both  a  malposition  and  an  abnormal 
formation — are  usually  referred  to  as  deformities,  although  to  the  lav- 
man  malposition,  malformation,  and  deformity  are  essentiallv  the  same. 

It  will  be  recognized  from  the  foregoing  that  malposition,  of  itself 
does  not  constitute  disease.  Misplaced  organs  may  be  functionally 
normal;  removed  from  the  body,  a  right-sided  heart  may  differ  in  no 
respect  from  a  normally  placed  organ.  As  already  intimated,  ectopic 
tissues  are  prone  to  disease,  and  frequently  manifest  more  or  less  per- 
version of  function;  it  is  usually  maintained  that  abdominal  testes 
produce  no  spermatozoa.  In  most  other  organs,  however,  function  is 
manifestly  adequate.  Malposition  not  infrequently  subjects  the  affected 
tissue  to  influences  not  exerted  upon  the  same  organ  in  its  normal  posi- 
tion; the  floating  spleen,  kidney,  or  liver  is  more  liable  to  injury  than  a 
normally  placed  organ.  Abnormal  position  not  infrequently  subjects 
nerves,  vessels,  and  ducts  to  unusual  stress;  traction  on  the  splenic 
pedicle  obstructs  the  vein  and  favors  congestion,  torsion  of  the  pedicle 
may  arrest  the  circulation.  The  ureter  of  a  floating  kidney  is  not 
infrequently  compressed,  angulated.  or  kinked,  therebv  impeding  the 
outflow  of  urine. 

MALFORMATIONS.  1 

Malformation  is  a  deviation  in  structure  and  development  from 
that  most  commonly  found.  A  malformed  structure  is  not  neces- 
sarily diseased, — although  it  may  have  resulted  from  disease  and  mav 
manifest  a  tendency  to  various  pathologic  processes  which  properly 
may  be  called  diseases.  Acquired  malformation  is  commonly  called  de- 
formity, although  the  liver  distorted  by  the  corset  is  usually  termed 
a  malformed  organ.  In  some  ways  maldevelopment  is  preferable  to 
malformation;  the  former  term  is  usually  applied  to  abnormal  condi- 
tions depending  upon  developmental  errors,  and  as  most  malformations 
properly  so  called  have  this  origin,  the  two  terms  tend  to  become  essen- 
tially synonymous. 

Teratogenesi's. — While  the  causes  of  malformation  may,  in  certain 
instances,  be  evident,  a  large  percentage  of  cases  are  inexplicable  by 
any  facts  at  present  in  our  possession.  It  must  be  apparent  that  any 
essential  abnormality  in  germ  or  sperm  cell,  or  both,  necessarily  tends 
to  abnormality  in  the  evolved  product  of  their  union.  Abnormal  in- 
fluences brought  to  bear  upon  the  impregnated  ovum  must  necessarily 

'Consult  Ballantyne,  "Manual  of  Antenatal  Pathology  and  Hygiene,"  "The 
Enibrj'o,"  1Q05. 


Till-;     AHNOKMAL,     M  ALroSlTK)N  ;     M  AI.  KOkM  ATlON .  '    : 

inodif)-  Its  growth.  It  is  therefore  apparent  that  certain  causi 
be  regarded  as  iiitrinsiL — having  their  origin  in  the  cells  from  which 
the  new  being  springs;  other,  causes  are  extrinsic,  depending  upon  in- 
tiuences  acting  upon  what  might  be  called  a  normally  disposed  develop- 
mental process.  An  important  member  of  the  intrinsic  causes  is  in- 
heritance; web-tingers  (syndactylism),  short,  stunted  fingers  or  toes 
(perodactylism),  harelip,  and  minor  abnormalities  arc  frecjuently  trans- 
mitted by  one  or  the  other  parent.  A  mother  may  bear  normal  chil- 
dren by  one  husband  while  by  another  the  offspring  may  show  malforma- 
tions transmitted  by  the  father.  When  a  malformation  is  traceable  to 
a  remote  rather  than  an  immediate  ancestor,  the  condition  is  called 
atovisDi,  or  reversional  heredity.  Closely  allied  to  the  transmi.ssion  of 
gross  morphologic  defects  must  be  classed  the  undemonstrable  cellular 
or  cytochemic  peculiarities  of  tissue  which  create  tendencies  to  dis- 
ease or  abnormal  susceptibilities,  to  which  reference  will  be  made  later. 

In  the  chick  it  has  1)een  demonstrated  that  such  external  influences 
as  temperature  change,  shellacing  the  egg,  frequent  shaking,  and  ab- 
normal posture  may  determine  malformation  in  the  ofTsjjring.  The 
human  embryo  in  ectopic  pregnancies  is  not  infretjuently  malformed. 
Abnormal  pressure  upon  and  abnormal  position  of  the  extremities  may 
modify  the  shape  of  the  bones  and  soft  parts.  Insufirtcient  amniotic 
fluid  especially  subjects  the  fetus  to  external  influences.  Adhesions 
between  the  embryo  and  the  amnion  and  abnormal  pressure  exerted 
by  the  membrane  may  also  be  causes.  Pressure  exerted  by  the  hand 
and  chin  on  the  thorax  may  interfere  with  development  of  the  sternum. 
The  funis  wrapped  around  an  extremity  may  by  pressure  cause  ampu- 
tation. It  has  been  alleged  that  increased  abdominal  or  uterine  pres- 
sure may  produce  malformations;  Ballantyne  does  not  hold  this  view, 
nor  does  he  look  with  favor  upon  the  often  expressed  opinion  that  mal- 
formation of  one  twin  may  be  due  to  pressure  exerted  by  the  other. 
These  and  similar  influences  are  called  the  cxtri)isic  causes  of  malforma- 
tion. The  earlier  these  influences  become  operative,  as  a  rule,  the  more 
marked  the  resulting  malformation. 

Nosologic  or  Pathologic  Theory. — Disease  of  the  fetus  may  g^ive 
rise  to  important  developmental  <iefects.  Obliterative  changes  in  the 
fetal  vessels  may  arrest  or  modify  the  development  of  the  affected 
tissues:  thus  occlusion  of  the  renal  artery  may  prevent  or  arrest  the 
evolution  of  the  kidney,  and  endocardial  lesions  causing  stenosis 
of  the  jmlmonary  artery  may  indirectly  prevent  perfect  closure  of  the 
v'entricular  septum.  Not  only  may  the  fetus  be  influenced  by  its  own 
diseases,  but  morbid  processes  (for  example,  infections)  in  the  mother 
may  exert  a  deleterious  action  on  fetal  growth. 

The  Embryologic  Theory. — It  is  recognized  that  in  many  malfor- 
mations there  is  little  more  than  perpetuation  of  normal  fetal  condi- 
tions; fissures  in  the  median  line,  whether  complete  or  incomplete, 
anterior  or  posterior,  are  more  or  less  ];erfect  perpetuations  of  develop- 
mental features.  While  recognizing  these  facts,  difficulty  still  remains 
in  explaining  why  the  normal  develojjmental  process  was  not  completed. 
The  abnormality  may  have  been  influenced  by  heredity,  the  fusion  ot 
abnormal  ova  and  sperm  cells,  abnormal  pressure,  amniotic  a-ll-.c-r'i  s. 
intrauterine  injury,  or  other  causes. 

Xo  satisfactorv  classification  of  malformations  can  readil 


62 


GEXERAL  PATHOLOGY. 


Minor  abnormalities  are  usually  called  congenital  malformations;  gross 
and  conspicuously  altered  individuals  are  termed  monsters.  When  but 
one  individual  is  affected,  it  is  called  a  single  malformation  or  a  single 
monster — monosomatous  terata  ;  the  terms  double  malformation  and 
double  monster  are  applied  when  two  or  more  fetuses  are  involved — 
polysomatous  terata.  Malformations  following  a  uniform  tvpe  are 
called  typical,  while  those  assuming  irregular  forms  are  called  atvpical; 
the  latter  do  not  yield  to  any  ideal  systematic  classification. 
Ziegler  recognizes  five  groups  of  single  malformations: 
(i)  Developmental  arrest  (monstra  per  defectum),  which  would  in- 
clude agenesis  or  aplasia — absence  of  an  organ  or  part — and  hypoplasia 

— imperfectly  developed  organ  or 
part.  With  this  group  would  also 
be  included  fissures  and  clefts  in 
the  median  line,  both  anterior  and 
posterior,  due  to  the  imperfect 
development,  faulty  or  non-union 
of  extensions  that  normally  meet 
in  the  median  line.  Cranial  defects 
belonging  to  this  class  I  have 
described  under  malformations  of 
the  central  nervous  system,  and 
facial  abnormalities  involving  the 
upper  respiratory  and  alimentary 
tracts  with  those  systems.  Other 
fissures  in  the  median  line  ante- 
riorly may  aft'ect  the  thorax 
(thoracoschisis)  or  the  abdomen 
(fissura  abdominalis  or  gastros- 
chisisj  or  both  (thoracogastros- 
chisis).  Such  malformations  mav 
be  associated  with  the  eventration 
of  one  or  more  organs  normally  en- 
closed within  the  cavities  affected. 
In  lesser  degrees  (fissura  stemi, 
fissura  abdominalis  incompleta ) 
the  cavities  are  enclosed  although 
the  walls  in  the  median  line  are 
more  or  less  weakened.  Affecting 
the  urinary  organs,  imperfect 
union  in  the  median  line  may 
give  rise  to  fissure  or  exstrophy 
of  the  urinary  bladder,  and,  when  projected  downward,  genital  fissure 
and  epispadias. 

(2)  When  the  growth  exceeds  the  normal  (monstra  per  excessum) 
the  affected  structures  are  increased  in  size  or  number,  or  both.  AVith 
this  group  would  be  included  partial  giant  growth,  general  giant  growth, 
and  accessory  and  supernumerarv  structures. 

(3)  Congenital  malposition  of  organs  (monstra  per  fabricam  alienam) 
is  represented  by  a  situs  transversus  (see  malpositions  of  heart,  stomach, 
liver,   spleen,   etc.). 

(4)  Persistent    fetal    structures    that    normally    disappear,    as,    for 


Fig.  4g. — Pygop.^gus. — (Debierre,  Simes'  translation.) 


THE   abnormal;   malposition;   MALI-ORMATION.  6,5 

example,  the  ihyro^lossul  duct,  the  jjersistence  of  which  may  cause 
cvsts  (see  inalformations  of  the  thyroid  j^dand).  or  the  omphalomesen- 
teric duct  (see  malformations  of  the  intestines). 

(5)  This  group  includes  true  anil  false  hermajjhroditism.  True 
hermaidirotlites  are  bisexual,  false  hermaphrodites  unisexual.  In 
hermaphrodismus  verus  testis  and  ovary  are  present.  In  pseudo- 
hermaphrodismus  various  combinations  of  the  male  and  female  char- 
acteristics ma)-  be  present,  the  true  sex  dejiending  ujjon  which  sexual 
glands  are  found  in  the  indi\-idual. 

The  double  monsters  (monstra  per  duplica),  or,  according  to  Ballan- 
tvne's  classification,  polysomatous  terata,  are  instances  in  which  two 
or  more  individuals  are  involved.  This  group  includes  monochorionic 
or  homologous  twins,  and  also  triplets,  cjuadruplets,  quintuplets,  all 
of  which  in  man,  according  to  Ballantyne,  should  be  classed  with  the 
terata.  When  the  individuals  communicate  with  each  other  by  the 
umbilical  vessels  in  or  near  tlje  single  i)lacenta,  they  are  said  to  be  allan- 
toido-angiopagous  twins;  usually  one  is  deformed.  When  the  twins 
are  so  joined  that  some  parts  are  structurally  continuous,  they  are 
called  duplicated  monsters  or  double  terata,  which  may  be  symmetric, 
— that  is,  both  approximately  equally  developed, — or  asymmetric,  in 
which  case  the  rudimentary  or  imperfectly  developed  individual  is 
said  to  be  a  parasite,  or  parasitic  upon  the  other.  When  the  individuals 
are  joined  together  posteriorly,  the  anterior  parts  are  said  to  l)e  dupli- 
cated (duplicatus  anterior).  In  the  pygopagus  the  coccygeal  or  sacral 
areas  are  fused.  In  the  ischiopagus  the  pelves  are  fused  end  to  end, 
the  sacra  being  apposed.  In  the  dicephalus  the  trunks  are  fused,  the 
heads  alone  or  the  heads  and  necks  more  or  less  clearly  separated.  When 
the  heads  alone  are  fused  (craniopagus)  the  fetuses  may  be  joined  end 
to  en<l  I  craniopagus  parietalisi.  the  anterior  parts  may  be  merged 
(craniopagus  frontalis  1,  or  the  junction  may  be  in  the  neighborhood 
of  the  inion  (craniopagus  occipitalis).  When  the  anterior  parts  of  the 
bodv  are  more  or  less  perfectly  fused,  the  condition  is  called  duplicitas 
posterior.  With  more  or  less  perfect  separation  of  the  trunks  and 
fusion  of  the  heads  the  syncephalus  results.  In  the  dipygus  only  the 
lower  half  of  the  trunk  and  extremities  are  duplicated.  Lateral  fusion 
(duplicitas  parallela")  is  rare.  Among  the  commoner  forms  of  double 
monster  are  tlic  xyphopagus,  in  which  union  occurs  at  the  xyphoid; 
a  more  extensive  union  in  the  breast-plate  is  called  a  sternopagus  ;  both 
these  forms  are  included  in  the  group  thoracopagus. 


CHAPTER  II. 
DISEASE. 

The  fact  that  the  normal  for  any  given  function  is  bounded  by 
relatively  widely  separated  extremes  renders  it  difficult  to  formulate  a 
definition  for  disease  that  will  at  all  times  fall  within  the  scope  of  morbid 
manifestations.  To  say  that  disease  is  any  tissue  alteration,  chemical 
or  structural,  altering  the  function  of  a  tissue  or  an  organ,  such  limita- 
tions being  beyond  the  extremes  of  the  normal,  rather  obscures  than 
clarifies  our  idea  of  the  condition.  Chantemesse  and  Podwyssotsk}' 
define  disease  as  the  sum  of  the  actions  and  reactions  provoked  in  the 
function,  structure,  and  harmony  of  the  organism  by  a  morbid  cause. 
The  changes  produced  by  disease  are  its  lesions ;  the  alterations  in  struc- 
ture, its  morbid  anatomy;  the  symptoms,  its  morbid  physiology;  per- 
manent tissue  alterations  are  its  results.  It  has  been  the  custom  to 
speak  of  organic  disease,  implying  thereby  disease  of  structure  or  struc- 
tural alteration,  evident  to  the  unaided  eye  (macroscopic  lesion)  or 
demonstrable  with  the  microscope  (microscopic  lesion).  Of  the  chem- 
ical alterations  in  tissue  we  know  much  less;  it  is  evident,  however, 
that  structural  changes  have  a  chemical  basis  and  are  associated  with 
an  abnormal  chemistry  in  the  tissues  involved.  The  fact  is  shown  by 
the  increased  collagen  of  fibroid  organs,  the  abnormal  oil  content  in 
fatt}''  infiltration  and  fatty  degeneration,  the  apparently  newly  formed 
substance  in  lardaceous  disease,  and  the  manufacture  and  deposit  of 
abnormal  pigments  in  certain  types  of  the  pigmentary  infiltrations ; 
with  the  more  subtle  chemistry  of  many  abnormal  processes  we  remain 
indifferently  acquainted. 

In  most  diseases  an  anatomical  basis — more  or  less  constant  altera- 
tion in  particular  tissues — can,  by  the  means  at  present  at  our  disposal, 
be  recognized.  There  is,  however,  a  relatively  large  list  of  morbid 
manifestations  possessing  no  demonstrable  tissue  alteration.  These 
are  called  functional  diseases,  and  include  such  clinical  phenomena  as 
palpitation  of  the  heart,  certain  types  of  vertigo,  hysteria,  neurasthenia, 
and  a  number  of  the  insanities.  Improved  technic  and  more  extended 
study  are  constantly  narrowing  the  realm  of  functional  disease,  and 
it  is  generally  recognized  that  the  term  is  a  cloak  for  our  ignorance 
but  expressing  the  limitations  of  our  knowledge.  The  most  reasonable 
explanation  of  these  obscure  diseases  is  the  hypothesis  that  they  depend 
upon  chemical  alterations  in  the  affected  tissues  or  are  responses  to 
the  influence  of  unidentified  poisons  acting  upon  cells  and  inducing  ab- 
normal manifestations  without  at  the  same  time  giving  rise  to  recogniz- 
able  structural  alterations. 

The  limitations  of  our  knowledge  are  such  as  to  render  accurate 
nosology  (the  scientific  classification  of  disease)  more  or  less  imperfect; 
a  classification  based  upon  cause  at  once  encounters  numerous  diseases 
the  causes  of  which  are  unknown;    if  we  turn  to  structural  change,  the 

64 


DISEASE.  f)5 

fact  confronts  us  that,  in  sonic  instances.  aj)i»arcntly  identical  lesions 
are  produced  by  different  causes.  Symptomatology  offers  us  nothinjj 
better,  and  hence  at  present  the  nosologist  is  driven  to  the  acceptation 
of  a  veritable  medley  in  which  the  strains  of  all  possible  bases  of  classi- 
fication may  be  recognized. 

With  regard  to  the  duration  of  disease  the  terms  acute  and  chronic 
are  usually  applied.  Acute  diseases  are  manifested  by  suddenness  of 
onset,  relatively  short  duration,  possess  fairly  constant  characters, 
are  not  infrequently  self-liniitcd,  and  usually  arc  marked  by  a  frank 
symptomatolog}-.  JFulminating,  foudroyant,  or  hyperacute  diseases 
are  characterizLMl  by  suddenness  and  intense  severity. 

Chronic  diseases  begin  insidiously,  frequently  imperceptibly,  al- 
though occasionally  they  are  the  perpetuation  of  acute  attacks.  They 
are  further  characterized  by  a  rather  indefinite  duration,  irregular  or 
varying  svmptoms,  which  not  infrequently  intermit  or  remit;  the  lesions 
mav  or  mav  not  be  accompanied  by  remission  or  intermission ;  commonly 
the  latter  are  uninterrupted,  although  the  rapidity  of  advance  often 
varies. 

Diseases  due  to  parasites  are  called  parasitic  diseases  ;  ordinarily 
the  use  of  the  term  is  restricted  to  morbid  processes  due  to  animal 
]^arasites.  Diseases  due  to  lower  forms  of  vegetable  life  arc  called 
bacterial,  microbic,  or  germ  diseases;  an  infection  evidently  due  to  a  living 
contagium  and  without  which  the  morbid  process  cannot  occur  is  called 
a  specific  disease.  Diseases  readily  transferred  from  man  to  man.  or 
from  animal  to  man.  are  called  communicable  ;  those  of  the  communi- 
cable diseases  transmitted  by  contact,  mediate  or  immediate,  are  termed 
contagious.  Diseases  due  to  the  entrance  and  proliferation  of  a  vege- 
tal)le  organism  in  the  tissues  of  the  body  are  also  called  infections  or 
infectious  diseases.  .Morl)id  ]irocesses  for  which  we  can  discern  no  ade- 
(luate  cause  are  called  idiopathic  ;  rather  than  say  idiopathic  or  of 
"self-origin"  it  would  be  better  to  use  cryptogenic,  meaning  of  hidden 
or  obscure  origin. 

A  disease  constantly  present  in  a  given  area  is  said  to  be  endemic ; 
when  occurring  only  occasionally,  sporadic.  When  a  large  number 
of  cases  occur  in  a  single  locality,  in  a  brief  period,  the  disease  is  epi- 
demic ;  when  an  epidemic  is  distributed  over  a  larger  area  a 
hemisphere. — it  is  called  a  pandemic. 

Traumatic  diseases  are  due  to  injury.  When  the  cause  enters 
bv  the  alimentarv  tract,  the  disease  is  said  to  be  of  ingestive  origin. 

It  is  often  convenient  to  divide  diseases  into  local  and  general,  the 
former  restricted  to  some  particular  organ  or  area  and  the  latter  showing 
a  much  wider  distribution.  Systematic  writers,  for  convenience  in  des- 
cription, not  infrequently  classify  diseases  on  an  anatomical  or  regional 
basis;  thus  surgeons  write  of  surgery  of  the  head,  the  internist  of  dis- 
eases of  the  pulmonarv  svstem.  the  gynecologist  on  affections  of^fbe 
reproductive  organs,  and  neurologists  on  diseases  of  the  nervpus  S^Stem. 

Complications  are  morbid  conditions  not  usually  constitutmg  a 
part  of  the  disease  with  which  they  occur  but  traceable  to  its  manites- 
tations;  thus,  perforation  of  the  intestine  is  a  complication  of  typhoid 
fever  resulting  from  extension  of  the  necrotic  process  in  the  typhoid 
ulcer  through  the  intestinal  wall.  They  differ  from  intercurrent  dis- 
eases, which  attack  a  patient  alreadr-  ''^'^  ^w  tim  r,f  <,,mr  .,t)i.r  att.-,  tmn. 


66  GENERAL    PATHOLOGY, 

Sequelae  are  morbid  processes  which  ordinarily  do  not  develop  until 
the  patients  have  almost  or  quite  recovered  from  the  diseases  to  which 
they  are  due.  The  distinction  between  sequel  and  complication  is  not 
always  clear;  a  nephritis  occurring  during  the  course  of  scarlet  fever 
is  a  complication;    appearing  later,  a  sequel. 

Pathogenesis  or  etiology  is  that  branch  of  pathology  dealing  with 
the  cause  of  disease.  Whatever  may  be  the  change  going  on  in  an 
organ  or  tissue,  it  must  be  recognized  that  there  is  some  underlying 
cause,  and  that  the  recognizable  manifestation  is  the  reaction  of  the 
structures  to  some  influence  the  exact  character  of  which  may  not  be 
known.  White  defines  a  cause  as  the  invariable,  unconditional  ante- 
cedent of  an  event,  which,  in  relation  to  the  cause,  is  called  the  effect. 
In  pathology  the  factor  or  factors  giving  rise  to  disease  constitute  its 
cause;  the  alterations  in  structure  and  function,  the  effect.  No  satis- 
factorv  classifications  of  causes  can  be  made,  although  general  sub- 
divisions are  recognized. 

Predisposing,  remote,  or  conditional  causes  are  those  favoring  the 
action  of  the  immediate,  unconditional,  or  exciting  causes.  Surgeons 
have  demonstrated  that  tissues  may  be  injured  without  the  occur- 
rence of  suppuration;  the  essential  cause  in  the  production  of  suppura- 
tion is  infection.  The  wound,  by  breaking  the  continuity  of  a  pro- 
tected surface,  injuring  the  tissues  and  introducing  bacteria,  indirectly 
causes  the  subsequent  inflammation  and  suppurative  processes.  Pre- 
disposing causes  are  not  specific,  exciting  causes  partake  more  of  this 
quality. 

There  are  certain  causes  that  are  inherent  to  the  individual ;  these 
are  called  internal,  intrinsic,  or  autogenous.  Among  this  group  should 
be  mentioned  age.  Some  diseases  are  largely  restricted  to  infancy; 
others  to  adolescence,  adult  Hfe,  or  old  age.  In  the  influence  exerted 
by  age  on  the  inception  of  disease  a  number  of  special  features  must 
be  recognized.  The  fact  that  in  infancy  and  in  youth  the  body  is  first 
exposed  to  certain  infectious  diseases  which,  if  once  acquired,  do  not 
recur,  renders  those  affections  common  during  that  period  in  life  not 
because  of  any  overwhelming  susceptibility  incident  to  the  age,  but 
rather  because  the  initial  exposure  happens  at  that  time.  There  can 
be  no  doubt,  however,  that  the  child  is  more  susceptible  than  the  adult 
to  certain  infections,  for  example,  scarlet  fever,  diphtheria,  and  infec- 
tions of  the  alimentary  canal.  The  susceptibility  of  young  bones  to 
infection  during  the  period  of  adolescence  is  probably  attributable  to 
the  vascularity  of  active  growth  and  the  frequency  with  which  injury 
occurs  at  that  time.  During  adult  life  the  individual  is  subjected  to 
the  dangers  of  the  heightened  activity  incident  to  the  period,  and  with 
old  age  come  lesions  of  the  vessels  and  failing  functional  activity  in  a 
number  of  tissues — especially  the  renal  and  cardiovascular  systems — 
which  in  time  bring  perils  of  their  own. 

Sex  influences  the  occurrence  of  disease  not  alone  because  of  ana- 
tomical and  physiologic  differences,  but  to  a  large  degree  on  account 
of  difference  in  habits.  The  fsct  that  the  mammary  gland  in  the 
female  is  functionally  active  through  a  large  period  of  a  woman's  life 
renders  it  particularly  prone  to  disease,  while  in  man  the  organ  is 
rarely  affected ;  the  short  urethra  of  the  female  renders  her  infrequently 
subject  to  vesical  calculus.     Man  falls  a  victim  to  diseases  favored  b\ 


i)isr:ASK.  67 


exposure,  tor  exanii)lc,  i>nL'unionia,  rheuiiiatisiii,  idul  sunstroke;  woman, 
as  a  result  of  her  immured  existence  and  consetiuent  deprivation  of 
fresh  air  and  sunUght.  is  especially  liable  to  anemia.  The  lax  soxmi' 
life  of  the  male  makes  him  the  frecjuent  subject  of  venereal  dis' 
and  his  less  restrained  appetite  brings  the  dangers  r)f  intemperain  . 
especially  alcoholism. 

Race. — The  negro  is  less  susceptible  to  malaria  than  the  Caucasian, 
but  is  a  great  sufferer  from  tuberculosis  in  all  its  forms.  Chorea  is 
rare  "r  uiiknown   in   the   Mongolian. 

Idiosyncrasy  is  an  unusual  susccjjtibility  to  the  injurious  action  of 
agencies  that  do  not  influence  other  individuals.  Some  ])crsons  are 
peculiarlv  susceptible  to  fish  or  mushrooms,  certain  odors,  or  particular 
medicaments,  especially  the  iodids,  opium,  or  quinin. 

Among  the  most  important  of  the  intrinsic  causes  of  disease  is 
heredity.  It  is  generally  agreed  that  there  is  no  essential  difference 
between  physiologic  and  pathologic  heredity.  Certain  diseases  seem  to 
be  essentially  the  results  of  heredity.  Important  among  these  can  be 
mentioned  the  hemorrhagic  diathesis  and  Freidreich's  ataxia,  both  of 
which  are  discussed  elsewhere.  Woods  Hutchinson  in  50,000  cases  of 
insanity  found  hereditary  influences  operative  in  22.6  per  cent.;  Mc- 
Gugan  think?  that  in  America  hereditary  tendencies  are  present  in  80 
to  90  per  cent,  of  the  cases.  It  is  not  possible  in  this  work  to  enter 
into  a  discussion  of  the  inheritance  of  acquired  characters,  but  there 
can  be  no  doubt  that  the  product  of  conception  is  materially  influenced 
bv  acquired  processes  affecting  the  parents.  The  frequency  with  which 
tuberculosis  attacks  those  of  a  certain  ancestry,  and  the  tendency  of 
the  offspring  of  syphilitic  parents  and  those  addicted  to  chronic  alco- 
holism to  certain  diseases,  must  generally  be  admitted.  It  seems  well 
established  that  the  mother  is  more  likely  to  transmit  than  the  father. 
Various  explanations  have  been  offered  for  the  high  mortality  of  cer- 
tain diseases  among  the  progeny  of  alcoholics  and  syphilitics.  It  seems 
highlv  probable  that  poisons  circulating  in  the  blood  of  a  i)arent  may 
influence  the  developing  sexual  cell,  rendering  the  offspring  more  sus- 
ceptible to  certain  diseases.  Noxious  influences  are  more  prone  to 
exert  their  deleterious  action  upon  highly  organized  tissues,  and  more 
especially  upon  structures  whose  highest  physiologic  action  has  been 
last  acquired  in  the  evolution  of  the  race.  If  this  view  be  correct,  it 
satisfactorily  explains  the  frequency  with  which  disease  of  the  nervous 
system  attacks  the  progeny  of  alcoholics,  syphilitics,  and  those  suffering 
with  chronic  lea'd-poisoning,  and  other  intoxications.' 

The  pre.sence  of  one  disease  may  predispose  to  another:  leukoplakia 
of  the  tongue  may  terminate  in  cancer;  diabetics  are  especially  suscep- 
tible to  certain  'infections,  and  j)atients  having  chronic  interstitial 
nephritis  are  more  liable  to  inflammation  of  the  serous  meml)ranes.  This 
increased  susceptibility  to  some  other  disease  is  probably  the  result 
of  the  deleterious  action  of  the  existing  process  on  the  normal  inhibit- 
ing influences  ot   the  body. 

The  external,  extrinsic,  or  exogenous  causes  of  disease  are  those 
factors  acting  upon  the  body  from  without.  Some  of  these  are  in  a 
way  special;   others  may  be  regarded  as  the  sum  total  of  man's  environ- 

'  For  bibliography  of    heredity  in   its  relation   to  pathology  see  Chan" 
and  PodwA-ssotskv.  "Les  Processes  G^nerau.x."    -  '    '   ■       ' 


68  GENERAL    PATHOLOGY. 

ment.  Certain  diseases  are  restricted  to  warm  countries,  because  in  such 
climates  only  are  conditions  suitable  for  their  propagation.  Those  dis- 
eases propagated  by  insects  cannot  occur  in  regions  the  climatic  condi- 
tions of  which  preclude  the  existence  of  suitable  insects.  This  is  espe- 
cially borne  out  by  our  knowledge  of  trypanosomiasis  and  malaria. 
The  influence  of  climate  on  disease  is  also  shown  by  the  occurrence 
of  seasonal  exacerbations  in  certain  affections  and  the  fact  that  some 
diseases  are  particularly  frequent  during  certain  months.  Cleemann 
found  that  of  621  cases  of  typhoid,  441  occurred  during  the  summer 
and  autumn.  Smallpox  is  most  active  between  December  and  Febru- 
ary; pneumonia  is  twice  as  frequent  in  the  winter  and  spring  as  in  the 
summer  and  autumn.  That  man  tends  to  adapt  himself  to  climatic 
influences  is  shown  by  the  heightened  susceptibility  to  tropical  dis- 
eases manifested  by  the  unacclimated. 

Certain  occupations  are  so  constantly  associated  with  definite  proc- 
esses that  the  latter  have  been  called  artisan's  diseases;  those  brought 
in  contact  with  lead  suffer  a  special  type  of  intoxication  called 
plumbism.  Laborers  in  dust-laden  atmospheres  acquire  pneumonoco- 
niosis;  the  pen  and  the  telegrapher's  key  induce  writer's  cramp  and 
telegrapher's  cramp  respectively. 

The  habits  of  the  individual  may  subject  him  to  special  dangers. 
Smoker's  cancer  follows  the  local  irritation  of  pipe  or  cigar  and  certain 
cardiac  and  nervous  phenomena  may  result  from  the  absorption  of 
poisons  derived  from  tobacco.  The  deleterious  effects  of  alcoholic  in- 
temperance are  well  known.  Mention  may  here  be  made  of  the  so-called 
mental  causes,  among  which  should  be  classed  prolonged  mental  effort, 
anxiety  and  worry,  and  the  depressing  influence  of  profound  emotion. 
The  prevalence  of  certain  diseases  of  the  nervous  system  is  directly 
attributable  to  the  great  strain  which  the  modern  life  throws  upon 
the  nervous  system. 

Starvation  and  Allied  Conditions. — The  inability  of  the  bod}^  to 
secure  the  materials  requisite  for  the  maintenance  of  function,  includ- 
ing growth  and  replacement  of  waste,  is  followed,  more  or  less  rapidly, 
by  well-marked  disturbances.  Deprivation  of  the  elements  requisite 
for  nutrition  may  be  dependent  upon  external  conditions,  or  may,  to 
a  certain  extent,  arise  from  perversion  of  normal  processes.  Thus, 
the  cutting-off  of  oxygen  may  be  dependent  upon  its  absence  or  scanti- 
ness in  the  surrounding  medium,  as  when  the  body  is  submerged  in 
water,  or  it  may  be  due  to  occlusion,  to  spasm,  or  to  the  presence  of  a 
foreign  body  in  the  air-passages;  or,  as  a  result  of  altered  absorbing 
power,  the  blood  may  not  be  able  to  take  up  the  gas  even  when  the 
latter  is  abundantly  supplied  in  the  vesicular  structure  of  the  lungs. 
In  carbon  monoxid  poisoning  the  gas  seems  to  combine  so  firmly  with 
the  oxygen-carrying  bodies  that  it  can  not  be  displaced,  and  no  mat- 
ter how  rich  in  oxygen  the  inspired  air  may  be,  it  is  not  absorbed  as 
in  health.  The  changes  induced  are  largely  dependent  upon  the  ex- 
tent to  which  the  supply  is  diminished,  the  duration  of  the  oxygen 
starvation,  and  the  facilities  afforded  for  the  excretion  of  materials  the 
accumulation  of  which  is  favored  by  the  absence  of  the  normal  respi- 
ratory interchange.  If  the  amount  of  oxygen  supplied  be  but  moder- 
ately diminished,  the  most  frequent  changes  occurring  in  the  fluids  and 
organs  of  the  body  are  degenerative  processes,  so  slowly  brought  about 


DISEASE.  69 

as  to  be  inconspicuous  until  in  an  advanced  stage.  The  more  marked 
or  more  rapid  lessening  of  the  supply  of  oxygen,  such  as  results  from 
pressure  of  exudates  or  tumors  without  the  laryn.x  or  swelling  within, 
gives  rise  to  the  condition  known  as  asjihyxia.  In  the  production  of 
the  phenomena  grouped  under  this  heading  the  accumulation  of  carbon 
dioxid  has  probably  more,  or  certainly  equally  as  much,  to  do,  as 
the  associated  diminution  in  the  quantity  of  oxygen  jiresent. 

Food  and  drink,  as  well  as  oxygen,  are  necessary  for  the  mainten- 
ance of  life,  and  a  marked  reduction  in  the  sup])ly  of  any  of  these  will 
be  associated  with  evident  changes  in  the  nutrition  of  the  organism. 
As  is  the  case  with  oxygen,  so  we  find  with  food:  the  intensity  of  the 
lesions  produced  depends  largely  upon  the  extent  and  rapidity  with 
which  the  food-supply  is  reduced.  Insufficient  nourishment  usuallv 
gives  rise  to  lessened  resistance  on  the  part  of  the  individual,  rendering 
him  more  susceptible  to  the  action  of  causes  that,  under  ordinary  cir- 
cumstances, would  produce  no  effect.  With  the  complete  withdrawal 
of  food  and  water  there  is  rapid  combustion  of  the  fats  of  the  bod  v. 
associated  with  the  destruction  of  the  proteids  and  the  rapid  loss  of 
water.  The  tissues  whose  functions  can  be  best  spared  sufTer  most; 
in  prolonged  starvation  Voit  found  that  the  weight  of  the  brain  and 
spinal  cord  diminished  three  per  cent,  while  the  fatty  tissues  of  the 
liody  lost  ninety-six  per  cent.  This  fact  is  supported  by  the  early  utili- 
zation of  the  fat,  by  the  progressive  wasting  of  the  skeletal  muscles, 
and  by  the  fact  that  the  heart,  kidneys,  and  nervous  system  are  the  last 
to  suffer  and  are  the  least  altered.  Parenchymatous  changes  are  ob- 
servable in  nearly  all  the  organs,  and  toward  the  last  these  changes  mav 
become  marked  in  organs  the  function  of  which  is  absolutely  necessarv 
for  the  maintenance  of  life.  In  addition  to  the  absence  of  food  and  the 
fact  that  the  body  must,  in  a  certain  way,  consume  its  own  tissue  to 
maintain  heat  and  to  supply  the  force  requisite  for  carrying  on  respira- 
tion, circulation,  etc.,  there  is  also  an  accumulation  within  the  body  of 
poisons  that  tend  to  induce  disintegration  of  the  tissue  elements. 

(Jrdinarily,  the  occurrence  of  starvation  is  dependent  upon  the  in- 
ability of  the  organism  to  obtain  food;  but  occasional  instances  occur 
in  which  as  a  result  of  degenerative  lesions  of  the  mucosa  of  the  alimen- 
tary canal,  and  from  other  causes,  the  power  of  the  organism  to  digest 
or  to  assimilate  availal)lc  pabulum  is  lost,  and  death  occurs  as  a  result  of 
starvation,  although  abundant  food  is  supplied.  vStarvation  may  result 
from  more  or  less  marked  occlusion  of  the  esophagus  by  stricture, 
tumors,  etc. ;  under  such  conditions,  l)efore  the  advent  of  modern  sur- 
gery', cases  of  starvation  were  occasionally  observed.  As  Viefore  indi- 
cated, starvation  may  be  dependent  upon  lesions  of  the  secondary'  as 
well  as  of  the  primary  assimilative  forces.  Thus,  in  certain  blood  dys- 
crasias  the  error  of  assimilation  seems  to  l)e  not  in  the  digestive  organs, 
properly  so  called,  but  in  the  power  of  the  system  to  utilize  the  material 
supplied. 

Food  supplied  to  the  body  or  to  an  organ  is  utilized  for  replacing 
waste,  for  maintaining  growth,  when  this  is  necessary,  and  for  the 
continuance  of  other  functions.  If  an  organ  be  called  upon  to  accom- 
plish more  work  than  is  possible  with  the  food  available,  it  is  overworked, 
and  the  results  of  this  overwork  become  at  once  manifest.  These 
are  not  unlike  the  alterations  dependent  upon  scanty  or  inadequate  food; 


yo  GENERAL    PATHOLOGY. 

in  fact,  the  two  conditions  are  essentially  similar.  An  organ  doing 
little  or  no  work  utilizes  but  little  pabulum;  on  the  other  hand,  a  greatly 
overworked  organ  may  demand  more  nutrition  than  may  be  available, 
or  the  very  fact  that  it  is  manifesting  excessive  functional  activity  may 
lessen  its  "power  to  assimilate  the  nourishment  supplied.  In  addition 
to  the  foregoing,  nourishment  of  an  organ  is  dependent  not  only  upon 
its  reception  of  the  required  amount  of  food,  but  also  upon  its  ability 
to  throw  off  the  products  of  its  own  activity.  An  organ  greatly  over- 
worked may  be  so  situated  as  to  permit  accumulation  in  its  interiox 
of  one  or  more  poisons  the  presence  of  which  exerts  a  deleterious  in- 
fluence upon  the  cellular  elements  of  its  own  tissue.  As  an  example 
of  this  form  of  exhaustion,  which  is  really  but  another  name 
for  starvation,  may  be-  mentioned  the  important  structural  lesions 
noted  by  Hodges  in  the  ganglion  cells  of  pigeons.  It  has  been  said 
that  tissues  are  not  nourished,  they  nourish  themselves;  for  the  proper 
execution  of  this  function  food  must  be  supplied,  the  cell  must  be  able 
to  utiHze  the  pabulum,  and  removal  of  effete  material  must  be  sufficient; 
failure  in  the  fulfilment  of  any  of  these  requirements  leads  to  structural 
lesions,  and  thereby  to  disease. 

The  thermal  causes  of  disease  may  be  grouped  under  several  headings : 
(i)  The  local  influences  of  very  high  and  of  very  low  temperatures 
as  applied  directly  to  cutaneous  or  mucous  surfaces;  (2)  the  influence 
of  elevated  temperatures  upon  the  heat-coordinating  apparatus  of 
the  individual;  (3)  the  influence  of  cold  on  the  structure  and  function 
of  tissue. 

Burns  and  Scalds.' — The  character  and  extent  of  the  local  changes 
induced  bv  exposing  tissues  to  elevated  temperatures  are  dependent 
upon  the  tissue,  the  length  of  exposure,  and  the  height  of  the  tempera- 
ture. The  more  deHcate  tissues  are  susceptible  to  slight  rises  of  tem- 
perature, while  the  palm  of  the  hand  and  the  sole  of  the  foot  may  be 
accustomed  to  withstand  temperatures  which  would  be  destructive  to 
tissues  richer  in  juices  and  cellular  elements.  Comparatively  low  tem- 
peratures— 50°  C.  to  55°  C. — may  be  followed  by  vesication  and  necro- 
sis; in  individuals  whose  resistance  is  depressed  by  hemorrhage,  exhaust- 
ing sickness,  or  similar  conditions,  even  lower  temperatures  may  be 
destructive  to  vitality.  When  the  temperature  is  comparatively  low, — 
41°  C.  to  52°  C, — the  length  of  time  of  the  exposure  determines,  to  a  large 
degree,  the  extent  of  the  injury.  Ordinarily,  the  local  appHcation  of 
temperatures  under  from  50°  C.  to  51°  C.  is  not  associated  with  any 
marked  structural  change.  When,  however,  temperatures  begin  to 
ascend  above  this  point,  cell  destruction  is  likely  to  occur,  associated 
with  the  formation  of  exudates  of  various  kinds  and  with  inflammatory 
processes  of  varying  degrees  of  intensity. 

W^ith  regard  to  the  local  application  of  cold,  the  changes  brought 
about,  when  the  reduction  of  temperature  is  sufficient,  very  closely 
resemble  those  produced  by  high  temperatures.  The  application  of 
liquefied  air  produces  such  extensive  necrosis  that  it  has  been  proposed 
to  utilize  the  agent  as  an  escharotic,  exactly  as  caustics  may  be  applied 
for  the  destruction  of  morbid  growths.     Rischpler-  finds  that  all  soft 

1  Bardeen,  "Jour,  of  Exp.  Med.,"  iSgj,  vol.  ii.  p.  501:  McCrae,  '■  Deut.  Zeit. 
f.  Chir.,"  1903.  vol.  Lx,  p.  469:  Vernly.  "  Rif.  Med.,"  June  17.  1903:  Locke. 
"  Boston  Med.  and  Surg.  Jour.,"  Oct.   30.  1902. 

-"  Ziegler  Beitrage."  1900,  vol.  xxviii. 


niSKASE.  71 

tissues,  with  possible  exception  ol  the  elastica.  are  influenced  by  freezing; 
vacuolization  and  granular  changes  are  most  conspicuous;  the  cells 
shrink  and  the  nuclei  manifest  distortion  with  marked  alterations  in 
the  chromatin  reaction.  If  the  temperature  has  been  low  or  the  ex- 
posure ])rolonged,  cell  death  results. 

Attemi)ts  have  been  made  to  classify  burns  according  to  their  in- 
tensitv  or  the  extent  of  the  destruction  induced;  such  classifications 
must,  of  necessity,  be  arbitrary,  as  all  degrees  and  stages  must  merge 
into  one  another,  there  being  no  sharp  lines  of  demarcation.  Thus, 
it  is  said  that  bums  of  the  first  degree  are  associated  with  slight 
hvperemia  and  followed  by  a  more  or  less  superficial  desquamation. 
Hums  of  the  seeoiui  degree  give  rise  to  the  formation  of  blebs,  with  lique- 
faction necrosis  and  exfoliation  of  a  certain  amount  of  destroyed  tissue, 
but  not  involving  all  the  layers  of  the  skin.  Bums  of  the  third  degree 
involve  the  entire  skin,  and  terminate  in  the  formation  of  eschars 
composed  largely  of  that  structure.  Hums  of  the  fourth  degree 
imply  a  still  more  extensive  destruction  of  the  tissues,  amounting  prac- 
tically to  carbonization. 

These  classifications  are  largely  concerned  with  the  local  influences 
of  the  heat,  and  do  not  take  into  consideration  the  systemic  phenomena. 
The  latter  are  dependent  more  upon  the  amount  of  surface  involved 
than  upon  the  degree  of  the  burn.  When  over  one-third  of  the  cutane- 
ous surface  is  seriously  impaired  by  the  burn,  the  injury  is  likely  to 
prove  fatal.  A  number  of  theories  have  been  advanced  to  explain 
this  well-known  fact.  When  death  follows  immediately  upon  the 
inception  of  injury,  probably  the  only  factor  with  which  w-e  have  to 
deal  is  shock.  When,  however,  death  occurs  some  time  later, — pre- 
ceded by  focal  hemorrhages  aiid  necroses  in  one  or  more  organs,  par- 
ticularly in  the  alimentary  canal  and  liver,  and  by  hematuria,  hemo- 
globinuria, and  other  evidences  of  violent  intoxication, — it  must  be 
evident  that  we  are  dealing  with  something  more  than  shock  pure 
and  simple.  Among  the  explanations  which  have  been  offered  the 
following  may  be  mentioned: 

(i)  Suppression  of  the  cutaneous  functions  of  the  area  involved: 
(2)  perturbed  or  altered  nervous  system,  the  perturbation  or  alteration 
being  dependent  upon  reflex  phenomena;  (3)  the  formation  of  toxic 
substances  in  the  blood;  (4)  the  destruction  of  blood  elements;  (5) 
the  absorption  of  ptomains  or  other  poisons  from  the  injured  area. 
As  experimental  evidence  can  be  adduced  to  show  that  poisons  are 
present  in  the  blood  under  such  circumstances,  it  may  be  reasonal»le 
to  presume  that  they  are  influential  in  bringing  about  the  fatal  ter- 
minations. Exactly  what  is  their  origin  or  their  character  must  remain 
for  the  present  an  open  question.  Bardeen  has  shown  that  degenera- 
tion and  areas  of  necrosis  involve  the  renal  and  hepatic  parenchyma 
and  that  the  lymphatic  tissues  throughout  the  body  become  edematous 
and  at  points  necrotic.  The  lesions  observed  are  strikingly  similar  to 
those  produced  by  the  poisons  of  such  infectious  diseases  as  diphtheria; 
he  concludes,  therefore,  that  death  is  the  direct  result  of  the  toxemia. 
McCrae  regards  the  changes  in  the  lymph-nodes  as  proliferative,  but 
of  toxic  origin.  Locke  has  shown  that  in  severe  l)urns  the  red  cells 
increase  from  1.000,000  to  2.000.000  per  cmm..  and  in  fatal  cases  from 
2.000.000  to  4.000.000.     Leukocytosis  from  40.000  to  50.000  promptly 


72  GENERAL    PATHOLOGY. 

occurs.  The  blood  is  dark  and  flows  sluggishly.  As  stated  by  Wilms, 
the  conspicuous  excess  in  erythrocytes  is  clearly  due  to  concentration 
resulting  from  the  loss  of  serum. 

As  a  result  of  exposure  to  considerable  elevation  in  the  temperature 
of  the  surrounding  medium,  the  heat-coordinating  power  of  the  body 
may  be  altered  in  a  quite  characteristic  manner,  giving  rise  to  the  well- 
recognized  condition  known  as  sunstroke — a  morbid  process  dealt  with 
elsewhere. 

The  local  application  of  cold  induces  changes  closel}"  resembling 
those  produced  bv  heat.  An  extremely  low  temperature  in  the  sur- 
rounding medium,  aside  from  the  local  changes,  brings  about  a  more 
or  less  gradual  reduction  in  the  activity  of  the  body  functions,  and 
eventually  causes  death.  Exposure  to  very  low  temperatures  is  slowly 
followed  by  reduction  of  the  temperature  of  the  body.  When  this 
reduction  exceeds  about  13°  C,  death  usually  results.  When  the 
temperature  of  the  body  is  reduced  to  26°  C,  or  possibly  a  degree  or 
so  lower,  recovery  is  possible;  after  apparent  recovery  the  temperature 
may  rise  above  the  normal,  and  death,  preceded  b}^  more  or  less  fever 
and  emaciation,  sometimes  occurs  even  at  this  late  period.  Fischl 
has  shown  that  if  the  temperature  of  rabbits  be  artificially  reduced 
by  exposing  them  to  cold,  the  susceptibility  of  the  animal  to  infections, 
and  particularly  the  pneumococcus,  is  notably  increased. 

The  x-ray  induces  well-marked  lesions  in  tissues  exposed  to  its 
action;  the  resulting  affection  may  be  acute  or  chronic.  The  former 
may  be  a  simple  dermatitis  or  associated  with  actual  necrosis  of  tissue. 
Codman  found  that  of  167  cases,  53  were  forms  of  dermatitis,  14  burns 
of  the  first  degree,  29  of  the  second  degree,  and  71  of  the  third.  Some 
individuals  manifest  a  marked  susceptibility  to  the  ray.  The  pro- 
longed or  repeated  action  of  the  ray  produces  a  definite  tissue  necrosis 
(burn),  the  affected  cells  dying,  fragmenting,  and  desquamating,  or, 
when  deeply  seated,  possibly  undergoing  absorption.  It  is  commonly 
alleged  that  most  of  the  influence  induced  by  the  :v-ray  is  trophic  in 
nature,  but,  while  admitting  a  possible  or  frequent  trophic  action,  the 
fact  that  excised  tissues  may  be  changed  by  the  ray  and  that  neoplastic 
structures  (particularly  superficial  cancer)  and  tuberculous  tissues, 
but  little  subject  to  trophic  influences,  are  profoundly  susceptible  to 
its  action,  all  speak  for  its  necrosing  qualities.  Some  of  the  effects 
produced  by  the  ray  may  be  due  to  endovascular  changes — prolifera- 
tion of  endothelium  and  consequent  narrowing  of  the  vessel  lumen — 
lessening  the  nutrition  of  the  involved  tissues. 

Trauma  as  a  cause  of  disease  can  be  little  more  than  mentioned 
at  this  point.  (See  articles  on  Inflammation  and  Repair.)  Its  re- 
lation to  morbid  processes  will  become  more  evident  as  we  proceed. 
As  a  result  of  trauma,  more  or  less  destruction  of  tissue  occurs,  asso- 
ciated with  laceration  and  fragmentation  of  adjacent  or  more  resistant 
cells,  which,  though  not  actually  destroyed  by  the  injury,  are  no  longer 
capable  of  resuming  active  functions,  and  eventually  die  and  disintegrate. 
During  the  absorption  and  removal  of  the  dead  tissue  certain  poisons 
are  formed  the  activity  of  which,  in  the  production  of  both  local  and 
systemic  symptoms  and  lesions,  can  not  be  overlooked.  Aside  from 
these  direct  results  of  wounds,  whether  the  latter  be  large  or  small, 
the  possible  introduction  of  irritants,  which  may  further  injure  the  tissue. 


DISEASE.  7;? 

must  not  be  overlooked.  The  irritants  introduced  by  wounds  may  be 
microscopic,  and  of  themselves  of  but  little  im]jortance:  for  example, 
the  pigment  introduced  in  tattooing.  As  a  result  of  the  acicular  charac- 
ter of  certain  introduced  bodies,  such  as  scales  of  steel,  more  extensive 
cellular  alteration  may  be  brought  about.  Again,  these  bodies  may  be 
poisons,  giving  rise  to  extensive  degeneration,  necrosis,  and  inflamma- 
tion, such  as  is  seen  in  and  around  the  matrices  of  the  nails,  or  in  the 
skin  as  a  result  of  injury  and  the  introduction  of  the  cyanid  salts  u.sed 
in  photography.  Aside  from  the  direct  destructive  influence  of  injuries 
and  the  incidental  introduction  of  inorganic  substances,  irritant  and 
otherwise,  the  introduction  of  infective  bodies — bacteria  of  all  kinds — 
may  be  mentioned  at  this  point,  although  they  will  be  more  specifi- 
callv  considered  in  connection  with  bacteria,  and  again  when  treating 
of  wounds,  repair,  etc.  The  possible  relation  of  tumor  formation  to 
trauma  will  be  considered  elsewhere.     (See  Tumors.) 

Alterations  in  Atmospheric  Pressure. — A  sudden  fall  of  atmospheric 
pressure,  such  as  is  observed  in  balloon  ascensions  and  in  mountain 
climbing,  mav  give  rise  to  palpitation  of  the  heart,  respiratory  em- 
barrassment, mucous  and  submucous  hemorrhage,  unconsciousness, 
and  even  death.'  More  or  less  prolonged  residence  in  a  rarefied  atmos- 
phere mav  cause  an  increase  in  the  number  of  red  blood-cells  in  the 
peripheral  circulation  and  notably  augment  the  amount  of  hemoglobin. 
Many  of  the  symptoms  have  been  attributed  to  lack  of  oxygen  or  to  the 
inabihty  of  the  blood  to  absorb  oxygen  in  its  more  rarefied  form,  and 
also  to  the  influence  of  rapid  evaporation  of  water  that  takes  place 
under  lessened  atmospheric  pressure. 

Laborers  in  caissons  and  divers  suft'er,  on  their  return  to  the  normal 
atmospheric  pressure,  from  a  series  of  phenomena  to  which  has  been 
given  the  name  caisson  disease.  The  incidence  of  the  disease,  rapidity 
with  which  it  occurs,  and  the  severity  depend  upon  the  condition  of 
the  individual,  the  ventilation  of  the  enclosed  chamber,  and  the  amount 
and  duration  of  the  compression.  Under  an  increased  pressure  amount- 
ing to  ten  kilo,  men  usually  can  w^ork  eight  to  ten  hours;  fifteen  kilo 
can  not.  with  safety,  be  withstood  over  three  hours;  when  the  pressure 
reaches  twenty  kilo  thirty  minutes  is  all  that  can  be  borne  with  safety. 
The  great  danger  is  rapid  decompression;  if  the  locking-out  be  suffi- 
cientlv  slow^  no  symptoms  appear.  Crile  and  Macleod  -  have  demon- 
strated that  the'  symptoms  and  lesions  are  due  to  the  presence 
of  gaseous  emboli  in  the  capillaries  w^hich  may  rupture  and  per- 
mit the  escape  of  gas  and  blood  into  the  surrounding  tissue.  The 
symptoms  come  on  shortly  after  decompression,  but  may  be  delayed 
a  number  of  hours.  In  fatal  cases  there  is  marked  congestion  of  the 
central  nervous  system  and  thoracic  viscera;  inflammation  of  the  lungs 
has  been  recorded.  Hemorrhages  in  the  spinal  cord  and  clear  vacuolated 
areas  are  also  found;  secondar\'  softening  and  degenerative  changes 
may  follow  severe  lesions. 

'  For  V)ibliographv  of  mountain  sickness  see  article  \>y  J  .  Clittoni  .Aiibuu. 
•  AUbutt's  System  of' Medicine."  vol.  ii.  p.  456- 

'"  Tour,  of  Hvgiene."  October.  1003,  p.  481;  see  also  Ficsslcr.  "  Deut.  Arch, 
f.  klin.'Med.."  1904.  Brl.  81,  H.  5  and  6:  Aldrich.  '•  Medical  Xews."  November  an, 
1904. p.  IC20.  See  also  Lie.  'Virchow  Archiv."  Bd  t-s  t,  r  i^  ..n  •Ch.in-cs  m  the 
Central  Nervous  System." 


74 


GENERAL    PATHOLOGY. 


Electric  discharges  as  causes  of  disease  and  death  have  assumed  con- 
siderable importance  since  the  wide-spread  introduction  of  electricity. 
The  burns  produced  by  electricity  manifest  nothing  peculiar  or  character- 
istic, with  the  possible  exception  of  vagaries  in  distribution.  As  a  rule, 
the  phenomena  induced  by  electric  discharges  are  most  marked  in  in- 
tensity at  the  time  of  their  occurrence,  and  rapidly  disappear;  only  in 
rare  instances  do  they  persist.  The  effects  of  electric  shock  are,  of 
course,  dependent  upon  the  intensity  and  duration.  After  Itglii- 
ning-stroke  the  clothing  is  frequently  found  torn,  and  sometimes 
distributed  in  fragments  some  distance  from  the  body.  The  foot 
covering,  probably  by  reason  of  its  immediate  contact  with  the 
earth,  and  possibly  as  a  result  of  changes  in  its  conductivity  and  of 

irregularity    of    moisture    in    its    in- 
terstices, commonlv  suffers  most. 

Aspinall,  ^  Jellinek.  -  Crile  and 
Macleod^  have  especially  studied  in- 
juries and  death  due  to  electricity. 
Jellinek  refers  to  an  instance  in  which 
95  volts,  under  extremely  advantage- 
ous conditions,  caused  death,  and 
another  in  which  recovery  followed 
a  shock  by  5500  volts.  It  is  gener- 
ally believed  that  alternating  cur- 
rents are  more  dangerous  than  direct, 
although  with  this  view  Aspinall  does 
not  agree.  According  to  this  ob- 
server, 600  volts  require  abnormally 
favorable  conditions  in  order  to  prove 
fatal.  Jellinek  is  of  the  opinion  that 
exposure  to  a  current  of  100  volts 
requires  precaution,  200  volts  may  be 
dangerous,  and  500  volts  can  prove 
fatal.  The  direction  of  the  current 
through  the  body  is  important ; 
Aspinall  believes  the  left  side  more 
vulnerable  than  the  right.  Some  in- 
dividuals are  much  more  susceptible 
than  others  and  the  same  individual  does  not  always  show  equal 
resistance.  Aspinall  holds  that  during  sleep  severe  shocks  are 
well  borne;  idiots  are  quite  tolerant  to  high  voltages.  At  post- 
mortem lesions  may  be  difficult  to  recognize,  and  occasionally  are 
microscopic  only;  the  brain  and  membranes  usually  show  hyperemia 
and  hemorrhages  which  may  be  macroscopic  or  microscopic  and  are 
usually  most  marked  in  the  gray  matter.  The  cerebrospinal  fluid  is 
increased  and  there  is  congestion  of  the  internal  organs,  especially  the 
lung,  liver,  and  kidney.  Jellinek  has  described  definite  changes  in  the 
ganglion  cells  of  the  brain  and  cord,  manifested  by  chromatolysis,  tigrol- 
ysis,  displacement  of  the  nuclei,  abnormal  cell  contour,  and  swelling 
of  the  axis-cylinders.     These  lesions  account  for  the  paralysis  and  ner- 

'  "  Lancet,"  March  S,  1902. 

^"Lancet,"  Feb.  7.  1903,  p.  357;     also  "  Virchow  Archiv,"  Bd.  170,  H.  i. 

^  "  Amer.  Jour,  of  the  Med.  Sciences,"  March,  1905,  p.  417. 


Fio.  50  ■ 


-Marks  Produced  by  Lightning. — 
(^Ziegler.) 


niSHASK. 


75 


vous  phenomena  that  sometimes  follow  H,t(htnin<,'  stroke  and  other 
electric  injuries.  Sj^tzka  in  the  study  of  a  criminal  killed  by  electricity 
noted  a  marked  postmortem  rise  in  tem])erature. 

Amonjj^  the  most  im])ortant  causes  of  morbid  processes  are  substances 
ordinarily  desij^natcd  poisons.  The  old  idea  of  a  poison  was  something 
introduced  from  without,  entering  the  body  by  way  of  the  alimentary 
canal,  respiratory  organs,  skin,  or  genito-urinary  system.  With  pre- 
formed poisons  of  the  foregoing  type  the  toxicologists  and  students  of 
legal  medicine  particularly  have  to  deal.  An  extended  knowledge  of 
])hysiologic  and  pathologic  chemistry,  and  a  more  intimate  ac(|uaintance 
with  morbid  processes,  have  led  to  the  recognition  of  an  entirely  different 
group  of  poisons  having  their  origin  within  the  body,  some  of  them  the 
product  of  tissue  cells.  The  resulting  enormous  extension  of  the  held 
covered  by  the  term  ])oison  has  led  to  great  confusion  and  more  or  less 
ineffectual  attempts  at  satisfactory  classihcation;  much  that  was  old 
had  to  be  set  aside  or  readapted  to  new  conditions,  and  the.  greatest 
difficulty  was  encountered  in  properly  bringing  together  and  classify- 
ing the  newly  acquired  data.  With  the  pre-formed  poisons,  entering 
from  without,  but  little  difficulty  arose.  These  were  called  exogenous 
or  extrinsic,  and  were  further  subdivided  according  to  their  origin,  jjor- 
tal  of  entry,  or  the  character  of  the  lesions  that  they  produced. 

From  their  source  they  may  be  recognized  as  of  aiiiiiial,  vegclahlc,  or 
mineral  origin;  with  the  hrst  of  these  would  be  grouped  the  venom  of 
serpents,  the  poisons  of  bees,  biting  insects,  cantharidin,  etc.  Belong- 
ing to  the  second  group  are  opium,  strychnin,  atropin,  and  other  well- 
known  remedies  derived  from  the  vegetable  kingdom.  The  poisons 
of  mineral  origin  include  arsenic,  copper,  phosphorus,  mercury,  lead, 
zinc,  etc. 

Most  of  the  poisons  belonging  to  these  groups  enter  Ijy  the  alimentary 
canal,  a  few  may  be  introduced  by  cutaneous  absorption;  some  enter 
with  the  inspired  air.  Entrance  by  way  of  the  genito-urinarv  system 
is  rare. 

According  to  their  mode  of  action  it  is  possible  to  recognize  corrosive 
poisons,  which,  in  contact  with  the  tissues,  at  once  manifest  a  destructive 
tendency.  Irritant  poisons  cause  inflammation  without  actually  de- 
stroying the  tissues  which  they  irritate.  Other  toxic  agents — called 
by  the  toxicologists  neurotic  poisons — usually  give  rise  to  no  structural 
alteration  at  the  point  of  absorption,  but  on  entering  the  economy 
manifest  their  influence  through  the  brain  (cerebral  poisons)  or  spinal 
cord  (spinal  poisons),  or  both  (cerebrospinal  poisons);  they  may  or  may 
not  affect  the  organs  of  circulation  (cardiac  or  cardiovascular  poisons). 
That  this  classihcation,  commonly  accepted  by  toxicologists,  has  its 
limitations  is  shown  by  the  fact  that  arsenic  acts  on  the  mucosa  of  the 
alimentary  canal  as  an  intense  irritant  and  after  absorption  may  attack 
the  nerves  (arsenical  neuritis). 

Poisoning  may  be  acntc  or  cJironic,  and  the  same  agent  may  be  the 
cause  of  either  form.  In  large  doses  arsenic  produces  an  acute  poison- 
ing; small,  frer]uently  repeated  doses  cause  chronic  arsenical  poisoning. 
Similar  types  of  poisoning  are  produced  by  mercury,  lead,  phosphorus, 
copper,  arsenic,  etc' 

'  Brouardt'l,  "  Lcs  l7-^ri,\i(  riti.  .tk  i  ,irt,cnii-  iihi  ivt.1i.  ii-  I'li'.ri-  ct  nuTciirt'. 
plomb)."  Paris,  1904 


76  GENERAL    PATHOLOGY. 

Some  poisons  entering  the  system  give  rise  to  a  succession  of  phe- 
nomena to  which  the  term  intoxication  has  been  apphed.  Recogniz- 
ing that  within  the  ahmentary  canal  poisons  are  produced  the  absorp- 
tion of  which  causes  marked  symptoms,  Bouchard  promulgated  the 
term  autointoxication.  That  poisons  can  be  formed  in  the  alimentary 
canal  and  that  they  may  be  absorbed  and  exert  deleterious  influences 
on  the  tissues  has  been  fully  established.  Extended  knowledge  seems 
to  indicate  a  number  of  sources  from  which  such  poisons  could  arise. 
They  might  be  derived  from  (i)  imperfectly  digested  food,  (2)  result 
from  the  reabsorption  of  secretions  normally  present  in  the  intestine 
or  be  produced  by  the  action  of  the  intestinal  flora  on  (3)  food  or  (4) 
secretion,  or  (5)  on  both.  A  further  study  of  certain  forms  of  disease 
showed  that  definite  processes  might  arise  from  the  accumulation  in 
the  system  of  materials  that  should  be  excreted.  No  better  example 
of  this  is  seen  than  the  promptness  with  which  symptoms  follow  arrest 
of  renal  excretion. 

When  physiologic  inquiry,  by  modern  methods,  was  directed  to  the 
ductless  glands,  and  particularly  when  certain  diseases  of  these  struc- 
tures were  closely  investigated,  it  was  found  that  excessive  glandular 
activity  might  throw  into  the  circulation  a  quantity  of  secretion  with 
which  the  body  was  unable  to  cope,  thereby  giving  rise  to  manifesta- 
tions due  to  poisons  clearly  of  endogenous  origin  and  therefore  belong- 
ing to  the  autointoxications.  Such  toxic  bodies,  produced  by  cells, 
belong  to  the  group  of  substances  that  Prudden  has  designated 
histogenic  poisons. 

Further,  it  is  evidently  the  function  of  some  organs  to  destroy,  or 
render  inert,  certain  poisons  produced  by  the  tissues  and  normally  cir- 
culating in  the  blood  or  neutralized  at  their  sources.  Such  action  mav 
be  accomplished  by  the  direct  influence  of  gland  cells  upon  substances 
brought  to  them  or  by  a  secretion  manufactured  by  the  gland  and  poured 
into  the  circulation;  by  the  first  method  the  result  is  attained  in  the 
blood;  by  the  second  it  may  be  accomplished  in  the  circulation,  or  the 
blood  carrying  the  antidote  may  act  upon  the  poison  at  the  place  where 
the  latter  is  normally  produced.  It  is  evident  that  if  the  gland  in  ques- 
tion fail  to  perform  its  function  those  substances  which,  in  one  of  the 
ways  suggested,  it  would  normally  render  harmless,  may  accumulate 
in  the  organism  in  sufficient  quantity  to  manifest  toxic  properties.  ^ 
Here,  then,  was  another  group  of  poisons  arising  within  the  organism 
itself  and  causing  phenomena  that  could  with  proprietv  be  included 
among  the  autointoxications.  If  the  term  had  not  alreadv  lost  its  spe- 
cific value,  its  use  under  the  new  conditions  led  to  confusion  rather  than 
clearness. 

In  addition  to  the  difficulties  already  indicated  there  were  still  several 
groups  of  poisons  not  provided  for  by  existing  classifications.  When  any 
tissue  within  the  body  dies,  the  resulting  changes  which  it  undergoes  dur- 
ing the  process  of  removal  are  associated  with  the  production  of  toxic 
agents ;  these  substances  Adami  calls  disintegrative  endogenous  poisons. 
If  hemorrhage  occur  in  the  tissues,  disintegration  of  the  blood  liberates 
bodies  which,  entering  the  circulation,  may  exert  a  toxic  action.  There  is 
reason  to  believe  that  the  death  of  any  cell  liberates  noxious  materials  for 

^  See  Addison's  Disease,  chapter  on  Diseases  of  the  Adrenal,  also  Myxedema, 
(^•ctinism,  etc.,  in  chapter  on  Diseases  of  the  Thvroid. 


DISEASE.  77 

which,  in  nurnial  iiiumtities,  adecjuate  j^rovision  is  niaile.  When,  how- 
ever, cell  or  tissue  death  exceeds  certain  limits,  the  mechanism  whuh, 
during  health,  converts,  renders  inert,  or  excretes  the  resulting  cataholic 
product  is  overwhelmed  ami  the  accumulated  poison  manifests  its  pres- 
ence by  phenomena  possessing,  in  some  instances,  fairly  constant  char- 
acters. It  is  the  absorption  of  such  dead  material  that  accounts  for 
the  aseptic  fever  following  injuries  (fracture  of  bone)  with  which  bac- 
terial influences  apparently  have  nothing  to  do.  Attention  has  already 
(p.  71)  been  called  to  the  evidence  of  poison  production,  absorption, 
and  definite  action  on  the  viscera  when  the  surface  of  the  body  has  been 
injured  by  heat.  The  exact  nature  of  all  such  toxic  substances  is  ob- 
scure; we  see  the  results  of  their  action  without  possessing  any  accurate 
knowledge  as  to  their  composition,  mode  of  influence,  or  ultimate  fate. 

There  are  still  two  groups  of  poisons  produced  in  the  body  and  dif- 
fering in  their  mode  of  production  from  any  of  the  foregoing;  these  are 
the  parasitic  poisons,  which  may  further  be  subdivided  into  those  due  to 
or  arising  from  (a)  animal,  (b)  vegetable  parasites  present  in  the  host. 
The  parasitic  poisons  will  be  more  specifically  considered  with  diseases 
caused  by  bacteria  and  animal  parasites. 

The  foregoing  attempt  to  show  how  complex  has  become  the  problem 
of  the  proper  classification  of  poisons  indicates,  in  part  at  least,  the 
difticulty  in  formulating  a  systematic  presentation  of  the  subject.  Of 
the  various  classifications  that  have  been  offered,  the  writer  is  unfamiliar 
with  any  that  is  superior  to  that  suggested  by  Adami.  '  It  covers  the 
essential  groups  to  which  reference  has  already  been  made  and  I  take 
the  liberty  of  quoting  it  in  full: 

(i)  EXOGENOUS. 

Due  to  thf  actions  of  poisons  entering  the  system  from  without. 

i.    Exotic  or  introduced:    due  to  the  action  of  substances  foreign  to  the 
organism,  which  gain  entrance  through  the  skin,  the  digestive,  the 
respiratory  or  the  genito-urinary  tract. 
li.  Indigenous  or  excretory. 

(a)   Indirect  autointoxication,  due  to  the  absorption  of  retained  ex- 
creta. 
(6)    Disintegrative,  due  to  the  absorption  of  decomposition  and  fer- 
mentation   products    developed    in    the    external    secretions 
through  the  action  of  those  secretions. 

(2)  ENDOGENOUS. 

i.  Direct  autointoxication. 

{a)  Internal  secretory,  due  to  the  action  of  excessive  or  unneutralized 
or  modified  discharges  from  the  cells  of  one  or  other  tissue 
acting  directly   upon   the   other  tissues  of  the   body   with<.>ut 

i)revious  discharge  from  the  system. 
lisintegrativc,  due  to  the  action  of  the  products  of  decompo- 
sition and  necrosis  of  one  or  other  tissues  acting  in  a  similar 
manner. 

ii.  Parasitic. 

(a)   Micro  parasitic,  the  infections. 

(h)   Macro  parasitic,  poisons  from  animal  parasites. 

It  has  been  shown  with  regard  to  many  poisons  that  the  action  is 
essentially  chemical,  and  this  is  probably  true  of  all.     By  disturbing 

'  ■■  .American  Medicine."  Julv  ■■-     •■  -  •    •      ■  -  ■ 


78  GENERAL    PATfiOLOGY. 

the  normal  chemistry  the  function  is  necessarily  perverted  or  arrested 
and  the  structure  sooner  or  later  yields  to  the  abnormal  influence.  The 
recognition  that  the  action  of  a  given  poison  is  almost  certainly  a  chemic 
problem  at  once  offers  an  explanation  for  phenomena  otherwise  most 
obscure.  A  poison  exerts  its  influence  by  combining  with  the  first  suit- 
able substance  with  which  it  comes  in  contact.  This  elective  action  of 
poisons  is  shown  by  the  combination  of  silver  salts  with  albumens  and 
bv  the  local  action  of  a  number  of  poisons  which  destroy  tissue  at  the 
point  of  contact  and  are  themselves  at  the  same  time  rendered  inert. 
Other  poisons  pass  beyond  the  external  barriers  upon  which,  in  some 
mstances,  they  exert  no  injurious  influence.  Carbonmonoxid  manifests 
no  irritative  action  on  the  respiratory  passages,  but,  entering  the  blood, 
combines  with  the  hemoglobin  so  intimately  that  the  latter  loses  its 
power  to  carry  on  the  normal  oxygen  and  carbondioxid  exchange.  In 
chronic  arsenical  poisoning  the  metal  shows  a  special  affinity  for  keratin, 
and  may  be  demonstrated  in  the  hair,  nails,  and  in  the  nervous  system 
(neuro-keratin).  The  tendency  of  lead  to  attack  the  peripheral  nerves 
(lead  neuritis)  rests  upon  a  similar  chemic  basis.  Although  conclu- 
sive evidence  is  wanting,  there  seems  no  reason  to  doubt  that  the  thera- 
peutic action  of  many  drugs  can  be  satisfactorily  accounted  for  in  no 
other  way;  the  influence  of  cerebral  sedatives  and  the  action  of  such 
medicaments  as  strychnin  are  most  easily  explained  by  the  assumption 
that  they  effect  a  more  or  less  temporary  combination  with  certain  cells 
of  the  central  nervous  system.  The  modern  view  of  acquired  immunity  ^ 
is  based  on  the  conviction  that  certain  bacterial  toxins  combine  with 
cells,  and  it  has  been  shown  experimentally  that  tetanus  toxin  in  an 
emulsion  of  tissue  from  the  central  nervous  system  is  carried  down  by 
the  sediment,  leaving  the  supernatant  fluid  relatively  non-toxic;  in 
other  tissues  or  cell  suspensions  the  toxin  is  not  similarly  anchored. 
Toxicologists  are  familiar  with  the  fact  that  after  various  forms  of 
poisoning  the  toxic  agent,  postmortem,  can  be  found  in  largest  quanti- 
ties in  certain  organs,  particularly  the  liver,  brain,  spleen,  and  kidneys. 
That  any  poison  is  more  abundant  in  a  given  tissue  than  in  the  blood 
clearly  establishes  that  some  local  influence  extracts  it  from  the  circu- 
lating fluid  and  anchors  it  in  the  new  position.  There  is  nothing  so 
very  extraordinary  in  this  fact  if  it  be  recalled  that  in  the  organization 
of  normal  bone  the  developing  tissue  must  possess  a  higher  affinity  for 
lime  salts  than  the  other  tissues  or  the  blood,  which  clearly  must  present 
to  all  structures  the  same  general  proffer;  each  elects  the  substance 
suited  to  its  particular  needs.  I  do  not  recall  who  was  responsible  for 
the  crystallized  truth,  that  cells  are  not  nourished,  they  nourish  them- 
selves; it  is  equally  true  that  they  are  not  poisoned,  they  poison  them- 
selves. 

The  elective  affinity  of  carbonmonoxid  for  hemoglobin,  while  arrest- 
ing the  function,  does  not  seem  fraught  with  any  immediate  danger  to 
the  cell.  Other  substances,  however,  combine  with  and  promptly  de- 
stroy the  erythrocyte.  The  process  is  properly  termed  erythrocytolysis, 
but  brevity  and  convenience  have  led  to  the  adoption  of  the  word 
hemolysis.  '  The  suT)stance  producing  the  cell  change  is  called  an 
erythrocytolysin  or  hemolysin.     Potassium  chlorate,   arseniuretted  hy- 

^  See  Theories  of  Immunity,  during  the  discussion  of  which  this  subject  is 
again  reviewed  from  a  somewhat  different  aspect. 


DISEASE.  7') 

drogen,  toluvlencdiamin.  arc  hemolytic.  The  inlroduction  into  the  cir- 
culation of  blood  derived  from  an  animal  of  another  species  is  promptly 
followed  by  hemolysis,  the  introduced  blood  rapidly  disappearing  and 
the  blood  of  the  animal  experimented  upon  also  suffering  to  a  more  or 
less  marked  degree.  That  certain  bacteria  produce  hemolysins  is  now 
fullv  established.  Among  the  organisms  whose  poisons  contain  hemo- 
lytic substances  mav  be  mentioneil  streptococci,  certain  of  the  staphylo- 
cocci. Bacillus  pyocyaneus.  Bacillus  dii)htheria;.  Bacillus  tetani,  and 
Bacillus  typhosus.  Certain  animal  parasites  are  the  source  of  hemo- 
lytic bodies.  Red  cell  destruction  is  ])rescnt  in  a  varying  degree  in 
practically  all  forms  of  malaria,  and  constitutes  one  of  the  most  con- 
spicuous features  of  that  type  called  "blackwater"  fever;  in  this  form 
the  destruction  of  red  cells  may  be  so  marked  that  the  plasma  of  the 
blood  is  tinged  and  the  blood  coloring-matter  poured  out  from  the  kid- 
nev  in  such  quantities  that  the  urine  is  highly  colored,  by  reason  of 
which  fact  the  condition  has  received  the  name  hemoglobinuric  malaria, 
or  malaria  haematuria.  In  cattle  the  intracellular  ])arasite  (Piro- 
plasma  bigeminum)  causing  Texas  fever  is  actively  hemolytic.  At 
present  it  seems  highly  probable  that  the  anemias  caused  by  the  Di- 
bothriocephalus  latus  and  the  uncinaria  result  from  the  action  of  hemo- 
lytic poisons  secreted  by  the  parasites.  The  poisons  of  snakes  contain 
hemolvtic  substances.  '  Flexner  and  Noguchi  have  also  shown  that 
venonis  contain  a  number  of  cytolysins,  and  that,  aside  from  the  hemo- 
lytic poisons,  there  are  substances  that  attack  the  parenchymatous 
cells  of  a  number  of  organs. 

The  foregoing  review  of  a  small  number  of  the  many  poisons  known 
to  attack  the  red  blood-cell  indicates,  in  a  general  way,  the  character  of 
the  toxic  agents  that  may  attack  the  somatic  cells.  It  has  been  pos- 
sible to  demonstrate,  for  a  large  number  of  the  body  cells,  poisons  the 
action  of  which,  if  not  specific,  closely  approaches  that  quality.-  Hepa- 
tolysins  attack  particularly  the  liver"  cell,  nephrolysins  the  renal  paren- 
chvma;  Flexner  and  Noguchi  conclude  that  the  hemorrhages  seen  in 
rattlesnake  poisoning  are  due  to  the  action  of  a  cytolysin  which  they 
call  hemorrhagin,  affecting  particularly  the  endothelium  of  the  blood- 
capillaries.  The  field  of  cell  intoxication  or  destruction  is  but  .super- 
ticiallv  ex})lored,  and  this  conception  of  the  action  of  poisons,  and  an 
extended  information  concerning  immunity,  promise  limitless  progress 
in  our  knowledge  of  morbid  processes.  Many  so-called  neuroses  and 
diseases  now  regarded  as  "functional"  may  be  traced  to  the  action  of 
subtle  ])oisons  the  origin  of  which  we  may  hope  to  lay  bare.  Bell '  has 
recently  written  a  most  interesting  paper  on  the  relation  of  endogenous 
poisons  to  mental  disturbances. 

'Sec  paper  bv  McFarlanfl.  •  Phila.  Med.  Jour.."  Feb.  15.  1902;  Flexner 
and  Noguchi,  '•  Univ.  of  Penna.  Med.  Bull."  1Q02.  xiv,  43S;  "Jour,  of  Exper. 
Med.,"  1902.  vi,  277:  "Univ.  of  Penna.  Med.  Bull.,"  Nov..  1902.  Svmposium 
on  Serpent  Venoms,  "  Proc.  of  the  Path.  Soc.  of  Phila.,"  Feb.,  1903.  Lamb  and 
Hunter,  ••  Lancet,"    1904,  vol.   ii.      Flexner  and   Noguchi,    "Jour,   of  Path.  an<l 

Bact."  vol.  x,  p.  1 1 1.  •,,,-•.        J       u 

*  The  literature  of  this  suV)ject  is  voluminous  and  widelv  distributed;  the 
reader  will  be  able  to  trace  the  most  important  articles  and  glean  essential  facts 
from  paper  bv  Pearce.  •loumal  of  Med.  Research."  1904.  vol.  xii,  p.  i:  also  con- 
suh  Vaughan  and  Novy,  Cellular  Toxins,"  4th  ed.,.1902;  Herter,  "Chemical 
Pathology*-." 

'"lour.  Amer.  Med.  Assoc."  Feb.  20.  1904.  p.  507. 


8o  GENERAL    PATHOLOGY. 

Before  dismissing  the  poisons  as  causes  of  morbid  processes  it  is 
necessary  to  note  the  occurrence,  in  pregnant  women,  of  a  form  of 
endogenous  intoxication  known  by  obstetricians  as  the  toxemia  of 
pregnancy.  During  gestation,  under  conditions  at  present  imper- 
fectly understood,  there  arises  a  series  of  phenomena  strongly  suggest- 
ing the  presence  of  one  or  more  powerful  poisons.  The  exact  nature, 
origin,  and  ultimate  fate  of  the  toxic  substance  or  substances  remain 
obscure.  Ewing  believes  that  the  metabolic  disturbance  depends  upon 
deficient  oxidizing  capacity  on  the  part  of  the  liver,  which  fails  to  combine 
the  proteid  derivatives  to  form  urea.  Among  the  manv  manifestations 
of  this  peculiar  toxemia  may  be  mentioned  cutaneous  disturbances, 
ptyalism,  the  nausea  and  vomiting  of  pregnancy,  jaundice,  albuminuria, 
fatty  degeneration  and  other  disturbances  of  the  liver,  and  eclampsia 
independent  of  or  with  albuminuria;  the  symptomatologv  indicates 
the  presence  of  some  intensely  toxic  substance,  possibly  a  number  of 
poisons.  ^  It  is  possible  that  the  insanities  of  pregnancy  have  a  similar 
origin.  In  the  severer  forms  of  toxemia  the  liver  appears  to  bear  the 
brunt  of  the  injury,  although  kidney  lesions  are  present  in  over  ninety 
per  cent,  of  the  cases. 

The  influence  of  certain  internal  secretions  in  maintaining  body 
nutrition,  and  the  important  nutritional  disturbances  resulting  from 
excess  as  well  as  inadequacy,  will  be  discussed  when  dealing  with  the 
special  pathology  of  the  particular  organs  producing  these  secretions; 
hyperthyroidism  and  athyroidism  will  be  discussed  with  diseases  of  the 
thyroid,  Addison's  disease  with  the  adrenals,  etc. 

^See  papers  by  Davis,  "Amer.  Jour,  of  the  Med.  Sci.,"  Feb.,  1905;  Stone, 
"Amer.  Gynecol.,"'  Dec,  1903,  p.  518;  Ewing.  "Amer.  Jour,  of  Obstet.."  1905, 
vol.  li.  No.  2. 


CHAPTER    III. 
BACTERIA  AS  CAUSES  OF  DISEASE. 

GENERAL  CONSIDERATIONS. 

Near  the  bottom  of  the  scale  of  vegetable  life  may  be  recognized 
three  groups  of  microorganisms  which,  in  a  general  way  following 
.\ageli,  may  be  divided  into  (i)  the  Schizomycetes.  fission  fungi,  or 
bacteria;  (2)  Blastomycetes.  saccharomycetes,  yeasts  or  yeast  fungi, 
or  budding  fungi;  (3)  Hyphomycetes,  molds,  mold  fungi,  or  mucorini, 
and  sometimes  called  the  branching  fungi.  This  classification  is  open 
to  important  objections  and  must  be  regarded  as  provisional;  it  serves 
the  purpose  of  labeling,  facilitates  grouping,  and  in  other  ways  aids 
our  study  of  these  parasites  and  the  diseases  caused  by  them.' 

BACTERIA.^ 

Bacteria  are  microscopic,  unicellular  organisms  of  vegetable  origin. 
Thev  varv  in  size  from  ultramicroscopic  bodies,  too  small  for  demonstra- 
tion by  optical  appliances  at  present  at  our  disposal,  to  larger  units 
the  ma.ximum  length  of  which  may  exceed  the  diameter  of  a  red  blood - 
cell.^  From  eight  to  twelve  of  the  medium-sized  cocci  can  be  placed 
in  a  row  across  the  surface  of  an  erythrocyte.  The  smallest  demon- 
strable object  by  the  best  modern  microscopes  measures  about  0.2,"; 
a  number  of  bacteria  are  more  minute.* 

Structure. — Bacteria  consist  of  a  non-chlorophyllous  protoplasm, 
which,  in  some  forms,  is  condensed  at  the  periphery,  giving  rise  to  a  layer 
resemliling  a  cell  wall;  a  few  possess  outer  cellulose  membranes  and 
some  are  encapsulated.  Butschli  has  shown  that  the  pla.sma  of  bac- 
teria is  a  coagulable  gelatinous  substance  which  may  be  expressed  from 
the  interior  of  the  cell.  He  recognized  in  most  bacteria  an  outer  mem- 
brane which  does  not  stain  and  a  faintly  tingible  adjacent  zone,  while 

'  It  is  not  the  purpose  of  this  work  to  discuss  systematically  the  orj;anisms 
that  cause  disease.  The  student  is  referred  to  numerous  excellent  works  on 
bacteriologv.  among  which  may  be  mentioned  Kolle  and  Wassermann.  "  Hand- 
buch  der  Nlikroorganismen ':  "  Flugge,  "Die  Mikroorganismen."  iSo<>  edition; 
.Mace.  "Traite  dc  Bacteriologie."  1901,  4th  edition,  with  Atlas;  Mifjuel  and  Cam- 
bier.  "Traite  de  Bacteriologie  Pure  et  Appliqude."  1902;  .Vluir  and  Ritchie. 
•'Manual  of  Bacteriologv,"  American  edition,  edited  by  Harris;  Sternberg, 
•Text-book  of  Bacteriology";   .McFarland.  "Text- book  of  Pathogenic  Bacteria." 

*  In  the  present  edition  the  chapter  on  Bacteriologie  Technic  has  been  placed 
near  the  end  of  the  volume. 

^  The    measurement    of   bacteria    is   usually    made     in     microns.     The     term 

"micron"  is  an   abbreviation   for  micromillimeter.  which  is  the  one-thousandth 

part  of  a  millimeter;    in  other  words,  about  the  twenty-five  thousandth  part  of 

an  inch.     The  word    •micromillimeter."  or    'micron,"  is  practically  never  written 

out,  but  is  indicated  V)v  the  Greek  letter /«. 

*  For  review  of  the  ultramicroscopic  bacteria  see  Roux,  •Bulletin  de  I'lnstitut 
Pasteur."  1Q03.  \f<\.  i.  Nos.  i  and  2;  Hcktoen.  " Jour.  Amer.  Med.  Assoc.."  Aug. 
I  ;  and  22,  1903. 

7  Si 


82  GENERAL    PATHOLOGY. 

near  the   center  is   an   area   staining  intensely   and,   though   probably 
not  a  nucleus,  possessing  some  of  the  characters  of  that  structure. 

Motility, — Many  bacteria  possess  the  power  of  locomotion.  Motile 
cocci,  bacilli,  and  rigid  spirals  are  propelled  by  the  exceedingly  rapid 
vibratory  motion  of  thin,  lash-like  processes,  extending  from  the  side  or 
poles  of  the  organism,  called  fiagella.  (For  the  demonstration  of  flagella 
see  chapter  on  Bacteriologic  Technic.)  Certain  of  the  flexible  spirilla 
possess  the  power  of  moving  from  place  to  place  by  (i)  a  rotatory 
motion  in  their  long  axis,  or  (2)  by  an  undulator}-  or  snake-like  move- 
ment. 

Reproduction  of  the  schizomycetes  is  principally  by  the  process  of 
fission:  i.  e.,  a  cell  having  reached  its  full  development,  simply  divides 
into  two  or  more  segments.  Reproduction  also  takes  place  by  spore 
formation.  Two  kinds  of  spores  have  been  described:  (i)  Arthrospores 
and  (2)  endospores. 

Arthrospore  formation  is  described  by  de  Bary  and  Hueppe  as  occur- 
ring in  cocci.  In  certain  chain  cocci  there  are  a  few  cell  elements  that 
acquire  those  characteristics  common  to  spores  without  any  apparent 
diflFerentiation  of  cell  protoplasm.  They  appear  larger  than  the  other 
elements  of  the  chain;    their  borders  are  more  sharply  defined,   and 

the  cell-wall  appears  to  be  thicker;  they  possess  a  much 

greater  resistance  than  the  other  cells  to  all  conditions 

"^  incompatible  with  life,  and  their  protoplasm  is  darker 

..^^  or   more   highly  retractile.     When  these  bodies   are 

~  —  removed    from    conditions   that   brought    about   the 

—  ■"  death  of  the  other  chain  elements,  and  when  placed 

in   favorable   soil,    they    develop    the    characteristic 

^^^' BY^'Fiss^oN^—tcop-     chains.     This  type  of  spore  formation  is  not  univer- 

lin  and  Bevan.)  sally  acccptcd ;   the  bodies  thought  to  be  arthrospores 

have  no  enveloping  membrane,  are  without  charac- 
teristic stain  reaction,  and  it  is  not  known  that  the}'  possess  increased 
resistance  to  destructive  agencies. 

Endospore  formation  is  the  development  within  the  bacterial  cell  of 
spheric  or  oval  bodies  possessing  unusual  resistance  to  conditions  incom- 
patible with  the  life  of  the  mature  organism.  Usually  the  spores  make 
their  appearance  only  when  germ  plasma  manifests  degenerative  changes 
and  becomes  granular.  The  spore  appears  at  first  as  a  small,  bright 
point,  which  gradually  increases  in  size  until  its  diameter  may  exceed 
that  of  the  parent  cell.  Frequentl}^  the  spore  develops  in  the  center 
of  the  organism,  when,  if  the  microbe  is  a  bacillus,  it  may  appear 
spindle-shaped.  If  the  spore  arises  at  one  of  the  poles  of  a  bacillus, 
the  organism  will  appear  club-shaped  or  pendulum-like — a  character- 
istic of  the  Bacillus  tetani.  Endogenous  sporulation  is  an  attribute 
of  bacilli  and  a  few  spirilla,  although  Zopf  has  described  the  formation 
of  endospores  in  certain  micrococci,  and  Escherich  in  the  Sarcina 
pulmonum.  It  is  generally  believed  that  spore  formation  should  not 
be  regarded  as  a  process  of  multiplication,  but  rather  as  a  stage  in 
the  perpetuation  of  the  organism.  Usually  sporulating  bacteria  do 
not  manifest  the  tendency  except  in  the  presence  of  conditions  un- 
suited  to  continued  proliferation, — a  fact  strongly  suggesting  that  the 
process  is  directed  toward  establishing  heightened  resistance  to  ex- 
ternal  agencies.      Under  favorable   conditions,   spores   always   develop 


BACTERIA  AS  CAUSES  OF   DISEASE.  83 

into    organisms     identical     witli     those     from    which    tlicy    were    de- 
rived.' 

The  jirocesses  ot  reproduction,  as  seen  in  yeasts  and  molds,  are 
described  and  illustrated  with  those  fungi. 

It  is  impossible  to  tlistinguish  between  the  many  species  of  any 
one  kind  of  organism  by  morphologic  peculiarities  alone,  therefore  the 
biologic  characteristics  must  be  developed  to  serve  as  a  guide  to  satis- 
factory identification.  It  is  well  known  that  several  varieties  of  the 
micrococcus  pyogenes  are  morphologically  identical,  and,  were  it  not 
for  certain  biologic  peculiarities,  it  would  be  impossible  to  differentiate 
one  from  another.  Those  points  commonly  worked  out  will  be  found 
tabulated  in  the  chapter  on  Bacteriologic  Technic. 

Microorganisms  forming  pigment  in  the  process  of  growth  are  known 
as  chromogenic  bacteria,  or  chromogens.  Breyerinck  and  Schroter  divide 
the  chromogenic  luicteria  into  (i )  chromoparous,  in  which  the  coloring- 
matter  surrounds  the  colorless  organism  and  is  apparently  a  secretion 
of  the  germ;  (2)  the  chromophorous,  in  which  the  cell 
protoplasm  is  pigmented,  and  (3)  the  parachromophor- 
ous,  those  containing  colored  granules  in  the  cell  wall.  i  l|;  C 

Zymogenes,    or    zymogenic    bacteria,    are    those  ^       g 

capable  of  inducing  fermentation.  p^^     .„.-Fro«    ccl- 

Saprophytic  bacteria  are  those  incapable  of  produc-  tcre  of  baollus 

ing  disease.     Such  organisms  subsist  on  dead  animal     sho^^rd^'iopmcn,  of 
or  vegetable  matter  and  may  be  present  in  a  gan-  spores    within    the 

grehous  limb  or  blood-clot  in  the  uterus,  but  are  not  cT""  o  p l^'which. 

able  to  invade  the  living  tissues.     While  this  distinc-  )f,'^J;,^"'thc  s^r^'' 

tion     between    saprophytism    and     parasitism    may  on     the    extreme 

sometimes   hold,  it  cannot    be  applied   too   strictly.  Thw  badiii  dc"*" 

Theobald    Smith-    suggests    that    many    pathogenic  s£^.-(Co*;i« 

l)actena  mav  at  some  time  have  been  saprophytic.  andBnan.)    x  800 

Pathogenesis. — Pathogenic  bacteria  are  the  disease-  '  '*""^'^"- 

producing    organisms.       Koch    has    formulated,    as 
conclusive  evidence  of  the  specificity  of  a  given  organism,  the  following 
requirements,  which  must  be  met : 

1 .  The  organism  vmst  he  present  in  all  eases  of  the  disease. 

2.  It  must  be  grown  in  pure  culture. 

3.  //  must  produce  the  disease  by  inoculation  in  susceptible  animals. 

4.  From  such  animals  the  germ  must  be  obtained  and  again  cultivated 
in  pure  culture. 

To  this  cycle  of  proof  has  recently  been  added  another  demand  for 
experimental  evidence  of  pathogenicity. 

5.  From  cultures  of  the  organism  there  should  be  demonstrated  a 
toxin  that,  without  the  germ,  will  produce  the  phenomena  of  the  dis- 
ease, or  by  means  of  which  an  antitoxin  or  immunizing  substance  can 
be  developed  in  susceptible  animals,  lessening  or  removing  their  liability 
to  the  disease  presumed  to  be  produced  by  the  organism  in  question. 

Any  evidence  less  conclusive  than  that  afforded  by  the  foregoing  re- 
quirements may  be  considered  as  presumptive  knowledge  of  specificity. 
So  manv  diseases  occur  in  man  and  not  in  lower  animals  that  the  best  we 
can  hope  to  do  in  such  cases  is  to  produce,  by  experiment  or  otherwise, 

•  For  recent  paper  on  sponilation  in  anthrax  and  other  sporc-Vx-arins  bac- 
teria see  Selter.  'Centralbl.  f.  Bakt.,"  Oct.  17.  1904.  p.  186. 

-  •Jour,  of  the  Boston  Soc.  of  Med.  Sci.."  xgoo,  vol.  iv.  p.  95. 


84  GENERAL    PATHOLOGY. 

as  much  of  the  proof  as  possible,  and  to  accept  the  germ  as  the  cause 
in  the  absence  of  any  equally  or  more  rational  explanation.  In  some 
diseases — for  example,  leprosy — this  is  practically  the  stage  at  which 
the  scientific  inquiry  at  present  rests.  It  is  also  most  important  to 
recognize  that  the  disease-producing  power  of  well-known  pathogenic 
organisms  is  by  no  means  always  the  same.  Some  bacteria  under 
cultivation  entirely  lose  their  ability  to  produce  disease  even  in  suscep- 
tible animals.  Saprophytic  bacteria  under  unusual  conditions  may 
occasionally  become  pathogenic,  and  it  is  highly  probable  that  some 
pathogenic  forms  have  acquired  this  faculty. 

Toxicogenic  Bacteria. — Certain  bacteria  are  endowed  with  the  prop- 
erty of  elaborating  poisonous  bodies  without  themselves  being  able  to 
exist  in  the  living  tissues.  As  will  be  pointed  out  later,  all  disease- 
producing  bacteria  are  toxicogenic  to  a  certain  degree. 

Liquefaction. — Those  bacteria  that  in  their  growth  liquefy  Koch's 
fIesh-pe|)tone-gelatin  are  known  as  liquefying.  They  probably  elaborate 
a  ferment  having  this  property.  The  exact  ferment  to  which  this  lique- 
faction is  due  is  a  member  of  the  proteolytic  enzymes.  Organisms  not 
having  this  property  are  known  as  the  nonliquefying  bacteria. 

The  power  of  producing  gas  is  marked  in  some  forms  of  bacteria  and 
is  absent  in  others.  Gas  production  is  a  conspicuous  feature  of  certain 
anaerobic  organisms,  among  which  may  be  mentioned  the  bacillus  of 
tetanus  and  some  of  the  bacteria  giving  rise  to  gaseous  abscesses  and 
gangrene.  A  number  of  the  intestinal  bacteria  produce  gas,  and  the  useful- 
ness of  yeasts  in  the  arts  depends,  to  a  large  degree,  upon  this  quality. 
Of  the  numerous  gases  produced  by  the  growth  of  bacteria,  carbonic 
acid  is  the  most  common. 

Some  bacteria  coagulate  milk,  and  this  may  be  used  as  a  test  in 
studying  species. 

Stain  Reaction. — Many  bacteria  possess  more  or  less  constant  stain  re- 
actions, and  a  few  microorganisms  are  identified,  in  part  at  least,  by  their 
taking  certain  dyes  or  staining  by  certain  methods.  The  special  methods 
are  given  with  each  organism,  but  the  following  list  of  bacteria,  with  their 
reactions  to  Gram's    method,  is  introduced  for  convenient  reference:^ 

Slainctl  by  Gram's  Mclhod.  Not  stained  by  Gram's  Method. 

Bacillus  diphtheria;.  Bacillus  pyocyaneus. 

Bacillus  pseudodiphtheri;c.  Bacillus  typhosus  (and  group). 

Bacillus  anthracis.  Bacillus  coli  (and  group). 

Bacillus  tetani.  Bacillus  anthracis  symptomatici. 

Bacillus  leprae.  Bacillus  mallei. 

Bacillus  aerogenes  capsulatus.  Bacillus  ulceris  mollis. 

Bacillus  (xdematis  maligni  (in  tissues      Bacillus  dysenteriae. 

usually  positive) .  Proteus  vulgaris. 
Diplobacillus  of  Morax  and  Axenfeld.      Bacillus  rxdematis  maligni   (in  films  usu- 
Bacillus  tuberculosis.  ally  negative). 

Bacillus  xerosis.  Bacillus  influenzte. 

Actinomyces.  Diplococcus  intracellularis  meningitidis. - 

Pneumococcus.  Pneumobacillus  (Friedlander). 

Streptococcus.  Gonococcus. 

Staphylococcus  pyogenes  aureus.  Spirillum  cholene  Asiaticse. 

Staphylococcus  p^-ogenes  albus.  Bacillus  pestis. 

Staphylococcus  pyogenes  citreus.  Bacillus  icteroides. 
Micrococcus  tetragenus. 

^  For  method  see  chapter  on  Bacteriologic  Technic. 

^  Recent  studies  of  the  meningococcus  show  that  the  reaction  of  this  organ- 
ism to  Gram's  method  cannot  be  depended  upon  for  differentiating  it  from  the 
pneumococcus. 


UACTKKIA    AS   CAUSES  OF   DISK  ASK.  S5 

Thermal  Death-point.  -Ivacli  organism  has  what  is  known  as  its 
optimum  temperature,  at  whii-h  tlie  growth  is  most  luxuriant  and  a!  ■  •  • 
or  below  which  it  becomes  less  and  less  free  as  the  change  ])rogri-  • 
Eventually,  temperatures  are  reached  so  high  or  .so  low  that  growth  is 
arrested.  Cold  does  not  kill,  but  a  surticiently  high  temi)erature  de- 
stroys any  germ.  The  exact  temperature  proving  tiestructive  to  viability 
is  known  as  the  thermal  death-point.  As  moist  heat  and  dry  heat  are  not 
equally  efficacious,  each  will  have  its  own  thermal  death-point.  Cul- 
tures in  different  media  and  of  different  ages  often  show  marked  differ- 
ences in  the  temperature  necessary  to  kill.' 

Aerobic  and  anaerobic  ■  are  terms  introduced  by  Pasteur  to  denote 
that  an  organism  requires  the  presence  or  absence  of  oxygen  as  an 
essential  to  its  growth.  It  was  proposed  at  one  time  to  classify  bac- 
teria upon  this  basis,  dividing  them  into  two  groups, — aerobic  and  an- 
aerobic,— but  it  was  soon  discovered  that  certain  organisms  might  be 
cultivated  either  in  the  presence  or  absence  of  air,  though  such  bacteria 
usually  showed  a  preference  for  one  or  the  other  condition.  This  led 
to  the' introduction  of  the  terms  facultative  and  obligate.  An  oblif^atc 
ori^aiiis))!  requires  absolutely  one  or  the  other  condition.  A  faciiltathr 
ori^auisni.  while  showing  a  marked  preference  for  one  condition,  may 
develop  under  the  other.  Although  the  hope  of  thus  classifying  bac- 
teria has  been  al»andoned,  the  terms  are  retained,  and  are  now  used 
for  the  puqjose  of  description  as  well  as  aids  to  identification. 

Photogenesis. — Many  bacteria  are  endowed  with  the  power  of  pro- 
ducing phosphorescence. 

The  faculties  of  producing  color,  fermentation,  disease,  etc.,  are 
simply  properties,  and  one  or  all  may  be  possessed  by  a  single  organism. 
Furthermore,  an  organism,  under  varying  conditions,  may  be  chromo- 
genid  or  nonchromogenic,  zymogenic  or  nonzymogenic.  aerobic  or  an- 
aerobic, pathogenic  or  nonpathogenic.  Again,  a  l)acterium  that  is 
pathogenic  for  one  animal  may  be  wholly  destitute  of  this  property 
when  injected  into  an  animal  of  another  species. 

Other  Bacterial  Products.-^ — In  the  process  of  proliferation  an<l 
growth  bacteria  abstract  from  the  surrounding  media  certain  bodies 
that  enter  into  and  become  a  part  of  the  chemistry  of  the  organism. 
After  subserving  a  useful  purpose  in  the  economy  of  the  cell  and  under- 
going important  changes,  many  of  these  bodies  are  liberated.  Not 
only  are  certain  bodies  elaborated  within  the  cell,  but.  as  a  result  of  ab- 
stracting certain  elements  from  the  surrounding  medium,  the  chemistry 
of  the  nutrient  is  changed.  If  the  elements  taken  up  by  the  gemi  and 
utilized  as  food  are  thrown  off  by  the  cell,  and  again  enter  the  surround- 
ing medium,  they  no  longer  possess  the  same  chemic  affinities,  and 
hence  do  not  form  again  the  same  molecular  combinations.  As  these 
products  are  to  a  certain  extent  dependent  upon  the  character  of  the 
nutrient,  it  can  be  understood  that  the  growth  of  a  given  germ  upon 
different  media  may  to  some  degree  modify  its  products.  Different 
bacteria  growing  upon  the  same  medium  elaborate  substances  dissim- 

'  For  method  sec  chapter  on  Bacteriol-iKic  Technic. 
•  For  methods  of  demonstration  see  ehai'ter  on  BacterioloKic  Technic. 
^  For  an    exhaustive   review  of   bacterial  products  sec  Vaughan  and  N'«'\  \ 
"Cellular  Toxins."  4th  edition.    1902:    also  Oppenheimer.  "  Toxine  tmd 

tiivillf    "    T<TT.-i      I1104. 


86 


GENERAL    PATHOLOGY, 


ilur,  chemically  and  physiologically,  and  the  same  organism  on 
different  media  may  yield  other  products.  The  bacillus  typhosus  in 
meat  infusions  produces  a  poisonous  alkaloid,  in  peptone  solutions 
it  does  not.  Within  certain  rather  wide  limits  each  organism  produces 
one  or  more  bodies  as  characteristic  of  its  growth  as  the  alkaloids  of 
certain  vegetable  forms  of  a  higher  type.  Of  the  ultimate  chemistry 
of  many  bacterial  products  little  is  known ;  we  deal  more  with  the  results 
of  their  activity  than  with  the  bodies  themselves. 

Among  the  important  products  of  bacterial  life  are  soluble  ferments, 
or  enzymes/  These  are  thrown  off  from  the  cell,  and,  entering  the 
surrounding  medium,  induce  chemic  changes,  which  are  probably  di- 
rected toward  a  kind  of  predigestion,  which  enables  the  growing  germ 
to  obtain  nourishment  that  previously  was  not  in  an  assimilable  form. 
Certain  of  these  ferments  split  up  starch  in  a  manner  resembling  diastase, 
and  hence  they  are  called  diastatic  or  ainylolytic  jerments,  in  their  action 
resembling  the  ferments  normally  present  in  the  saliva  and  pancreatic 
secretion. 

Other  enzymes  break  up  the  proteids,  converting  albumin  into 
albumose  and  into  peptone,  and  hence  they  are  called  peptonizing  or 
proteolytic    jerments.     Others    break    up    fat    (lipolytic    ferments),    and 

some  possess  the  property  of  con- 
verting cane-sugar  into  glucose  by 
a  process  of  inversion,  while  other 
ferments  lead  to  precipitation  of 
the  casein  in  milk,  which  may 
again  undergo  resolution  in  the 
presence  of  other  members  of  the 
group.  Through  the  activity  of 
certain  of  these  enzymes  fermenta- 
tion, the  oxidation  of  carbohydrates,  etc.,  occur,  leading  to  the  formation 
of  alcohols,  organic  acids,  etc.^ 

Various  acids  ^  are  produced  by  the  specific  action  of  bacteria. 
Among  the  most  important  are  lactic,  acetic,  and  butyric  acids.  The 
Bacilhis  acidi  lactici  produces  lactic  acid  from  milk-sugar,  and  is  con- 
sidered the  usual  cause  of  acid  fermentation  in  milk. 

The  mycoderma  aceti  (Bacillus  aceticus)  in  the  presence  of  oxygen 
produces  acetic  acid  in  dilute  solutions  of  alcohol.  Butyric  acid  is 
produced  by  a  large  number  of  bacteria;  the  most  important  one, 
however,  is  the  Bacillus  butyricus,  an  anaerobic  organism. 

The  alkali'*  most  commonly  elaborated  by  bacteria  is  ammonia, 
which  is  a  final  product  of  proteid  dissolution:  e.  g.,  bacterial  disruption 
of  urea,  leading  to  the  formation  of  ammonia  and  carbon  dioxid. 

Putrefaction  of  animal  and  vegetable  bodies  is  brought  about  by 
a  great  variety  of  bacteria.  The  products  of  this  process  are  numerous, 
and  are  usually  divided  into  two  classes — the  volatile  and  the  nonvolatile. 

'  For  interesting  paper  on  the  possible  production  of  disease  by  enzymes 
independent  of  any  organism,  see  Moore,  "  Jour,  of  State  Medicine,"  Ap'ril,  1904. 

^  For  review  of  previous  work  and  original  observations  on  enzymes,  see 
Buxton,  "Amer.  Med.,"  July  25,  1903,  p.  137. 

^  See  Petruschky,  "  Centralbl.  f.  Bakt.,"  Bd.  vi;  1890,  Bd.  vii;  1896,  Bd. 
xix.      For  method  of  testing  reaction  see  chapter  on  Bacteriologic  Technic. 

^  See  Petruschky,  "  Centralbl.  f.  Bakt.,"  1889,  Bd.  vi:  1890,  Bd.  vii;  1896, 
Bd.  xix.      For  method  of  testing  reaction  see  chapter  on  Bacteriologic  Technic- 


Fig.  53. — B  a  c  i  l  l  u  s 

BUTYRICUS.      X 1000. 


4 

Fig.  54. — B  a  c  i  l  l  u  s 

ACIDI  I.ACTICI.    X  800. 


BACTERIA   AS  CAUSES  OF   DISEASE.  87 

The  malodorous  gases  belonging  to  the  former  group  are  lommonly 
the  product  of  anaerobic  bacteria.  Xovy  has  very  properly  con- 
sidered putrefaction  to  be  a  putrid  fermentation,  differing  from  other 
fermentative  processes  in  tlie  fact  that  the  bacteria  are  dealing,  in 
the  change  vmder  consideration,  with  proteid  matter,  and  only  to  a 
limitol  <ki^ree  with  sugars  and  starches. 

Ptomains  are  basic  substances  containing  nitrogen,  and  resemble 
in  chemic  constitution  such  vegetable  alkaloids  as  morphin  and  strych- 
nin. Like  the  vegetable  alkaloids,  in  combination  with  acids,  they 
form  definite  salts.  It  was  at  one  time  believed  that  bacteria  owed 
their  disease-producing  power  to  the  ptomains.  This  is  now  known 
not  to  be  the  case,  as  a  number  of  intensely  pathogenic  bacteria — for 
example,  the  diphtheria  bacillus — do  not  elaborate  ptomains. 

The  most  important  l)acterial  products,  so  far  as  at  present  known, 
are  the  toxins.  Toxins,  as  elaborated  by  the  pathogenic  bacteria,  re- 
semble to  a  varying  extent  the  albuminoid  poisons,  abrin  and  ricin, 
and  the  venom  of  serpents.  While  this  resemblance  is  possessed  to  a 
varying  degree  by  all,  each  toxin  is  the  specific  product  of  a  given 
microorganism.  Investigators  are  agreed  that  the  toxins  are  not  basic 
bodies  like  ptomains;  in  some  respects  they  resemble  globulins,  but 
their  proteid  nature  is  not  proved;  Roux  and  Yersin  thought  they 
might  be  enzymes.  As  a  matter  of  fact,  we  have  probably  never  seen 
a  pure  toxin,  know  next  to  nothing  of  their  ultimate  composition,  are 
unfamiliar  with  the  chemic  changes  which  evolve  them,  and  are  but  in- 
differently acquainted  with  their  action  in  the  production  of  disease. 

Toxins  are  unstable  compounds,  some  being  destroyed  by  compara- 
tively low  temperatures  (60°  to  80°  C),  and,  in  most  instances,  exposure 
to  sunlight  destroys  or  materially  alters  them.  They  are  the  most  active 
poisons  known:  it  is  estimated  that  Tji^  of  a  grain  of  the  pure  toxin  of 
tetanus  would  be  fatal  to  an  adult.  They  are  for  the  most  part  destroyed 
by  the  digestive  juices  of  the  body,  and  hence  are  innocuous  when  ad- 
ministered by  the  stomach.  Entering  the  circulation,  they  manifest 
their  poisonous  properties  upon  many  of  the  cells  of  the  body,  each 
toxin  apparently  selecting  certain  cellular  elements,  which  are  said  to 
show  an  unusual  degree  of  susceptibility.  It  is  not  improbable  that 
the  poison  directly  combines  with,  or  is  taken  up  by,  the  cells,  as  already 
mentioned  of  tetanus.     (See  p.  78.) 

Some  toxins  are  diffused  from  the  bacteria  into  the  culture  media 
in  which  they  are  found  in  the  largest  quantities  and  in  the  purest  state; 
these  are  called  extracellular  toxins  ;  conspicuous  among  the  organ- 
isms producing  this  typo  <>(  toxin  are  the  diphtheria  bacillus  anrl  the 
bacillus  of  tetanus.  Another  group  of  toxins  are  not  discharged  into 
the  culture  medium  by  the  growing  germ,  but  are  retainetl  in  the  ''n'tprial 
cell.     These  are  called  intracellular  toxins  ;    the  chief  poisons  ! 

by  the  typhoid  bacillus,  colon  bacillus,  the  Bacillus  enteritidis  ( ' 
the  dysentery  bacillus,  spirillum  of  cholera,  and  a  few  other  pathogenic 
organisms,  are  almost  exclusively  intracellular;   filtered  cultup'-    '•'  -'"  h 
organisms  are  but  feebly  toxic,  and  any  poison  that  they  con"  i 

easily  have  been  derived  from  the  protoplasm  of  dead  germs  ^i>  :;  ."uly 
present  in  such  cultures  as  the  result  of  bacteriolytic  processes.  The 
destruction  of  such  organisms  in  the  tissues  is  fraught  with  flanger  to 
the  economy  on  account  of  the  poisons  liberated  by  the  disintegration 


S8  GENERAL    PATHOLOGY. 

of  the  dead  bacterium.  In  this  connection  it  is  interesting  to  note  that 
a  number  of  nonpathogenic  organisms  contain  highly  toxic  intracellular 
poisons,  and,  therefore,  if  introduced  into  living  tissues  in  sufihcient 
quantity  and  destroyed  by  the  bacteriolytic  juices  and  cells  they  may 
liberate  sufficient  poison  to  cause  definite  tissue  alterations;  Vaughan 
has  proposed  for  this  type  of  organism  the  name  toxicogenic  bacteria, 
which  would  include  also  nonpathogenic  organisms  the  poisons  of  which 
are  extracellular.  In  the  case  of  bacteria  containing  intracellular  poi- 
sons it  is  evident  that  the  greater  the  bacteriolysis,  the  larger  the  amount 
of  poison  liberated  in  the  body,  and  it  is  not  improbable  that  in  some 
instances — for  example,  croupous  pneumonia — the  so-called  crisis  de- 
pends upon  the  rapid  destruction  of  bacteria  and  coincident  liberation 
of  intracellular  poisons  in  large  quantities.  Auclair^  states  that  the 
intracellular  poisons  are  usually  more  resistant  to  heat  and  very  much 
less  diffusible  in  the  tissues  than  the  extracellular  toxins.  In  common 
with  a  number  of  observers,  Auclair  has  shown  that  in  the  case  of  some 
organisms  these  intracellular  poisons  are  extremely  complex,  and  that 
by  the  use  of  different  solvents  toxic  substances  having  dissimilar  prop- 
erties may  be  extracted  from  the  bacterial  cell;  the  name  etherobacil- 
line,  xylolbacilline,  chloroformbacilline,  etc.,  has  been  given  to  such  ex- 
tracts derived  from  the  tubercle  bacillus.  For  the  intracellular  poisons 
of  bacteria  the  name  endotoxin  has  been  proposed.  As  will  be  seen 
later,  when  discussing  the  question  of  immunity,  the  extracellular  poi- 
sons are  antagonized  in  the  tissues  by  substances  called  antitoxins,  and 
the  intracellular  poisons  by  the  bacteriolytic  protective  agents. 

There  is  still  a  third  group  of  bacteria  in  which  the  elaborated  poisons 
are  both  intracellular  and  extracellular,  although  the  facts  at  present 
at  our  disposal  indicate  that  even  in  these  organisms  the  diffusible  toxic 
substances  are  unlike  the  more  firmly  anchored  intracellular  toxins. 
The  filtrate  from  the  unheated  cultures  of  the  tubercle  bacillus  contains 
definite  poisons;  if  the  culture  is  boiled  before  filtration,  the  toxicity 
of  the  fluid  is  increased,  indicating  that  some  of  the  intracellular  poisons 
are  extracted  by  the  hot  fluid;  the  bacilli,  however,  still  contain  a  quan- 
tity of  undissolved  poison,  as  can  readily  be  shown  by  further  extract- 
ing them  with  a  number  of  solvents  and  administering  to  animals  the 
substance  so  obtained. 

That  bacteria  produce  disease  almost  exclusively  through  the  activ- 
ity of  their  toxins  is  now  generally  admitted.  In  some  instances  the 
toxin  exerts  most  of  its  influence  directly  at  its  point  of  production. 
According  to  Auclair,  the  toxins  of  the  actinomyces,  gonococcus,  and 
tubercle  bacillus  act  locally;  the  typhoid  bacillus,  streptococcus,  and 
staphylococcus  poisons  manifest  both  local  and  general  action.  It 
is  well  known  that  the  tetanus  toxin  exerts  no  important  local 
influence,  but  manifests  its  poisonous  quality  almost,  if  not  quite, 
exclusively  by  way  of  the  nervous  system.  The  poisons  produced 
by  the  diphtheria  bacillus  are  responsible  for  some  of  the  impor- 
tant local  changes,  but  the  intense  systemic  action  of  the  toxin  is 
indicated  by  the  wide-spread  lesions  of  diphtheria,  such  as  destruc- 
tion of  cells  in  the  liver,  degeneration  of  nerves,  changes  in  the 
myocardium,  irritation  and  inflammation  of  the  kidney,  etc.; 
^  "Arch,  de  Med.  Exper.  et  Anat.  Path.,"  Nov.,  1903.  p.  725. 


BACTERIA   AS  CAUSES  OK   DISKASK.  Sg 

Welch'  and  IHexner  have  demonstrated  that,  in  adthtion  to  its  solu- 
ble toxin,  the  diphtheria  bacillus  possesses  an  intraiellular  ]>oison 
concerned  in  the  pnjduction  of  false  membrane.  The  increase  in  the 
leukoc>'tes  seen  in  a  number  of  infections  is  clearly  attributable  to  the 
action  of  the  toxins  on  leukocyte-forming  tissues.  That  such  struc- 
tures are  influenced  in  infection  is  shown  most  clearly  by  the  studies  of 
Muir-  and  Longcope.^  Burton-Sanderson*  has  crystallized  our  previous 
knowledge  of  toxin,  particularly  calling  attention  to  the  fact  that 
while  it  is  necessary  to  recognize  the  deleterious  influence  of  bacterial 
])oison,  it  is  equally  important  to  appreciate  that  almost  exclusively 
through  this  influence  the  tissues  of  the  body  are  stimulated  to  the 
production  of  antagonizing  agents  (antibodies,  see  Immunity),  through 
the  intervention  of  which  bacterial  action  is  arrested. 

The  ultimate  fate  of  bacterial  poisons  is  not  known;  when  neutral- 
ized or  destroyed  by  the  body-cells  or  fluids,  or  in  any  way  rendered 
harmless,  they  may  he  excreted  by  the  emunctories. 

Subinfection. — As  already  stated  when  considering  7Joisons.  it  is  a 
well-known  fact  that  small, frequently  repeated  doses  of  such  toxic  agents 
as  lead. arsenic,  mercury, etc., give  rise  tospecial  forms  of  chronic  intoxica- 
tion characterized  in  each  instance  by  a  fairly  definite  clinical  picture  and 
more  or  less  constant  lesions.  A  number  of  observers'"  have  conceived 
the  idea  that  in  one  way  or  another  small  quantities  of  l)acterial  toxins, 
constantlv  entering,  or  continuously  produced  in  the  system,  may  give 
rise  to  slowly  progressing  lesions  without  at  any  time  the  manifesta- 
tions of  frank  infection.  For  this  condition  Adami  suggested  the  name 
subinfection.  It  is  not  impossible  that  profound  anemias  and  marked 
structural  alterations  in  organs  may  in  this  way  be  brought  about." 

The  growth  of  one  germ  may  develop  conditions  favorable  for  the 
pullulation  or  pathogenic  action  of  another, — a  condition  called  sym- 
biosis. The  presence  of  oxygen-absorl)ing  bacteria  may  assist  in  secur- 
ing the  necessary  anaerobic  medium  for  the  bacillus  of  tetanus,  and  alco- 
hol-splitting organisms  may  keep  that  sul)Stance  sufficiently  low  to 
permit  continuous  growth  of  any  associated  yeasts.  It  is  certain  that 
in  the  presence  of  pathogenic  organisms  which  destroy  tissue,  oppor- 
tunitv  for  the  growth  of  saprophytic  bacteria  is  afforded  and  the  chnical 
and  pathologic  features  of  infection  intensified.  It  is  not  established, 
however,  that  the  organisms  of  decomposition  in  any  material  way  facili- 
tate the  action  of  the  disease-producing  germs.  Recent  studies  in  the 
proliferation  of  unicellular  animal  parasites  indicate  that  at  least  some 

'•  Brit.  Med.  Jour..'"  Oct.  ii.  iqo2,  iios:    "' Lancet."  Oct.  ii,   1902.  p.  077; 
•  Medical  News,"  Oct.  iS,  1902,  p.  721  ;   "  Science."  Nov.  21  and  2S.  i«,o2;   ••  Post- 
graduate." Dec,  igo2.  p.  1416:   "  Huxley  Lecture." 

'  ■■  Trans.  Path.  Soc.  of  London."  1902,  vol.  53.  p.  370.  ,.        •     ,       . 

'  ••  Bulletin  of  the  Aver  Clinical  Laboratory  of  the   Pcnna.   Hospital 
Ian..  1 90s.  /•,... 

••■Lancet."  Xovemher  i.  1902:     'Trans.  Path.  Soc.  of   London.      1 

*  This  matter  has  been  particularly  investigated  by  .\dami  and  his 
Charlton  (•  lour,  of  Medical  Research."  vol.  viii,  p.  344.  Novembt-r.  iqo 
some  interesting  experiments  upon   the  i)roduction  of  anemia  by  repe.n 'i   .ii- 
ministration  of  sublethal  doses  of  the  colon  bacillus  and  gives  bibliography  which 
will  start  the  inquirer  on  the  track  of  j,r  •  •   ••    '"..-rature. 

"  The  local  action  of  bacteria  is  <li-  h  each  organi.sm: 

ti<m.  Tuberculosis.  DiTihthiria    .\rtin    •  tc   . 


90  GENERAL    PATHOLOGY. 

of  them   require   the   presence   of   a   vegetable   organism   through   the 
energ}'  of  which  food  for  the  protozoon  is  made  available. 

Pure  or  simple  infections  are  probably  less  common  than  mixed  or 
concurrent  infections.  The  latter  may,  by  adding  one  toxin  to  another, 
further  embarrass  tissue  resistance  and  intensify  systemic  poisoning; 
this  is  notably  the  case  in  many  conditions.  Whatever  may  be  the 
cause  of  scarlet  fever,  its  lesions  are  greatly  intensified  by  the  coincident 
streptococcus  infection  of  the  throat;  the  same  is  true  of  the  influence 
exerted  by  the  pus-producing  organisms  in  the  pocks  of  variola.  When 
pyogenic  bacteria  invade  tuberculous  tissue,  local  disintegration  and 
systemic  intoxication  are  both  increased.  On  the  other  hand,  facts 
are  not  wanting  to  show  that  one  germ  may  antagonize  the  action  of 
another;  the  virulence  of  anthrax  bacilli  is  modified  in  cultures  con- 
taining the  bacillus  pyocyaneus. 

PATHS  OF  INFECTION. 

Bacteria  enter  the  tissues  in  a  number  of  ways.  The  fact  that 
many  organisms  capable  of  producing  disease  are  constantly  present  on 
the  surface  of  the  body,  within  the  alimentary  canal  and  elsewhere,  estab- 
lishes that  the  various  surfaces,  both  external  and  internal,  constitute 
protective  barriers  the  efficiency  of  which  necessarily  varies.  The  fol- 
lowing are  the  principal  paths  through  which  infections  occur: 

Transplacental  infection  has  been  shown  to  be  possible  in  anthrax, 
pneumonia,  typhoid,  pyogenic  infections  in  which  the  germs  are  pres- 
ent in  the  maternal  circulation,  recurrent  fever,  smallpox,  glanders,  tuber- 
culosis, and  syphihs.  Wassermann^  has  collected  12  cases  in  which 
tubercle  bacilli  traversed  the  placenta.  There  are  numerous  recorded 
instances  in  which  anthrax,  both  natural  and  experimental,  has  passed 
from  mother  to  fetus.  Konradi^  concludes  that  it  is  possible  for  the 
virus  of  rabies  to  traverse  the  placenta.  Infection  across  the  placenta 
is  possible  only  when  the  organism  is  present  in  the  maternal  blood.  It 
is  probable,  although  not  demonstrated  in  all  instances,  that  the  placenta 
itself  must  be  affected  in  order  to  permit  infectious  material  to  enter  the 
fetal  circulation.  It  is  well  known  that  antibodies  in  the  maternal  blood 
may  reach  the  fetus;  it  is  not  estabhshed,  however,  that  bacteria  mav 
pass  from  the  mother  to  the  fetus  without  structural  changes  in  the 
placenta.  Syphihs  is  the  only  disease  in  which  we  have  reason  to  be- 
lieve that  the  fetus  may  deleteriously  influence  the  maternal  tissues, 
themselves  previously  sound ;  even  here  the  possibility  is  not  univer- 
sally admitted.  That  the  syphilitic  fetus  exerts  some  action  on  the 
maternal  organs  is  indicated  by  the  fact  that  it  may  nurse  from  the 
mother  without  danger  of  infecting  her,  but  can  infect  a  wet-nurse. 

Infection  through  the  skin  ^  rarely  occurs  provided  the  epithelium 
is  intact.  Cutaneous  and  subcutaneous  abscesses  have  been  produced 
by  rubbing  pus-producing  cocci  into  the  skin;  the  experiment,  however, 
is  not  always  successful,  and  the  fact  that  these  organisms  are  constantly 
present   on   the   surface   of   the   body   without   producing   suppurative 

*  ■'  Handbuch  der  Mikroorganismen,"  Bd.  i,  p.  39:;. 
^  "  Centralbl.  f.  Bakt.,"  Jan.  25,  1905,  p.  60. 

^  For  article  on  the  defensive  powers  of  the  normal  skin  see  paper  by  Sa- 
bouratid,  "Bull,  do  I'lnst.  Pasteur,"  1904,  vol.  ii.  p.  233. 


BACTERIA   AS  CAUSES  OF   DISEASE.  gi 

lesions  shows  tonclusively  epithelial  protection,  in  a  number  of  in- 
stances I  have  observed  in  myself  and  in  my  assistants  suppurative 
lesions  clearly  l»eginning  m  the  hair  follicles  of  the  forearm,  and  it 
is  not  improbable  that  the  appendages  of  the  skin  (hair  follicles,  seba- 
ceous and  sweat  ducts)  afford  points  for  the  deposit  of  bacteria,  which, 
under  favorable  circumstances,  may  penetrate  the  tissues.  Many 
facts  go  to  show  that  skin  of  different  parts  of  the  body  possesses  dif- 
ferent degrees  of  protection;  the  more  highly  keratinized  layers  of  the 
])alms  of  the  hands  and  soles  of  the  feet  must  necessarilv  be  difficult  to 
penetrate.  Ordinarily  transcutaneous  infection  occurs  through  wounds 
or  abrasions  which  may  be  microscopic  and  need  not  penetrate  the 
corium.  The  diphtheria  bacillus,  the  streptococcus  of  erysipelas,  and 
even  the  tubercle  bacillus  have  been  known  to  infect  Ijlistered  surfaces. 

Infection  through  the  alimentary  canal  undoubtedly  represents  the 
most  frequent  method  by  which  bacteria  enter  the  body,  but  even  Ity 
this  route  the  surface  protection  in  certain  parts  is  relatively  high;  the 
thick  epithelial  layers  upon  the  buccal  mucosa,  tongue,  and  esophagus 
offer  much  greater  protection  than  the  more  thinly  clad  intestine.  The 
latter  structure  is  afforded  a  certain  amount  of  protection  by  the  bac- 
tericidal activity  of  the  gastric  juice;  it  has  repeatedlv  been  shown 
that  gastric  secretion  is  destructive  to  cholera  organisms,  and  that 
during  epidemics  of  cholera  gastric  indigestion  favors  the  occurrence 
of  infection.  Abrasions  about  the  mouth,  particularly  of  the  lips  and 
along  the  gingival  margin,  may  permit  the  ingress  of  pathogenic  bacteria. 
It  is  possible  for  infection  to  occur  through  carious  teeth.  Tonsillar 
infection  has,  within  recent  years,  been  shown  to  be  of  frequent  oc- 
currence. Jonathan  Wright '  holds  that  the  tonsillar  crypts  are  test 
tubes  in  which  bacterial  cultures  are  constantly  opposed  by  the  resist- 
ing power  of  the  tissues.  Lacunar  and  ragged  tonsils,  and  tonsils 
with  plugged  crypts,  are  particularly  favorable  for  the  entrance  of  bac- 
teria. Streptococci,  staphylococci,  and  tubercle  bacilli  have  been 
demonstrated  in  the  tonsillar  tissue,  the  last  without  the  histologic 
changes  of  tuberculosis.  It  is  generally  conceded  that  tulierculosis  of 
the  cervical  lymph-nodes  is  usually  due  to  infection  through  the  tonsils. 
The  depressions  and  crypts  in  these  organs  afford  points  in  which  bac- 
teria may  secure  a  certain  degree  of  protection;  after  recovery  from 
diphtheria  (tonsillar  and  pharyngeal)  the  bacillus  sometimes  remains 
for  weeks  on  the  roughened  surfaces  of  the  tonsils.  The  pharynx  as  a 
point  for  bacterial  entrance  occupies  a  position  of  less  importance  than 
the  tonsils.  Infection  through  the  esophageal  mucosa  is  very  rare. 
It  has  been  demonstrated  by  a  number  of  observers  that  bacteria  can 
pass  through  an  intestinal  mucosa  which,  so  far  as  can  be  determined, 
is  intact.  Ford,-  Morgan,^  Xicholls.^  and  Wrzosek^  have  shown 
that  bacteria  are  not  infrequently  present  in  normal  tissues,  and  Xich- 
olls'  studies  of  the  mesentery  indicate  that  germs  may  enter  through 
the  intestine.  Typhoid  infection  is  practically  always  by  this  route. 
Cholera  organisms  proliferate  in  the  cavity  of  the  intestine  and  from 

'  '■  Medical  Xcws,"  March  4,  1905,  p.  385. 

'  "  Jour,  of  Hygiene,"  iqoi,  vol.  i,  p.  277. 

^  ■■  Lancet."  July  2,  1904,  p.  21. 

*    ■  Jrair.  of  Med.  Research."  May.  1904.  p.  445. 

^  "■"Virrhr.w's  Arch  ."  h<]    i->    i'.  S-v 


92  GENERAL    PATHOLOGY. 

this  point  disseminate  their  toxic  influences  throughout  the  system  without 
giving  rise  to  any  characteristic  local  lesion.  Bacteria  from  the  intestine 
may  infect  the  biliary  and  pancreatic  canals  by  continuity,  or,  passing 
through  the  intestinal  wall,  may  reach  the  portal  circulation,  lymph- 
glands  of  the  mesentery,  or,  by  way  of  the  chyle  vessels  and  thoracic 
duct,  indirectly  enter  the  circulation.  It  is  generally  conceded  that, 
in  practical])-  all  cases,  infections  of  the  appendix  are  from  the  intestine. 

Infection  through  the  air-passages.  The  normal  mucosa  of  the  nose 
and  its  accessory  sinuses  usually  destroys  the  bacteria  coming  in  con- 
tact with  it.  Once  infected,  however,  extension  may  occur  to  sinuses, 
middle  ear,  and  even  the  brain.  The  meningococcus  has  been  demon- 
strated in  the  nasal  mucosa  before  and  during  an  attack  of  meningitis, 
and  Maragliano  ^  has  produced  the  disease  by  spraying  the  nose  of 
rabbits  with  cultures  of  the  organism.  Bacteria  may  infect  the  bron- 
chial mucosa  or,  passing  through  this  structure,  may  reach  the  peri- 
bronchial lymphatics  and  adjacent  glands.  In  a  similar  way  the  pul- 
monary parenchyma  and  pleura  may  become  infected.  Recent  studies 
tend  to  minimize  the  frequency  with  which  pulmonary  tuberculosis 
is  due  to  inhalation  and  direct  infection  of  the  lung  tissue;  by  contact 
with  the  mucosa  of  the  upper  air-passages  and  bronchial  tubes  the 
bacterial  content  of  the  air  reaching  the  alveoli  is  reduced  to  a  minimum. 

Infection  through  the  genitourinary  system.  In  certain  diseases 
(gonorrhea)  infection  of  the  meatus  and  the  urethra  constitutes  the 
ordinary  path  of  entrance.  In  the  male,  infection  may  traverse  the 
seminal  tract  and  reach  the  testes,  from  which,  or  from  some  inter- 
mediate point,  the  blood  may  be  invaded.  In  the  female  urethral 
infection  and  consequent  cystitis  are  less  constant,  but  when  the  bladder 
in  either  sex  becomes  involved  an  ascending  infection  may  traverse 
the  ureters  and  renal  pelvis,  finally  attacking  the  kidney.  In  the  fe- 
male the  birth  canal  offers  a  particularly  favorable  field  for  the  growth 
of  bacteria,  and  when  subjected  to  trauma  or  in  other  ways  injured 
may  constitute  an  important  center  from  which  dissemination  may 
occur.  Gonorrhea  in  the  female  attacks  the  vulva,  vulvovaginal  glands, 
vagina,  cervix,  endometrium,  and  Fallopian  tubes;  occasionally  in- 
fection may  extend  to  the  peritoneum,  and,  from  any  of  the  points 
named,  the  gonococcus  occasionally  enters  the  circulation.  In  the 
injuries  incident  to  child-birth  abrasions  and  lacerations  in  the  birth 
canal  open  the  submucosa  through  which  both  local  and  general  in- 
fections may  occur. 

PATHS  OF  EXTENSION. 

Once  infection  has  reached  the  connective  tissues  by  anv  of  the 
routes  indicated  it  may  be  restricted  to  a  local  lesion,  may  be  propagated 
by  continuity  or  by  contiguity  to  adjacent  structures,  may  extend  or  be 
carried  by  the  lymph-stream  or  invade  the  lymphatics  as  a  continuous 
infection,  or,  reaching  the  circulation  by  any  path,  the  organism  may 
be  carried  and  distributed  with  the  blood.  With  regard  to  Ivmphatic 
extension  particular  attention  should  be  called  to  the  influence  of  Ivmph- 
nodes  in  limiting  the  spread  of  bacteria.  Histologically  these  structures 
possess   an    architecture   eminently   adapted   to   the   filtering   function 

'  "  Gaz.  Osped.  et  Clin.,"  1Q05,  Xo.  19. 


HACTKklA    AS   CAl'SHS   OV   DISKASK.  93 

whicli  they  clearly  manifest.  Any  infeetion  liavinj.,'  a  tendency  to  ex- 
tend by  the  ]ym|)h  paths  is  commonly  shown  hy  enlargement  of  the 
glands  through  which  the  lymi)h  of  the  area  drains;  thus  in  syphilis, 
gonorrhea,  chancroiil,  and  other  infections  of  the  genitalia  the  inguinal 
nodes  enlarge.  The  point  of  infection  in  bubonic  |)lague  may  be  shown 
by  the  first  set  of  glands  infected,  infections  of  the  intestine  cause  en- 
largement of  the  mesenteric  glands,  and  infections  through  the  mouth 
and  pharynx  commonly  give  rise  to  swelling  in  the  anterior  cervical 
glands.  The  lymjih  has  been  shown  to  possess  certain  antitoxic  and 
Ijactericidal  '  (jualities,  and  the  fact  that  tuberculosis  may  be  restricted 
to  a  certain  node  or  group  of  nodes  clearly  indicates  the  inhibiting 
influence  which  these  structures  exert. - 

By  whatever  route  the  microorganism  enters  the  tissues,  it  is  met 
by  inhibiting  influences  with  which  it  must  contend  for  supremacy.  The 
external  barriers  are  of  value,  but  clearly  of  inferior  imjjortance  when 
compared  with  powerful  antibacterial  properties  {)Ossessed  l)V  the  bodv- 
fluids  and  somatic  cells.  A  proper  estimate  of  these  qualities  is  of  the 
highest  interest,  and  this  leads  to  a  consideration  of  the  forms  of  immu- 
nity. 

'  Meltzcr  and  Norris.  ""  Jour,  of  Exp.  Med.."  vol.  ii.  No.  6. 
-  Manfrcdi.  "  Virchow  Arch.."  1899,  Bd.  civ.  j).  ^^5. 


CHAPTER  IV. 
BACTERIA  AS  CAUSES  OF  DISEASE.— (Continued.) 

IMMUNITY.! 

It  has  long  been  a  recognized  fact  that  a  person  having  suffered  from 
an  attack  of  certain  infectious  diseases  is  more  or  less  refractory  to  sub- 
sequent infection  by  the  specific  organism  of  that  disease.  This  insus- 
ceptibility differs  in  different  affections  and  is  not  the  same  in  all  persons. 
Some  of  the  eruptive  diseases,  of  which  but  one  attack  is  ever  expected, 
may  occur  in  the  same  individual  more  than  once ;  Mycelius-  has  collected 
514  cases  of  smallpox,  ^t,  of  scarlet  fever,  37  of  measles,  and  208  of 
typhoid  in  which  the  patients  had  from  two  to  four  attacks. 

A  number  of  forms  of  immunity  are  now  recognized.  In  the  first 
place,  it  is  to  be  remembered  that  an  absolute  immunity  to  infection 
rarely,  if  ever,  exists.  As  a  rule,  the  highest  attainable  immunity  may 
be  broken  down,  and  an  animal  naturally  possessing  extraordinary 
resistance  to  some  particular  form  of  infection  may  be  made  suscep- 
tible. Thus,  the  chicken,  which  is  naturally  immune  to  anthrax, 
may  be  made  siisceptible  by  more  or  less  prolonged  immersion  in  cold 
water.  In  a  similar  way  susceptibility  may  be  increased  by  starva- 
tion, improper  food,  fatigue,  shock,  hemorrhage,  and  associated  or 
concurrent  infections.  The  influence  of  the  last-named  condition  in 
breaking  down  a  more  or  less  natural  barrier  to  infection  is  shown  by 
the  rapidity  with  which  individuals  occasionally  succumb  to  tubercu- 
losis of  the  lungs  consecutive  to  other  infectious  processes  in  those 
organs.  The  catarrhal  pneumonia  incident  to  measles  and  influenza 
may  afford  a  suitable  nidus  for  the  lodgment  of  the  tubercle  bacillus; 
the  inflammatory  changes  induced  by  the  presence  of  foreign  bodies 
in  the  lung  may  act  as  an  etiologic  factor  in  the  induction  of  septic  pneu- 
monia. The  influence  of  dose  on  the  occurrence  of  infection  further 
illustrates  the  relationship  between  an  absolute  resistance  and  an  im- 

^  The  literature  of  immunity  is  widely  distributed,  partictilarly  in  German, 
French,  Italian,  and  English  publications.  Aschoff,  "  Seitenkettentheorie  u. 
ihre  Anwendung  auf  die  Kunstlichen  Immunisierungsprozesse,"  1902;  extensive 
bibliography.  Ritchie,  "Jour,  of  Hygiene,"  vol.  i,  1902,  pp.  215,  251,  452,  with 
references  to  106  articles.  Rosenau,  "Hygienic  Laboratory  Bulletin  No.  21," 
1905,  full  bibliography.  Welch,  "Brit.  Med.  Jour.,"  Oct.  11,  1902,  Huxley  Lec- 
ture on  Recent  Studies  on  Immunity.  Ernst,  "Theories  of  Bacterial  Immu- 
nity," 1903.  Discussion  on  Immunity,  Brit.  Med.  Assoc,  1904,  published  in 
"Brit.  Med.  Jour.,"  Sept.  10,  1904,  p.  557;  Bulloch's  discussion  gives  references 
to  107  articles.  Recent  summary  of  Ehrlich's  studies  will  be  found  in  the  "  Ge- 
sainmelte  Arbeiten  zur  Immunitatsforschung,"  1904.  A  good  review  of  the  sub- 
ject is  now  being  published  in  the  "Jour.  Amcr.  Med.  Assoc,"  having  begun  in  the 
number  for  January  28,  1905,  but  not  as  j-et  completed.  An  excellent  summary 
will  be  found  in  Bolduan's  translation  of  Wassermann's  monograph  on  "  Immune 
Sera,  Hasmolysins,  Cytotoxins  and  Precipitins,"  1904.  See  also  Nuttall,  "Blood 
Immunity  and  Blood  Relationship,"  1904. 

^  Quoted  by  McCaskey,  "Amer.  Jour,  of  the  Med.  Sci.,"  July,  1902. 

94 


HACTKkIA    AS   CAUSHS  (JK    DISEASK.  95 

nuinity  of  moderate  <legree.  Huxton  '  has  shown  that  i  ccm.  of  fresh 
normal  rabbit's  scrum  may  Ite  expected  to  kill  1,000,000  typlioid  bacilli, 
50,000,000  paratyphoid  organisms,  and  100,000,000  cholera  spirilla. 
Large  doses  bring  about  fatal  results,  while  smaller  doses,  even  when 
repeated,  may  only  strengthen  the  resistance  of  the  animal.  The  facts 
adduced  go  to  show  that  there  is  first  an  immunity  that  approaches 
an  absolute  resistance  to  the  disease,  and,  second,  there  is  a  high  degree 
of  susceptibility,  which  may  be  so  marked  that  the  smallest  possible 
dose  of  an  infectious  agent  will  prove  fatal  to  the  animal  in  fiuestion. 
Between  these  two  extremes  all  possible  intermediate  forms  of  reaction 
to  infection  may  exist.  An  attempt  has  been  made  to  subdivide  these 
intermediate  gradations  of  immunity  and  susce|)tibility  into  an  absolute 
immunity  and  a  partial  immunity.  Such  a  division  is  not,  in  the  pres- 
ent state  of  our  knowledge,  possil)le. 

Natural  immunity  is  the  resistance  to  some  particular  form  of  infec- 
tion transnntted  from  parent  to  offspring.  This  form  of  immunitv  mav 
belong  to  some  particular  species  in  the  animal  kingdom  or  to  but  one 
race  of  animals.  As  examples  of  this  condition  may  l)e  noted  the  sus- 
ceptibility of  the  field  mouse  and  the  immunity  of  the  white  mouse  to 
glanders;  the  relative  immunity  of  the  negro  to  yellow  fever  and  ma- 
laria and  the  great  susceptil)ility  of  the  white  race. 

When  an  animal  naturally  susceptible  to  a  disease  develo])S  immu- 
nity, the  condition  is  known  as  acquired  immunity  ;  this  may  be  further 
subdivided  into  active  and  passive  immunity. 

Active  immunity  may  be  brought  about  in  a  number  of  ways.  An 
individual  having  suffered  from  an  attack  of  one  of  the  infectious  dis- 
eases, such  as  smallpox,  becomes  immune  to  subsequent  attacks;  the 
intensity  and  duration  of  this  immunity  will  vary  with  different  diseases 
and  different  individuals.  Thus,  in  smallpox  immunity  is  almost  abso- 
lute; on  the  other  hand,  with  cholera,  and  jjarticularly  with  erysijjelas, 
the  duration  of  the  period  is  short  and  the  degree  of  immunity  never 
very  great.  In  ervsipelas  some  practitioners  l)elieve  that  one  attack 
predisposes  to  a  second,  thus  indicating  that  instead  of  immunity  there 
may  be  increased  susceptibility. 

Acquired  immunity  may  also  be  brought  about  by  inoculation. 
The  inoculation  may  be  made  with  attenuated  microorganisms,  or 
with  such  small  doses  of  virulent  bacteria  that  the  disease  is  not  induced ; 
by  gradually  increasing  the  dose  the  animal  becomes  resistant  to  a 
quantity  of  the  infectious  agent  that  at  first  would  have  proved  rapidly 
fatal.  As  examj)les  of  immunity  induced  by  inoculation  with  attenuatcil 
organisms,  the  protection  afforded  to  sheej)  by  inoculation  with  anthrax 
bacilli,  made  less  virulent  by  cultivation  at  high  temi)eratures,  may 
be  cited.  Although  at  present  we  are  not  certain  what  organisms  — 
vegetable  or  animal — are  active  in  cowpox,  vaccinia,  or  smallpox,  we 
are  probably  justified  in  believing  that  vaccination  induces  afonnof  im- 
munity properly  classified  here. 

It  appears  to  have  been  demonstrated  that  the  tubercle  bacillus 
normally  producing  tuberculosis  in  cattle  is  most  virulent  for  those 
animalSi  the  bacillus  producing  tulierculosis  in  chickens  most  virulent 
for  chickens,  and  the  same  rule  applies  to  the  bacilli  causing  tuberculosis 
in  cold-blooded  animals.  Recent  experiments  seem  to  indicate  that  it 
'  "  Tour,  of  Med.  Research."  vol.  xiii.  p.  ^05. 


96  GENERAL    PATHOLOGY. 

may  be  possible  to  immunize  one  species  by  the  use  of  tubercle  bacilli 
highly  virulent  for  another  but  less  so  for  the  zoologic  group  experi- 
mented upon;  working  along  this  line,  Pearson  and  Gilliland  have  suc- 
ceeded in  producing  a  certain  degree  of  immunity  in  bovines  by  the  use 
of  tubercle  bacilli  of  human  origin. 

Again,  immunity  may  be  secured  by  the  use  of  bacterial  products 
without  using  the  living  organisms  themselves.  The  substances 
utilized  for  this  purpose  may  be  filtered  toxins,  derived  from  actively 
growing  virulent  organisms,  or  the  cultures  may  be  sterilized  at  tem- 
peratures (55°  to  65°  C.)  so  low  that  the  toxins  and  proteid  constituents 
of  the  bacterial  cell  are  not  destroyed  and  the  sterile  fluid  may  be  in- 
jected subcutaneouslv  or  intraperitoneally.  Haffkine's  method  of 
immunizing  against  plague  consists  in  the  subcutaneous  injection  of 
I  to  3  c.c.  of  a  bouillon  culture  of  the  bacillus  killed  by  exposure  to 
70°  C.  for  one  hour.  Wright's  antityphoid  inoculations  consist  of  i  c.c. 
of  a  heat-killed  bouillon  culture  of  the  bacilli.  Immunization  against, 
and  treatment  of,  tuberculosis  by  chemical  products  of  tubercle  bacilli 
(tuberculosis),  while  not  fulfilling  expectations,  has  yielded  in  some 
instances  promising  results.^  The  use  of  a  sterile  filtrate  for  inducing 
immunity  is  the  method  at  present  in  vogue  for  immunizing  animals 
in  the  preparation  of  diphtheria  antitoxin.^  A  certain  degree  of  immu- 
nity may  be  induced  by  feeding  animals  on  bacterial  products,  or  even 
the  bacteria  themselves.  Lofifler^  has  recently  shown  that  desiccated 
bacteria  subjected  to  dry  heat  at  150°  C.  are  eminently  adapted  to  im- 
munization; he  has  also  used  similarly  prepared  serum.  The  fact  that 
dry  enzymes  withstand  relatively  high  temperatures  suggested  to  Lof- 
fier  the  plan  which  he  has  followed  wath  success. 

It  has  been  proposed  to  utilize  the  terms  induced,  artificial,  or  ex- 
perimental immunity  to  cover  immunity  brought  about  by  experiment 
or  inoculation,  and  to  limit  the  term  acquired  immunity  to  the  immunity 
that  follows  an  attack  of  disease. 

Passive  Im.m.unity, — If  an  animal  that  has  been  rendered  immune 
bv  some  of  the  methods  previouslv  given  be  bled,  and  the  blood,  or 
the  serum  separated  from  the  blood,  injected  into  another  animal  not 
previouslv  immunized,  the  second  animal  acquires  a  more  or  less  tem- 
porary immunitv,  which  has  been  designated — by  reason  of  its  temporary- 
character — passive  immunity. 

The  immunity  of  this  animal  is  dependent  upon  the  presence  of  anti- 
substances  taken  from  an  actively  immune  animal.  These  substances 
disappear  with  a  rapiditv  that  varies  in  dififerent  animals,  and  with 
immunity  against  different  infections.  The  induction  of  this  form 
of  immunity  becomes  important  because  of  our  ability  to  utilize  it 
in  the  prevention  and  treatment  of  disease.  Thus,  if  a  number  of 
children  be  exposed  to  diphtheria,  a  temporary  immunity  in  their 
bodies  may  be  brought  about  by  injecting  into  their  tissues  a  sufficient 
quantity   of  immunizing  serum.     This  renders  them  immune   for  the 

*  The  literature  of  this  subject  can  be  traced  from  references  given  by  Tru- 
deau  and  Baldwin,  "Amer.  Jour,  of  the  Med.  Sci.,"  December.  1898.  and  January. 
1899;  see  also  "Report  of  the  Henry  Phipps  Instittite  for  the  Study,  Preven- 
tion and  Treatment  of  Tuberculosis."  vol.  i.  1904. 

^  See  chapter  on  Bacteriologic  Technic. 

'•'  "  Deutsche  med.  Woch."  Dec.  22.  1904. 


HACTKKIA    AS   CAl'SKS   Ol-    DISIC  ASK.  <)7 

time  being,  and  i1r'\  (.'srajic  nitoition  troin  a  snij^k'  cxiiosvirt'.  Aj^jain, 
tliis  kind  of  immunity  forms  a  l)asis  for  the  treatment  of  the  fliseasc 
already  developed.  As  it  is  well  known  that  tissues  arc  damaged  by 
toxins  of  bacteria,  any  agent  having  a  tendency  to  prevent  this  action 
becomes  etlicacious  in  the  treatment  of  the  disease:  hence,  knowing 
that  a  child  is  already  infected  by  the  di{jhthcria  bacillus,  the  toxms 
being  ])roduced  may  be  neutralised  by  introducing  into  the  cinulation 
of  the  patient  a  sutHcicnt  quantity  of  the  antitoxm  removed  from  an 
animal  that  has  been  actively  immunized.  Upon  this  basis  rests  the 
present  serum  therapy  of  diphtheria  and  related  infections. 

Local  Immunity. —  It  has  been  shown  that  if  the  ear  of  a  rabbit  has 
been  inoculated  with  the  streptococcus  of  erysipelas  anfi  the  animal 
has  recovered,  a  subsequent  inoculation,  made  simultaneously  upon 
!)Oth  ears,  will  be  followed  by  a  more  active  inflammation  in  the  ear 
that  has  not  been  previously  inoculated.  It  is  also  known  that  granu- 
lation tissue  is  more  resistant  to  the  inroads  of  infection  than  the  normal 
tissue  of  the  part  involved.  Both  these  facts  indicate  the  presence  of  a 
resistance  more  or  less  restricted  to  limited  areas.  Whether  this  resist  ance 
is  due  to  the  presence  of  inflammatory  products  or  to  some  {)eculiar 
anti-bodvnot  diffused  by  the  circulating  fluids  has  not  been  determined. 

A  careful  studv  of  the  problems  m  immunity  shows  that  for  the 
successful  prevention  or  cure  of  bacterial  diseases  it  is  necessary  tf) 
recognize  two  distinct  groups,  which,  however,  undoubtedly  overlaj) 
each  other.  In  one  of  these  the  dominant  symptoms  and  lesions  arc 
due  to  the  toxic  action  of  extracellular  ])oisons;  this  is  especially  true 
of  diphtheria  and  tetanus.  In  diseases  belonging  to  this  class  the  im- 
munity depends  upon  neutralizing  the  extracellular  toxins  and  need 
not  be  si)eciflcally  directed  toward  destruction  of  the  organism.  In 
this  class  protection  depends  upon  what  has  been  called  antitoxic  im- 
munity. In  a  second  group  of  diseases  the  extracellular  toxins  arc 
of  far  less  importance  than  those  poisons  which  develop  and  are  re- 
tained, during  the  life  of  a  germ,  within  the  protoplasm  of  the  bacterial 
cell,  in  diseases  due  to  bacteria  belonging  to  this  class  (typhoid, 
cholera,  etc.)  destruction  of  the  germ  or  at  least  neutralization  of 
the  endotoxin  is  necessary  to  accomplish  the  desired  result.  The  an- 
tagonism is  directed  toward  the  bacterial  cell;  the  germ  must  be  ]>rv- 
vented  from  multiplying,  and  in  order  to  accomplish  this  a  bacterio- 
lytic immunity  is  neccssarv. 

Theories  of  Immunity.'— As  far  back  as  the  early  years  of  the  eigh- 
teenth centurv  it  was  known  in  Europe  that  the  Turks  inoculated  their 
children  with 'smallpox  matter,  in  the  hope  of  bringing  on  a  mild  attack 
of  the  disease  and  therebv  inducing  an  immunity.  To  Lady  Marv 
Wortley  Montague  belongs'  the  honor  of  first  calling  serious  attention 
to  this' practiced  in  a  letter  addressed  to  her  friends  in  Englanfl.  and 
dated  March  23,  1 718.  In  this  letter  is  described  the  inoculation  of 
her  voung  son  with  smallpox  matter.  Jenner's  remarkable  discovery 
of  tlie  immunitv  conferred  by  the  cow-pox  virus  shortly  followed.  The 
more  deflnite  knowledge  of  the  causes  of  disea.se  afTorded  by  the  demon- 
stration of  bacteria  as  essential  agents  in  the  i)roduction  of  many  affec- 
tions promised  a  new  field  of  research,  which,  during  the  last  decade, 
has  yielded  so  abundantly  that  it  now  becomes  possible  more  fully  to 
interpret  manv  facts  ].reviously  unapj-re.  ^.t.-d  ..r  t.-t.dlx-  r.bsrure. 

8 


98 


GEXKRAL    PATHOLOGY. 


The  exhaustion,  accumulation,  and  related  theories.  Klebs  and  Pas- 
teur believed  that,  in  the  first  attack,  something  in  the  system  essential 
to  the  life  of  the  organisin  became  exhausted,  and  the  germ  died.  A 
recurrence  of  the  disease  wholly  depended  upon  a  renewal  of  this  sub- 
stance, and  in  the  interim  the  person  possessed  an  immunity  to  the 
disease.  Chauveau,  supported  by  many  eminent  bacteriologists,  be- 
lieved that  the  immunity  depended  upon  the  accumulation  in  the  sys- 
tem of  bacterial  products  that,  having  arrived  at  a  certain  degree  of 
concentration,  are  incompatible  with  germ  life. 

Grawitz  explained  the  induction  of  immunity  by  assuming  that  in 
infectious  diseases  a  conflict  between  the  cells  of  the  body  and  the 
germs  of  disease  ensues  immediately  upon  the  introduction  of  the  latter 
into  the  tissues.  If  the  cells  are  victorious  in  the  combat,  they  ever 
after  should   possess  increased  power  of  resistance  to   this  particular 

germ,  and,  in  fact,  be  able 
to  destroy  it  immediately 
upon  its  entrance  into  the 
tissues. 

Biichner  promulgated 
an  explanation  that  was  a 
slight  modification  of 
Grawitz's  hypothesis.  He 
assumed  that  in  every  in- 
fection there  is  an  inflam- 
matory reaction  at  the 
point  where  the  germs 
localize,  and  that  an  alter- 
ation in  the  cells  is  thereby 
induced  that  subsequently 
enables  the  cells  of  the 
economy  to  resist  and  de- 
stroy that  particular  germ. 
Metchnikoff  next  ad- 
vanced the  theory  of 
phagocytosis,  which  he  has 
enthusiastically  defended 
through  all  the  contro- 
versy that  has  arisen  since 
its  introduction,  and,  by  adapting  it  to  newly  acquired  facts,  has 
succeeded  in  maintaining  for  it  a  position  in  the  first  rank  among 
the  various  explanations  that  have  been  offered  for  the  phenomena 
of  immunity.^  He  believes  that  the  ameboid  cells  of  the  body 
take  into  their  substance  the  bacteria,  just  as  they  would  a  particle 
of  foreign  matter  or  an  article  of  food,  and,  appropriating  a  portion 
to  their  own  use,  throw  oflf  the  remainder  into  the  blood,  to  be 
carried  to  and  excreted  by  the  emunctories.  Although  many  cells  of 
the  body  are  competent  to  perform  the  function  of  phagocytosis,  the 
typical  phagocytes  are:  (i)  The  microphagocyte  of  Metchnikoff,  iden- 
tical with  the  neutrophile  and  amphophile  cells  of  Ehrlich,  or  the  finely 
granular  oxyphile  cell  of  Kanthack  and  Hardy;    (2)  the  macrophago- 

*  A  full  presentation  of  Metchnikoff's  views  will  be  found  in  his  work  en- 
titled "Immunity  in  Infectious  Disease,"  1904,  English  translation. 


Fig.  55. — Cells  from  Exudate,  Case  of  Empyema. 
The  large  hyaline  cells  (macrophagocytes)  contain  many  pneumo- 


HACTKkIA    AS   CAUSES  OP  DISEASE. 


09 


cyte  of  Metchnikott.  or  lar^'c  lymphocyte  of  Khrlich.  or  hvaline  i. 
Kanthack  and  Hardy;'  (3)  endothelium,  particularlv  the  endothelial 
cells  of  the  Mood  capillaries,  and  partly,  altliou^^di  to  a  somewhat  un- 
known extent,  the  endothelium  of  the  lymphatics,  and  even  larj^'c 
lymph-si)aces,  such  as  the  serous  membranes;  (4)  other  mesoblastK- 
cells,  particularly  durinj,^  active  proliferation  or  when  subjected  to  irri- 
tation. In  this  last  group  belong  the  polyblasts  and  hbroblasts  of 
embryonic  and  granulation  tissues,  and  possibly  similar  cells  produced 
under  other  circumstances.-  Leishmann  ^  has  devised  a  method  of 
measuring  the  phagocytic  power  of  leukocytes.  Wright  and  Douglas  * 
have  shown  that  in  the  blood-plasma  and  serum  there  are  certain 
substances  which  in  some  way  not  yet  accurately  determined  so  act 
upon  and  alter  the  bacteria  that  phagocytosis  more  readilv  can  take 
place.  The  bodies  possessing  this  quality  are  called  opsonins ;  thev 
are  rendered  inert  by  temperatures  of  60°  C.  to  65°  C. 

Xuttall,"'  Buchner."  and  others  having  demonstrated  the  bacterial 
powers  of  the  blood.  Fodor  was  led  to  believe  that  immunity  depended 
upon  the  presence  in  the  body-fluids  of  materials  destructive  to  the 
bacteria.  Biichner  and  Hankin  showed  the  presence  in  the  blood 
of  certain  bodies  they  called  alexins,  and  upon  the  activity  of  which 
immunity  was  believed  to  depend.  It  was  shown,  however,  that  the 
bactericidal  properties  of  the  various  sera  did  not  prevent  the  cultiva- 
tion of  bacteria  upon  them,  nor,  when  such  sera  were  taken  from  animals 
naturally  immune  and  injected  into  susceptible  animals,  did  they 
produce  immunity.  Metchnikoft"  held  that  the  protective  agencies  iii 
the  sera  arose  from  phagolysis  (dissolution  of  the  leukocytes)  and  the 
retention  in  the  blood  of  the  anti-infectious  agent  normallv  produced 
and  found  within  the  phagocytic  cells.  As  a  result  of  these  observations 
there  has  gradually  been  evolved  the  cellulohumoral  theory  of  immu- 
nity, which  best  accords  with  the  facts  established  by  ex{)erience  or 
elucidated  by  research.  This  theory  presumes  that  there  are  certain 
"iDiti-hodics"  present  in  the  cells  and  body-juices  of  an  animal,  no  matter 
what  form  of  immunity  it  may  possess.  As  the  name  indicates,  the 
cellulohumoral  theory  is  based  upon  the  belief  that  these  .substances 
are  present  in  the  body-juices  as  well  as  in  the  cells,  while  at  the 
same  time  the  tendency  of  investigators  is  to  beheve  that  these  pro- 
tective agents  are  produced  by  the  somatic  cells. 

In  tSq7  Ehrlich  announced  his  hypothesis,  known  as  the  side-chain 
theory  of  immunity,  which  has  largely  replaced  the  older  views.  While 
necessarily  somewhat  complex,  it  best  explains  many  facts  which  other 
theories  less  clearly  elucidated.  Like  MetchnikolT's  theory  of  p!iat,">- 
cytosis.  Ehrlich's  explanation  is  based  u|»on  normal  nutritional  ;  • 
in  the  body-cells.  The  former  oliserver  lield  that  the  leukocyte  ' 
its  nutrition,  at  least  in  part,  by  englobulating  food  particles  coming 

'  For  cla.ssification  and  description  of  these  leukocytes  see  tabic  in  chapter  ur. 
Patholog}-  of  the  Blood.  Part  III.  Chapter  I. 

'  For  further  consideration  of  phagocytosis  the  reader  is  referred  to  the  article 
on  Inflammation. 

'  "Brit.  Med.  Jour."  Jan.  11,  1902,  p.  73. 

*  "Proceedings  of  the  Royal  Society,"  vol.  72,  p.  357.  also  vol.  73,  1904.  p- 
T,yS.  and  "Lancet,"  1904,  vol.  ii,  p.  1138. 

'  "Zcit.  f.  Hvp.."  Bd.  iv,  p.  ^53. 

«  "Centralbl!  f.  Bakt."  Bd.v.  p.  821. 


lOO  GENERAL    PATHOLOGY. 

within  its  reach,  and  this  physiologic  attribute  of  the  ceU  became  a  protec- 
tive mechanism  in  the  destruction  of  bacteria.  Ehrhch  assumes  that  each 
cell  possesses  special  chemic  affinities  which  enable  it  to  attract  and 
attach  to  itself  substances  necessary  for  its  nutrition;  he  compares  these 
hypothetic  l)odies  to  the  side-chains  of  certain  chemicals  having  highlv 
complex  molecules.  Diagrams  illustrating  the  theory  necessarily  con- 
vey the  impression  that  these  side-chains  are  morphologic  entities: 
such,  however,  is  not  the  case.  The  structure  of  cells  gives  no  hint 
of  the  presence  of  such  bodies;  they  are  chemic  and  not  morphologic 
parts  of  the  cells.  It  is  supposed  that  in  the  normal  nutrition  of  the 
cell,  each  food  molecule  that  it  assimilates  enters  by  a  different  chemic 
combination  with  the  cell  protoplasm.  This  path  by  which  the  cell 
takes  food  constitutes  what  Ehrhch  originally  termed  a  side-chain, 
but  which  later  he  designated  a  receptor  ;  necessarily  the  :nultitudinous 
receptors  by  which  each  cell  obtains  its  nutrition  must  differ  chemicallv, 
and  the  receptors  of  different  cells  must  also  be  dissimilar.  Toxins 
circulating  m  the  blood  are  attached  to  the  cell  by  the  same  mechanism 
as  the  nutritional  elements;  in  other  words,  by  the  receptors.  If  the 
quantity  of  the  poison  be  sufficient,  the  cell  is  destroyed.  If,  on  the 
other  hand,  the  poison  be  in  small  amounts,  the  particular  receptors 
only  are  affected.  Weigert  called  attention  to  the  fact  that  in  the  pro- 
cess of  repair  the  tissues  always  manifest  a  tendency  to  exceed  the  abso- 
lute requirements  for  the  restitution  of  structure,  and  Ehrlich  applied 
this  observation  to  explain  the  formation  of  antitoxin.  If  a  given 
receptor  or  set  of  receptors  is  constantly  attacked,  the  tendency  of 
the  cell  will  be  to  reproduce  these  structures  in  increasing  quantities. 
Eventually  the  surplus  receptors  are  thrown  off  into  the  body-fluids 
with  which  they  circulate.  If  the  poison  enter  the  circulation,  the 
fluids  of  which  are  already  surcharged  with  suitable  combining  elements 
(receptors),  it  becomes  at  once  attached  to  these  substances,  is  neutral- 
ized, and  the  cells  escape.  The  free  receptors  circulating  in  the  blood 
and  possessing  the  power  to  neutralize  toxins  are  the  antitoxins. 

It  will  be  observed  that  the  theory  just  outlined  offers  an  explana- 
tion for  (i)  natural  immunity  in  which  it  is  possible  to  conceive  that 
(a)  the  cells  of  the  immune  animal  possess  no  receptors  suitable  for 
the  particular  poison,  or,  (6)  the  body-fluids  of  the  animal  may  be 
surcharged  with  receptors  which  anchor  the  incoming  poison  and  pre- 
vent it  from  attacking  the  cell.  (2)  It  gives  a  satisfactorv  reason  for 
the  occurrence  of  acquired  immunity,  whether  produced  by  an  attack 
of  the  disease,  the  administration  of  bacterial  products,  dead  or  living 
bacteria,  or  by  other  methods  of  vaccination.  (3)  It  elucidates  the 
occurrence  of  passive  immunity  produced  by  injecting  the  blood  or 
serum  of  an  immune  into  a  non-immune  animal.  (4)  It  explains  the 
presence  of  antitoxin  in  the  blood  and  gives  an  adequate  reason  for  its 
continued  manufacture  by  the  cells.  (5)  The  receptors  attacked  are 
those  having  special  affinities  for  the  poisons  influencing  them,  and  as 
these  only  are  regenerated,  it  becomes  evident  why  antitoxic  substances 
possess  such  striking  speciflcity — the  antitoxin  of  diphtheria  neutralizing 
the  poison  of  that  organism,  the  antitoxin  of  tetanus  neutralizing  the 
poison  of  the  tetanus  bacillus,  but  neither  antitoxin  exerting  any  specific 
influence  upon  the  poison  produced  by  the  other  organism.  (6)  Aside 
from  its  application  to  the  problem  of  immunitv,  this  theory  also  offers 


MACTKkIA    AS   CAUSKS   O  I-    DISKASK.  ,ui 

an  explanatioa  lor  the  well-known  fact  that  infectious  diseases  aic 
characterized  hy  the  occurrence  of  a  more  or  less  definite  time  between 
exposure  to  infection  and  the  development  of  symptoms;  this  is  ordi- 
narily called  the  period  of  incubation,  and  corresponds  to  the  time 
necessary  for  the  specific  or},'anism  to  ^'rnw  and  produce  its  poison  and 
jiermit  this  toxin  to  attack  the  cells  with  sufficient  intensity  tf)  disturb 
their  function  and  give  rise  to  sym])tf)ms. 

Ehrlich  found  that  he  couki  immunize  animals  to  such  poiscins  as 
abrin  and  ncin.  and  that  the  process  of  tissue  immunization  is  not 
restricted  to  antagonism  against  bacterial  poisons  alone.  It  has 
been  shown  by  a  numl)er  of  observers  that  it  is  possible  for  the 
toxin  molecule  to  manifest  a  great  reduction,  amounting  in  some  in- 
stances almost  to  an  entire  loss  of  its  toxic  properties,  although  it  still 
retains  its  power  to  coml)ine  with  the  antitoxin.  Such  toxins  art- 
called  toxoids.  The  demonstration  of  this  fact  led  Ehrlich  to  the  con- 
ception that  the  toxin  molecule  possessed  two 
groups;    one    bv    which    union     with    the    cell  ' 

occurred,  haptophore  group,  and  the  other  bv 
which  the  desiructive  action  of  the  toxin  is 
manifested — the  toxophore  group.  The  combin- 
ation between  toxin  and  antitoxin  resembles 
chemic  union  in  that  it  is  more  rapid  at  high 
temi)eratures  than  low,  and  less  intimate  in 
weak  than  m  concentrated  solutions;  further, 
it  follows  the  law  of  multiples,  as  shown  by  the 
fact  that  if  the  cjuantity  of  antitoxin  necessary 
to  neutralize  the  minimum  lethal  dose  of  the  Cell 

toxin  is  increased  ten  times  and  mixed  with  ten      i-K..56.-pi ag»amIi.ustrai 
minimum    lethal    doses,    neutralization    will    be  cKRN!i'"r'''THif  u.mos*^bi 

complete.^  twf.>;.v  Toxiv  a.nt>  Cr.u.. 

It  will  be  seen  that  the  foregoing  summary       ••  ^ITe'' M^iw' ^LrJ't.f )' 
of  Ehrlich's  views  explains  the  phenomena  of  'he  luipiophorc  group     /• 

■         .  '  .  Cell    rfCfplor.      E.    h.    A     ■■'• 

antitoxic  immunity,  but  tor  reasons  given  below  /on  not  aaaptcd  to  m.r   • 

must  be  modified  in  order  to  elucidate  bacterio-  ,oi"„  .^'but  mtuht'*''' 

Ivtic    immunitv.      Recent   studies   in   cvtolvsis.  with  other  tuxii«  i«.>-. 

...  ']        ■       1  t  .Li      ...  ...I.  ■  '  ap|)ropnatc     haptoph.f 

especially  hemolysis,  have  shown  that  the  process  uroups. 

Ity  which  the  protective  forces  of  the  body  an- 
tagonize foreign  blood-cells  operates  in  a  manner  essentially  identical  with 
the  methods  by  which  bacteria  are  destroyed.  It  is  evident  that  entirely 
dififerent  agents  accomplish  the  destruction,  but  their  methods  of  operation 
appear  to  be  identical.  In  consideration  of  this  type  of  immunity  it  is 
to  be  borne  in  mind  that  the  statements  which  follow  applv  to  bac- 
teriolysis' and  cytolysis,  bacteriolytic  and  cytolytic  immunities.  As 
already  stated.  Fodor.  Xuttall.  Biichner.  and  others,  have  shown  that 
blood-serum  jjossesses  the  power  of  destroying  bacteria.  Buchncr 
attri])uted  this  (juality  to  substances  he  called  alexins.  It  was  first 
demonstrated  by  Bordet  that  if  bacteriohtic  blood  or  .serum  be  sub- 
jected to  a  temperature  of  56"  C.  for  half  an  hour,  the  cytolytic  or 
bacteriolytic  property  was  lost  and  the  serum  rendered  inactive.  If 
to  this  inactivated  serum  there  was  atlded  a  small  quantity  of  blood 
or  serum  from  an  animal  of  the  same  species  not  immunized  to  the  par- 
'  For  standardizing  antitoxin  see  chapter  on' BactcrioloRic  Technic. 


GEXERAL    PATHOLOGY 


ticular  germ  or  cell  upon  which  the  experiment  was  being  conducted, 
the  inactivated  fluid  reacquired  its  property  of  destroying  the  germ 
or  other  cell;  in  fact,  became  reactivated.  This  experiment  clearly 
demonstrated  that  cytolytic  and  bacteriolytic  activities  depend,  in  each 
instance,  upon  the  presence  of  two  substances,  one  of  which  is  destroyed 
at  56°  C.  (thermolabile  body),  the  other  resisting  higher  temperatures 
(thermostable).  The  substance  present  in  normal  blood  and  easily 
rendered  inert  by  heat  is  called  the  complement,  alexin,  cytase  or  addi- 
ment.  In  the  following  description  the  term  complement  will  be  used. 
The  heat-resisting  substance  is  known  as  the  intermediary  or  interme- 
diate body,  immune  body,  substance  sensi- 
bilisatrice,  amboceptor,  fixator,  sensitizer, 
philocytase,  copula,  desmon,  preparator, 
and  immunisin;  of  these,  amboceptor  and 
immune  body  are  commonly  employed. 
For  the  production  of  cytolysis  or  bac- 
teriolysis it  is  necessary  for  the  cell  to 
possess  a  receptor  the  molecular  constitu- 
tion of  which  is  adapted  to  combination 
with  the  cyto'phile  haptophoric  group  of 
the  immune  body,  the  latter  in  turn  com- 
bining by  its  complementophile  group  with 
the  haptophoric  group  of  the  complement ; 
the  zj'-motic  group  of  the  complement  acts 
through  the  chain  formed  by  the  fore- 
going combination.  The  absence  of  any 
one  of  these  conditions  prevents  the  occur- 
rence of  cytolysis.  A  solution  containing 
both  immune  body  and  complement  may 
be  deprived  of  either,  leaving  the  other, 
which,  if  injected  into  an  animal,  gives 
rise  to  an  antibody  possessing  the  power  of 
antagonizing  or  neutralizing  the  substance 
used  in  the  injection.  As  already  stated, 
serum  heated  to  55°  or  56°  C.  is  inactivated 
as  a  result  of  destruction  of  the  comple- 
ment; it  still  contains,  however,  the  im- 
mune body.  The  removal  of  the  latter 
substance  from  the  mixture  containing  both 
is  somewhat  more  complex,  but  may  be 
accomplished  in  the  following  manner :  If 
the  serum  of  a  rabbit  immunized  to  bovine 
red  blood-cells  be  mixed  with  the  bovine  erythrocytes  at  ordinary  tem- 
peratures, hemolysis  occurs;  if,  however,  the  mixture  is  kept  at  or  about 
0°  C. ,  the  immune  body  combines  with  the  cells,  hemolysis  being  prevented 
by  the  fact  that,  at  this  temperature,  the  complement  is  inactive.  The  red 
cells  may  be  removed  by  sedimentation,  and  if  redistributed  in  a  solution 
containing  complement,  at  the  proper  temperature,  promptly  undergo 
hemolysis.  It  can  be  shown  that  the  fluid  from  which  the  red  cells 
were  removed  still  retains  the  complement.  The  method  by  which 
anticomplement  and  anti-immune  body  intervene  in  the  prevention  of 
hemolysis  is  indicated  by  the  accompanying  diagram  (see  Figs.  58  and  59). 


Cell 


Kir,.  57. — Diagram  Illustrating  Ehr- 
i.ich's  Views  Concerning  the 
Union  between  Complement,  Im- 
>ruNE  Body,  and  Cell  in  the 
Process  of  Cytolysis  Including 
Hemolysis   and   Bacteriolysis. 

A,  Complement  of  which  B  is  the  zymo- 
toxic  or  cytoto.xic  group  and  C  the 
haptophore  group  which  at  D  joins 
with  the  complementophile  group  of 
the  amboceptor.  E,  Amboceptor  or 
immune  body  of  which  F  is  the  com- 
plementophile group  and  G  the  cyto- 
phile  haptophoric  group.  H,  Cell 
receptor.  /,  /,  Receptors  not  adapted 
to  combination  with  the  particular 
immune  body  E,  but  might  combine 
^\^th  other  amboceptors  possessing 
appropriate  cytophile  haptophoric 
groups. 


KACTKKIA   AS  CAUSES  OF   DISEASE. 


103 


The  scope  of  this  work  does  not  permit  a  (hscussion  rif  the  muhi- 
plicity  of  comi)lcment  or  tlie  hniitations  witliin  winch  the  immune  ])0(lv 
is  specific.  E.xperinients  seem  to  in(hcate  that  there  is  more  than  one 
complement  and  that  the  immune  body  within  certain  limits  is  specihi .' 
With  regard  to  the  source  of  the  complement,  Metchnikoff  and 
his  students  strongly  maintain  that  it  is  derived  from  the  leukocytes, 
assuming  its  ])roduction  by  the  microphagocyte  or  the  macrophago<ytt'. 
he  recognizes  two  tyi)es,  the  microcytase  and  the  macrocytase.  Abbott 
and   Bereev  have  shown  that   alcohol    niav  decrease  or  attenuate  th»- 


Cell 


Cell 


Fig  58.  Pic.  so. 

Diagram  illustrating  Ehrlich's  views  concerning  the  .Tclion  of  (Fig.  eSI  ami  immum-  IkmIv.  an<i  (Fig.  5f>>  .inii- 
comrJcment  in  preventing  cytolysis,  including  hemoly.sis  and  liaitiTiolysis.  A'  (Fig.  .sS),  .^ntiimmunr  UhIv 
or  anti-amboccplor.  Y  (Fig.  59),  .\nti-complcraent.  The  other  letters  have  the  >.ime  significance  in  l»«ih 
figures. 

Complem.-nt  of  which  B  is  the  zymotoxic  or  c>totoxic  group  and  C  the  haplophure  group,  which  in  the  firs! 
figure  combines  at  D  with  the  complemcntophile  group  of  the  amlMxri.ii.r  •<r  immune  l)ody;  in  ttu  wi.  n<l 
figure  this  combination  is  prevented  by  the  intervention  of  the  an-  ■    >'.     E.  In"-  r 

amboceptor,  of  which  F  is  the  complemcntophile  group  and  G    tl  >ptophoric  .:r 

the  second  figure  combines  with  the  cell  receptor  H;   in  the  first  fi^'  mation  is  pr^  >■ 

intcrNX-ntion  of  the  anti-immune  body  or  anli- amboceptor  A'.  /.  /,  Kci.ipior.>  not  adapted  to  LuiiiLnnjUin 
with  the  particular  immune  body  £,  but  might  join  other  amboceptors  having  appropriate  cytophile  hap- 
lophoric  groups. 

It  will  be  seen  that  either  anti-amlxKeptor  or  anti-complement  prevents  cytolysis,  including  hemolyMS  and  bac- 
teriolysis, by  interfering  with  the  combination  of  complement,  immune  body,  and  cell  rcccptpr.  all  three  of 
which  must  unite  in  order  to  act  on  the  body  cell  f>r  germ. 


complement.  Ehrlich  and  .Morgenroth  found  that  phosphorus  produced 
a  similar  action.  Xolf,  Muller,  and  others  have  shown  that  it  is  possible 
to  increase  the  t^omplement.^  Longcope '  has  demonstrated  that  in 
normal  individuals  fluctuations  in  the  bacteriolytic  complement  of  the 

'  Literature  bearing  on  multiplicity  of  complements  and   specificity  "' 
mune  bodies  is  widely  distributed.      In  addition  to  the  references  given  on  pri 
ing  pages  see  Pearce.    "Albany  Med.  .\nnals,"  Aug.,  1004;    als«)  Longcopc's  article 
cited  below,  and  Wultmann,  "Jour.  <>i  Exp.  .Med.,"  vol.  vii.  \<>.  2. 

^  For  interesting  experiments  on   this  subject  and  citations  from  litem* 

see  Sweet,  "Univ.  of  Penna.  Med.  Bull."  December,  iqoi. 

'   "L'riv  >•<'*••  "t   T'>TiTi;i     \\i  A     T^nl!      '     V.  ■'.  <  mbir     mr.^ 


104  f.EXERAL    PATHOLOGY. 

blood  occurs,  and  that  in  many  chronic  affections,  such  as  nephritis, 
cirrhosis  of  the  hver,  and  diabetes,  there  is  a  marked  decrease  in  the 
complement,  and  that  terminal  and  agonal  infections  are  probably 
due  to  this  fact. 

Welch'  has  made  a  most  suggestive  extension  of  Ehrlich's  receptor 
theory ;  he  inquires  whether  it  would  not  be  possible  for  the  living  germ 
to  react  to  the  body-cells  and  juices,  just  as  Ehrlich's  views  indicate 
that  the  body-cells  are  led  to  produce  antisubstances  by  stimuli  coming 
from  the  bacterial  poisons.  This  implies  that  the  bacterial  cells  are 
possessed  of  receptors  which,  when  damaged  by  combination  with  hap- 
tophore  groups  produced  in  the  tissues  of  the  host,  would  lead  to  re- 
action on  the  part  of  the  geim  which  in  turn  might  produce  and  liberate 
receptors  in  excess,  just  as  the  animal  cells  are  supposed  to  do.  This 
suggestive  hypothesis  explains  how  it  is  possible  to  augment  the  viru- 
lence of  a  given  germ  by  successive  inoculation  into  animals.  Walker - 
has  shown  that  bacteria  cultivated  on  immune  sera  become  more 
virulent,  thus  indicating  that  something  in  the  culture  medium  stimu- 
lates the  germ,  giving  rise  to  increased  toxin  production  or  the  elabora- 
tion of  poison  possessing  heightened  toxicity. 

Pfeiffer  found  that  if  cholera  spirilla  were  introduced  into  the  peri- 
toneal cavity  of  rabbits  immunized  to  that  organism  the  bacteria  became 
motionless,  collected  in  groups  (agglutination),  and  finally  dissolved 
(bacteriolysis).  This  observation  (Pfeiffer's  phenomenon)  was  the 
starting-point  of  many  experimental  studies,  and  it  was  thought  for 
a  time  that  agglutination  was  a  necessary  part  of  bacteriolysis;  this 
IS  now^  known  not  to  be  the  case.  Although  agglutination  occurs  in 
various  forms  of  cytolysis,  the  agglutinins  resist  temperatures  (60°  C.) 
destructive  to  the  complements  active  m  bacteriolysis.  A  serum  that 
is  both  agglutinative  and  bacteriolytic  may  be  deprived  of  the  latter 
property  without  loss  of  the  former.  It  has  been  shown  that  agglutinins 
possess  a  haptophore  and  an  agglutinophore  group,  and  that  the  cells 
(bacterial  or  somatic)  influenced  by  these  agents  contain  an  agglntinable 
substance  which  in  turn  possesses  two  haptophore  groups.  Develop- 
ment of  agglutinins  in  the  blood  of  patients  suffering  with  certain 
diseases  has  been  shown  to  possess  high  diagnostic  value,  particularly 
in  typhoid,^  paratyphoid,  and  Malta  fevers.  It  has  been  found 
that  the  blood-serum  in  malaria  contains  agglutinins  for  the  erythro- 
cytes of  the  noninfected,  and  that  under  certain  conditions  agglutinins 
for  animal  parasites  (trypanosomes)  may  develop. 

Precipitins. — If  an  animal  receives  subcutaneous  or  intra-abdominal 
injections  of  the  cell-free  serum  of  an  animal  of  a  different  species,  or 
the  expressed  juices  of  the  tissues  of  the  second  animal,  or  egg- albumen, 
peptone,  milk  or  whey,  or  even  urine,  there  develop  in  the  animal  ex- 
perimented upon  substances  which,  when  added  to  clear  fluids  containing 
minute  quantities  of  the  substance  with  which  the  animal  w^as  injected, 
give  rise  to  a  precipitate.     The  delicacy  and  extreme  sensitiveness  of 

'  Huxley  Lecture  on  Recent  Studies  on  Immunity,  reference  in  foot-note  on 
page  94' 

^  "Jour,  of  Patholog\'."  March,  1902. 

^  For  method  of  Widal's  test  in  the  diagnosis  of  typhoid  fever  see  chapter  on 
Bacteriologic  Technic.  Review  of  literature  on  the  subject  by  Rosenberger. 
Publications  from  the  Laboratories  of  the  Jefferson  Medical  College  Hospital, 
vol.  i.  I0O4- 


HACTKRIA    AS   (At'SKS   ( )  I'    DISK  ASi;.  IO5 

this  roattion  are  ainoni,'  tin-  strikini,'  additions  to  orj^anir  ehcmistry. 
These  agents  resist  60°  C\,  hut  are  rendered  inactive  by  tempera- 
tures near  70°  C.  Witliin  certain  hmits  the  action  of  j)recii)itins 
approaches  specificity.  Tlie  serum  of  an  animal  immunized  to  Iniman 
albumens  reacts,  although  with  less  intensity,  to  the  serum  of  the  higher 
ape:  rabbits  immunizeti  to  chicken  serum  yield  a  precipitin  that  also 
reacts  with  pigeons,  and  animals  immunized  with  albumen  derived 
from  the  egg  of  the  chick  produce  sera  containing  j)reci|)itins  for  the 
egg-albumen  of  closch'  related  birds.  Precipitins  arc  useful  for  the 
identification  of  blood  in  medicolegal  cases  and  may  be  u.sed  for  the 
recognition  of  horse-meat  and  dog-meat  in  sausages,  and  are  also  of 
value  in  showing  the  relation  existing  l)etween  closely  allied  animal 
species.' 

'  For  hteraturc  of  ])rfcii)itins  sic  Xultall,  "Blood  hnnuinity  and  Blood  Ri- 
lationship,"  1004.  The  medicolegal  value  of  the  test  is  discussed  by  Nuttall. 
also  Ewinjj  ami  Strauss,  "Medical  Xews."  Xov.  7  and  14,  i<jo^. 


CHAPTER  V. 

BACTERIA    AS    CAUSES    OF    DISEASE.— (Continued.) 

THE  INFECTIONS. 

PATHOGENIC  SCHIZOMYCETES 

Morbid  Processes  Due  to  Disease-producing  Bacteria. 

The  schizomycetes  or  bacteria  include  the  largest  number  of  vege- 
table organisms  producing  disease.  Of  the  many  classifications  dividing 
the  larger  group  into  smaller  subclasses,  none  has  been  fully  satisfactory; 
the  most  convenient  division  is  based  upon  morphologic  peculiarities, 
which,  by  taking  some  liberties,  permits,  the  recognition  of  three 
more  or  less  distinct  groups :  (I)  Cocci;  (II)  baciUi;    (III)  spirilla. 

I.  Cocci. — Spheric,  slightly  ovoid,  or  lancet-shaped  bacteria,  which 
reproduce  by  binary  division,  and  occasionally  by  the  formation  of 
arthrospores. 

The  cocci  form  such  complex  varieties  that  a  further  subdivision  will 
be  necessary  to  facilitate  our  study  of  them : 

f   Monococci  1^  Streptococci. 

Bv  number       Diplococci.'  By  arrangement  \  ^^icrococci  (staphylococci). 

1  Tetracocci.  Ascococci. 

[  barcmse. 

Varieties. — Monococci :  cocci  not  definitely  associated  in  any  manner 
with  one  another.  Diplococci:  cocci  associated  in  pairs.  Tetracocci: 
cocci  associated  in  fours.  Streptococci:  cocci  arranged  in  chains,  which 
may  contain  thirty  or  more  elements.  Micrococci  (staphylococci):  cocci 
growing  in  irregular  masses;  the  individual  elements  are  embedded 
in  a  gelatin-like  substance  elaborated  by  the  organisms.  Ascococci: 
cocci  associated  in  circular  or  globular  masses  (zooglea)  held  together 
by  a  gelatinous  substance.  Sarcinas:  cocci  arranged  in  packets  or 
cubes  of  eight  or  more  elements. 

II.  Bacilli. — Rod-shaped  organisms,  motile  or  nonmotile,  rigid 
or  flexible.  The  organism  formerl}^  described  as  a  bacterium  is  included 
in  this  class. 

III.  Spirilla. — It  is  necessary  to  divide  the  spirilla  into  two  groups. 
In  one  of  these  the  spirils  are  rigid  and  relatively  short;  the  spirillum 
of  Asiatic  cholera  possesses  these  characters.  In  the  second  type  the 
organisms  are  longer,  more  flexible,  and  the  disparity  between  length 
and  thickness  much  greater  than  in  the  first  type ;  organisms  possessing 
these  characters  have  been  found  in  relapsing  fever,  and  more  recentl}* 
in  syphilis.  There  are  reasons  for  believing  that  the  long,  undulating, 
actively  flexible  spirils  are  not  bacteria  but  properly  belong  with  the 
unicellular  animal  parasites.  This  view  is  further  supported  by  the  fact 
that  in  neither  relapsing  fever  nor  syphilis  has  the  parasite  been  culti- 
vated. 

io6 


i\i    rii.'iv    \s  (    \  fsi-:s  ( )i"  DISL-\! 


Siircina;  (packet  coccij. 


•!t^ 


Staphylococci. 


letiacfxii. 


f  Ciliated  cell. 
I 
Flagellate  I 
Bacilli.  1 

I 

I     Spider  cell. 

f  Diplococcu.s 

^^■'l'' "P   !  Tetracoccus 
sules 

i  MonocDCcus 

Centrally  situated  spores 

Clostridia  forms 

Knobbed  bacteria  with  ' 

terminal  sixjres.  i 

Fig.  6o.-Diaok.\m  1llistrati.no  tut.  Nomenclature  or  Schjzomyc-ete-s  Based  upon  their  Morpiiolooy 
(After  Schenk.)     X  about  700  diameters. 

Sarcin;c  include  the  packet  cocci;  cocci  arranged,  in  more  or  less  cuboid  shapes,  a-s  multii' 
contains  8,  16.  32.  or  more  units.     The  coed  proper,  incluile  those  named  by  tlv 
group,  as:    (a)    Monococci,  or  cocci  with  no  special  arningcmcnt  or  er"<ii>inu' 
staphylococci.     (6)    Diplococci.  or  cocci  grouped  in  pairs,     (c)     I'r'r 
second  method  of  naming  is  by  arrangement,  as:   (.-1)   Streptocixti. 
or  encapsulated  grouped  cocci;    (C)  staphylococci,  or  cocci  presiinv' 

The  student  will  fail  to  detect,  under  the  microscope,  the  diflt  i  ■  _l 

coed.     The  term  "zooglea"  is  applied  to  agminated  masses  ■  '  "^*i^ 

like  ma.ss  of  gelatinous  material  elaborated  by  the  microlx".      I 
teria.     The  spiroch.x-ta  are  tie.xibic  spirals,  such  as  the  organism  ui  re,  i|-iu,:  i.  >.  . 


Slender  badlK. 

Short  badlli. 

Bacilli  in  chains  (sireplol>acilli» 

Vibrio  (spirillum). 

Comma  bacilli. 
Spirochitta. 


PATHOGENIC  COCCI. 
The  gonococcus'    (Xeisser.   1879)  is  a  roll   or  biscuit-shaped,  non- 
motile,  aerobic  -liplococcus,  0.8  »  to  1.6  ,/  in  diameter.     Cultures  may  be 
obtained  on  human  blood-serum,  or  on  media  contaming  that  substance. 

'  Muir  and    Ritchie-,  American  edition,  edited  by  H. "'■    v,  t,  r,  ti<  .- 

important  articles  up  to  1902.      Pinto,    'Jour,  de  Phys.  < 

i^     1004    p.   105.S.     "Cultivation.  Toxins,  etc."      Eltmg. 

March    1900.     Wvnn.    -Lancet,"  Feb.  11.  1905,  -General  Ln..iioc.j^cu>  . 

Kimball,   "Med.   Record."  Nov.   14.   IQ03.  '•Gonwoccus  lnff>rtio,m    1. 

Krause,  "Berl.  klin.  Woch.,"  Mav  q,  1004.    'Gonorrheal  - 

Med.    Tour..  '   March   18,   IQ05,   '-Gonricoccus  Infection  u 

Med.  Diss.  Konigsberg.  1904.  •'Cultural   Character^  and  i'i;i^T;. 


loS 


GENERAL    PATHOLOGV. 


also  on  acid  urine  agar  and  l)lood-smeared  agar;  Wertheim's  medium' 
may  be  used.  The  organism  develops  slowly,  appearing  twentv-four 
to  thirty-six  hours  after  inoculation  as  a  smooth,  thin,  grayish-yellow, 
moist  film  with  ill-defined  margins;  later  the  margins  become  jagged 
with  sharper  definition.  The  optimum  temperature  is  ,^3°  C.  to  37°  C, 
the  maximum   7,8°  C,  and  the  minimum  25°  C. 

DeDwnstratioii. — Make  spreads  and  fix  in  the  usual  manner;  stain 
in  alcoholic  solution  of  methylene-blue  five  to  fifteen  minutes;  wash 
with  water  and  restain  for  the  same  length  of  time,  using  a  saturated 
alcoholic  solution  of  eosin.  Wash  in  water,  dry  and  mount.  The 
nuclei  of  the  pus  corpuscles  and  the  gonococci  are  blue,  protoplasm  of 
the  pus  cells  pink.  As  the  organism  does  not  stain  by  Gram's  method 
the  following  technic  may  be  found  useful:  Stain  by  Gram's  method 
followed  by  dilute  carbol-fuchsin  (i  to   10).     Wash  in  water,  dry  and 

mount ;  the  organisms  stained 
by  Gram's  method  are  not 
gonococci,  those  taking  the 
fuchsin  may  be ;  positive 
identification  is  possible  bv 
cultivation  methods  onlv. 
It  also  may  be  stained  by 
any  of  the  basic  anilin  dyes, 
especially  Loffler's  methyl- 
ene-blue. 

Pathogenesis. — Under  or- 
dinary conditions  the  gono- 
coccus  is  pathogenic  for  the 
human  species  only ;  it  pro- 
duces local  infections  on 
mucous  membranes,  particu- 
larly the  urethra,  from  which 
it  may  extend  to  the  bladder, 
ureters  and  renal  pelves, 
seminal  vesicles,  vas,  and 
epididymis;  it  also  causes 
prostatitis.  In  the  female, 
vaginitis  and  vulvovaginitis, 
endocervicitis,  endometritis,  salpingitis,  and  peritonitis  may  be  due  to 
this  organism.  Gonorrheal  peritonitis  is  particularly  prone  to  occur 
in  the  vulvovaginal  lesions  due  to  gonococcus  infections  in  children. 
Gonorrhea  of  the  rectum  is  rare.  Gonorrheal  conjunctivitis,  also  called 
gonorrheal  ophthalmia,  is  a  particularly  destructive  process  most  com- 
mon in  the  new-born,  due  to  infection  by  the  birth  canal,  but  also  re- 
sulting from  accidental  conveyance  of  gonococci  to  the  conjunctiva. 
Nasal,  oral,  and  pharyngeal  gonorrhea  are  rare.  The  lesion  on  the 
mucous  membrane  may  be  acute,  subacute,  or  chronic;    in  the  acute 

and  Cooper,  "Jour.  Amer.  Med.  Assoc.,"  April  2,  1904,  p.  877,  "Gonococcemia. 
Arthritis,  Inflammation  of  the  Tendon  Sheaths."  Harris  and  Haskell,  "Johns 
Hopkins  Hospital  Bulletin,"  December,  1904,  and  Busquet  and  Bichelonne, 
"Gonococcus  Infection  of  Muscles."  Heller,  "Berl.  klin.  Woch.,"  June  9,  1904, 
"Gonorrheal  Phlebitis."  Neneprier,  "Soc.  Med.  des  Hop.  Paris,"  June  23,  1904. 
"Multiple  Netiritis  in  Gonorrhea." 

'  See  chapter  on  Bacteriologic  Technic. 


Fig.  61. — Gonococcus. 
Film  from  urethral  pus.     In  this  specimen  practically  all   thi 
organisms  are  intracellular;    frequently   extracellular  gon 
W&  ococcifare  present. 


BACTKKIA    AS   lAUSKS  OK    DISEASE.  I  Og 

form  the  gonococci  are  partKularly  aNundant  in  the  epitliclial  cells 
and  migrating  leukocytes,  particularly  the  ])olymorphonucU'ars,  but 
arc  also  found  extracellular;  in  the  chronic  lesions  the  organism  is  less 
abundant.  The  gonococcus  has  been  dehnitely  accepted  as  a  pus- 
])rotlucing  organism,  and  in  connective  tissues  may  give  rise  to  distinct 
abscesses,  among  which  should  be  mentioned  peri-urethral  abscess 
and  prostatic  suppuration. 

Systemic  infection  by  the  gonococcus.  The  organism  in  pure  cul- 
ture has  been  obtained  from  the  blood  during  life:  usually  it  enters 
from  infections  of  the  genital  organs,  although  gonococcemia  .secondary 
to  conjunctival  gonorrhea  has  been  reported.  Pinto  and  also  Christmas 
have  shown  that  the  organism  produces  a  toxin  to  which  some  of  the 
systemic  idienomena  may  be  due.  Entering  the  circulation  the  gono- 
coccus mav  give  rise  to  endocarditis,  endarteritis  or  endophlebitis, 
inflammations  of  the  joints,  pericardium,  or  pleura.  Cases  of  gono- 
coccal pyemia  have  been  reported.  According  to  Heller,  there  are 
26  cases  of  gonorrheal  phlebitis  on  record.  Joint  aflfections  are  usually 
monoarticular,  but  may  be  polyarticular.  The  joints  most  frequently 
affected  are  the  knee,  elbow,  and  wrist,  in  the  order  named;  involve- 
ment of  the  smaller  joints  is  not  common.  Usually  the  lesion  stops 
short  of  suppuration;  a  tendency  to  fibrous  ankylosis  is  not  infre- 
iiuently  present.' 

The  Diplococcus  pneumoniae-  (Frankel,  18S4)  is  a  lancet-shaped, 
non-motile,  aerobic  coccus,  usually  associated  in  pairs,  end  to  end. 
and  possessing  a  capsule  which  is  lost  during  cultivation.  In  size  the 
organism  varies;  its  usual  maximum  diameter  is  about  i  ,";  chains  con- 
taining four  to  eight  cocci  occur.      It  may  be  cultivated  on  the  ordinary 

'  For  patholog\'  ot  intlammation  uf  the  mucous  mtmbrant'S  s«.-e  chapttT 
on  that  subject;  also  article  on  Acute  Malignant  Endocarditis  in  chapter  on 
Diseases  of  the  Heart. 

*  See  foot-note.  p.  Si.  Rosenberger,  'Amcr.  Jour,  of  the  Med.  Sci.."  August. 
1903,  article  on  "  Bacteriolog>'  of  the  Blood,"  with  literature  of  Pneumococ- 
cemia.  Rosenau.  ■jour.  Ame'r.  Med.  Assoc.."  March  iS,  1005,  0.871.  Lesieur. 
•Jour,  of  Phvsiol.,"  Xov.  15,  1Q03.  Steuertz,  "Zeit.  f.  klin.  Med.."  1904.  Bd. 
52,  p.  422.  Wolstein,  "Jour,  of  Exper.  Med.,"  vol.  yi.  p.  301,  "Bactcriolojjy  of 
Broncho-  and  Lobar  Pneumonia  in  Infancv."  Hiss.  Ibid.,  p.  317,  "Differ- 
entiation of  Pncumococcus  and  Streptococcus.''  Mathews.  "Annals  of  Surgery." 
November,  1904.  "■  Pncumococcus  Peritonitis."  Anders.  "Amer.  .Med  ."  .March 
18,  1905.]).  4SI.  "Cholecystitis  Due  to  the  Pncumococcus."  Tiz/oni  and  Panichi, 
"Centralbl.  f.^Bakt.,"  1905  (rcf.),  Bd.  xxxvi,  p.  25,  "Latency  of  Pneumococci  ui 
the  Blood."  Patzold.  '-Beitr.  z.  klin.  Chir."  1904.  xliii.  "Necrosis  of  the 
Muscle  in  Pneumococcal  Infection."  Foulerton.  "Trans.  Path.  Sex:,  of  London," 
1902.  vol.  53,  p.  286,  "Pneumococci  Gastritis."  Rossi.  ""Gaz.  degli  Ospcd.e  dcllc 
Clin.,"  Feb.  5.  1905,  "Diplococcemia."  Bullard  and  Sims.  '"Boston  Med.  and 
Surg.  Jour.,"  Dec.  15,   1904.    "Diffuse  Encei)halilis  showing  the  Pneum<x-(X-cus." 

Davies  and  Brown,  "Lancet,"    Oct.  8.  1904,    p.  1017.  "Pneumococcic    !'•   

with  full  bibliograjihv.      Baduel,  "La  Rif.  Med.."  June  2q.    1904.  "Pnev. 
Polvarthritis.""     Bithell.  "Jour,  of    Path,  and  Bact.,"   1904.  "Pncum-c 
Empyema."     Tchistovitch,  "Annales  de  I'lnst.  Pasteui-."  Mav  25.  1904.    "Palho- 
gcnesis  of  the   Pncumococcus."     Ghon,   '"Wien.   klin.   VVcxrh.."   March   10.    1004, 
"p.   267,   "Pneumococcal   Peritonitis,   Historical.  Chemical,  and   Pathological   Re- 
port,"   with    bibliography.      Duckworth    and    Marsh.    "Clin.    Soc.    of    London." 
bin.  8.  1904,  "Pneumococcal  Peritonitis."      Richardson.  "'Jour,  of  Bost 
"Med.    Science,"    vol.    v,   p.    499,    "Pseudo-pneumococci   in    Lobar    Vv 
Spitta,   "Brit.  Med.    Jour.."   Nov.   15,   1902,  p.   579,  "Pneumococcic  I-...- >  ..   .. 
Slaughter,    "".\mer.    Med."   April    18.    1903,   p.   605,   "Record  of  Forty  Cases  of 
Pneumococcic  Arthritis." 


no  GENERAL    PATHOLOGY. 

media,  but  possesses  a  low  vitality  and  grows  best  on  media  containing 
blood  or  blood-serum.  The  colonies  are  small,  discrete,  dew-like,  with 
sharply  defined  edges  not  tending  to  coalesce  but  occasionally  forming 
transparent  moist  films;  does  not  liquefy  gelatin.  The  optimum  tem- 
perature is  37°  C,  maximum  42°  C,  minimum  20°  C.  to  22°  C. 

Demonstration. — The  pneumococcus  stains  with  the  ordinary  anilin 
dyes  and  by  the  usual  methods;  it  is  Gram-positive.  Friedlander 
recommends  staining  the  pneumococcus  in  tissues  as  follows:  Make 
thin  sections,  remove  the  paraffin,  and  stain  for  twenty-four  hours  in 
an  acid  solution  of  gentian-violet,  made  by  mixing  50  parts  of  a  satu- 
rated alcoholic  solution  of  gentian-violet,  100  parts  of  distilled  water, 
and  ro  parts  of  acetic  acid.  After  staining,  decolorize  with  a  one  per 
cent,  solution  of  acetic  acid  in  water  for  one  or  two  minutes,  dehvdrate 
with  alcohol,  clear  with  oil  of  cloves,  and  mount. ^  The  pneumococcus 
is  often  difficult  to  cultivate  from  body  fluids  or  organs  and  is  easiest 
obtained  in  pure  culture  by  inoculating  a  rabbit  or  mouse,  both  of 
which  animals  are  extremely  susceptible.  Media  rich  in  sodium  chlorid 
are  ill  adapted  to  its  growth,  and  it  has  been  suggested  that  sodium 
chlorid  retention  in  croupous  pneumonia  is  a  part  of 
nature's  protective  mechanism.  In  cultivation  it 
1^)  rapidly  loses  virulence,  requires  frequent  transplanta- 

S^  ",1^1?*^     tion,  and  is   best  preserved  in  capillary  tubes  con- 
(^^^  (t^^     taining  sterile  rabbit's  blood.     The  best  medium  for 
^y"^"''^^  securing  cultures  is  peptone  bouillon  containing  eight 

'^  ®®  ^      per  cent,  glucose. 

Pathogenesis. — The    pneumococcal    infections    m 

I'iG.    62. — Diagram    or  .        ,  ,  '-  ,,,,.,,. 

THE  DiPLococcus  Hiau  may  be  local  or  general ;  locally  it  aftects  par- 
iixusTR^AnNG^'^RE-  tlcularly  the  mucous  and  serous  membranes  and 
LATioN  OF  Capsule      lungs."      It   IS    a   spccific    causativc    agent  in  manv 

TO  THE  Contained  i  ,  ,11  1 

Germ.— (c 0  piin  coryzas  and  may  produce  catarrhal  or  pseudo-mem- 
and  Bevan:)  brauous   inflammations  of   the   mucous  membranes. 

It  is  a  frequent  cause  of  serous  membrane  inflam- 
mations, especially  of  the  pleura;  it  also  gives  rise  to  peritonitis 
and  sporadic  meningitis.  Instances  of  epidemic  meningitis  due  to  the 
pneumococcus  are  also  on  record.  Otitis  media  and  inflammation  of 
the  facial  sinuses  are  not  infrequently  of  pneumococcal  origin.  It  occa- 
sionally infects  wounds,  and  has  been  obtained  by  Boyd  from  abscesses  in 
pure  culture.  In  many  individuals  it  is  a  constant  inhabitant  of  the 
mouth  and  nose ;  from  the  latter  cavity  extension  to  the  middle  ear 
and  meninges  may  occur.  In  a  number  of  pneumococcal  infections, 
especially  croupous  pneumonia,  the  organism  enters  the  blood;  in  Rosen- 
berger's  collated  cases  of  pneumonia,  blood  infection  was  present  in 
fifty-three  per  cent.;  once  in  the  circulating  blood  the  pneumococcus 
may  give  rise  to  arthritis,  which  is  sometimes  monoarticular  and 
sometimes  polyarticular.  Davies  and  Brown  have  tabulated  39 
cases  of  pneumococcic  pyemia.  As  a  result  of  blood  infection  it  mav 
produce  endocarditis,  endarteritis,  or  thrombophlebitis.  Ordinarily 
in  pneumococcic  infection  a  prompt  leukocytosis  occurs ;  in  rapidly  fatal 

'  For  the  demonstration  of  capsules,  see  Capsule  Stains  in  chapter  on  Bac- 
teriologic  Technic. 

2  Its  action  on  these  structures  is  discussed  in  chapters  on  Diseases  of  the 
Mticous  Membranes  and  Diseases  of  the  Lunos. 


BACTERIA   AS  CAUSES  OF   DISEASE 


cases  there  may  he  no  leukocytic  response,  the  number  of  leukocytes 
rapidly  falling.  With  regard  to  the  yioisons  produced  by  the  jjneumu- 
coccus  much  remains  to  be  determined.  Its  short  life  on  cultivation  is 
not  conducive  to  the  production  of  toxins  in  suiVicient  (juantity  for  experi- 
mental investigation.  The  Klemperers  obtained  a  toxin  (pneumotoxin), 
anil  the  symptoms,  lesions,  and  complications  of  pneumonia  and  other 
pneumococcic  infections  indicate  that  its  action  is  exerted  through  the 
intervention  of  some  poison  which  it  produces.  Animals  can  be  im- 
munized against  the  ymeumococcus,  but  attempts  to  produce  immuniz- 
ing sera  have  been,  on  the  whole,  disappointing.  Stuertz  thought  that 
in  ])neumococcic  infections  information  as  to  prognosis  might  be  obtained 
bv  inoculating  animals.  By  using  the  sputum  he  found  that  in  virulent 
cases  of  pneumonia  mice  succumbed  in  from  six  to  eight  hours;  in  the 
more  chronic  cases  the  animals  sur- 
vived two  days. 

The  pneumococcus  is  also  the 
cause  of  chronic  inflammatory  con- 
ditions, either  catarrhal  or  pseudo- 
membranous, affecting  various 
mucosae,  but  particularly  the  nose 
and  bronchi.  Tizzoni  and  Panichi 
have  found  that  it  may  remain  latent 
in  the  circulation  for  weeks  or 
months. 

The  Meningococcus  or  Diplo- 
coccus  intracellularis  meningitidis' 
i^Weichselbaum.  1887)  ])OSsesses  al- 
most the  exact  morphology-  of  the 
gonococcus  and  is  also  commonly 
found  within  the  cells.  It  usually 
occurs  in  pairs  or  fours,  and  some- 
times in  short  chains  of  four  to  six 
elements.  It  is  non-motile,  aerobic, 
cultivated  with  difficulty,  and  has  a 
restricted  temperature  range  at  or 
near  37°  C.     It  grows  best  on  blood- 

'  See    foot-note.    p.     Si.       Council- 
man. Mallor>-,  and  Wright,    "Epidemic 


Fio.  63.-  Spt-tt'V.  ri?nriv>rs  Pvftmovta 

In  the  cxtrcii' 
ing  chn 
r<xci .      I 
is  a   mi. 
right  of  ■ 
niorphfiir. 
lower  pan.  oi 
The  field  .iLs<. 
pneumococii 
ranged    cocci    thui 
accuracy. 


jn  nul    hv  iiliniifn'.l   \m'! 


SchilY.  "Centralbl.  f.  inn.   Med.."  June  4.   1898;      al.so  Mandoul 

Feb.  II,  iQos,  p.  89.  and  Lord.    'Centralbl.  f.  Bakt.."  Oct.  9.  «903.  P-  ^4S 

ingococcus  in  Nose  in  Health  and  Disease."     Auch-V  ••Revue  Mens,  des  M; 

fance,"    Jan.,    1904,    '•Diplococcus    Meningitis 

'•Arch.  gen.  de  Med.  Exp.,"  1904.  So.  8,  p.  449- 

Berg.    "Med.    Record."   Sept.    10.    1904.    "New    1 

Reuling.  'Marvland  Med.  jour.,"  June,  1904,  cant  ul  stu<! 

titioner,"   Feb.'.    100^,  p.   217,   "Meningococcus  m  Infani:.- 

raphv.      Maradiano."  "Gaz.  Osped.  et  Clin.."  1905.   No.  19. 


al    IKii- 


Ri 
in  chrni 


.aph,.      ..-,........,..« --r^ —  -     -         .       ,-,  - 

duction    of    Meningitis    from    Nasal    Infection.        Nuttall    ai 
Med.   Jour.."   Sept.    21,    1901,  on   two  types  of  the  mening.A.v^ 
"Pediatrics."  Oct.  i>,  1900. 


vu.      i":i<.htr. 


112  GENERAL    PATHOLOGY. 

serum  or  on  Loffler's  medium,  on  both  of  which  it  produces  smooth, 
round,  colorless,  slightly  lustrous  colonies,  the  borders  of  which  are  usu- 
ally sharply  defined,  although  they  may  become  confiuent;  maximum 
development  occurs  in  six  days  and  transplantation  every  two  or  three 
days  is  necessary.  Growth  on  agar  is  scanty,  in  stroke  cultures  l)ut  two 
or  three  millimeters  in  width  the  surface  moist  and  not  granular.  It 
clouds  bouillon  with  the  formation  of  a  slightly  viscid  sediment.  It 
grows  feebly  or  not  at  all  on  gelatin  and  does  not  hquefy  the  medium. 

Demonstration. — It  stains  with  the  usual  anilm  dyes,  but  its  re- 
action to  Gram  is  inconstant.  For  this  and  other  reasons  Nuttall  and 
Hunter  concluded  there  were  two  types,  which  they  designated  "A" 
and  "B";  the  latter  is  Gram-positive,  grows  luxuriantly  on  agar,  pro- 
ducing viscid  colonies;  the  growth  on  potato  is  also  good.  Type  "A" 
is  indefinite,  visually  negative  to  Gram,  of  feeble  growth  on  agar  and 
glycerin-agar ;  there  is  a  slight  invisible  growth  on  potato.  For  staining 
sections  Councilman.  Mallory,  and  Wright  recommend  Unna's  alkaline 
methylene-blue  solutions  (see  p.  48)  applied  as  follows:  (i)  Saturated 
aqueous  solution  of  eosin.  twenty  minutes  or  longer;  (2) wash  in  water; 
(3)  alkaline  methylene-blue  (diluted),  one  or  two  hours;  (4)  wash  in 
water;  (5)  differentiate  in  commercial  alcohol  followed  bv  absolute 
alcohol;  (6)  clear  in  xylol ;  (7)  mount  in  balsam.  Spreads  may  be  treated 
in  the  same  way.  Cultures  are  usually  secured  from  fluid  obtained  bv 
lumbar  puncture,  and  while  the  fluid  so  obtained  may  appear,  bv  stain- 
ing methods,  to  contain  a  large  number  of  organisms,  culture  experi- 
ments indicate  that  comparatively  few  of  these  are  viable.  For  this 
reason  a  relatively  large  quantity  of  the  fluid  should  be  spread  over  the 
surface   of  the   culture-medium. 

Pathogenesis. — The  meningococcus  is  generally  admitted  to  be  the 
cause  of  epidemic  cerebrospinal  fever. ^  Still  has  recently  summarized 
the  reported  epidemics  of  infantile  paralysis  in  which  the  meningococcus 
was  found.  It  is  sometimes  present  in  sporadic  cases  of  meningitis 
and  infantile  paralysis.  It  probably  reaches  the  meninges  from  the 
nasal  passages,  in  which  it  is  occasionally  found  in  health,  but  more 
frequently  in  meningitis;  Maragliano  has  produced  meningitis  in  rabbits 
by  spraying  cultures  of  the  organism  into  the  nasal  cavity.  The  menin- 
gococcus is  feebly  pathogenic  for  mice,  rabbits,  guinea-pigs,  and  dogs. 

Meningitis  has  been  produced  in  the  goat  by  intracranial  inoculation. 
According  to  Lepierre,  it  produces  a  toxin  (meningotoxin)  which  resembles 
the  gonotoxin  studied  by  Christmas.  The  meningococcus  has  been 
found  in  endocarditis. 

The  Diplococcus  rheumaticus-  (Poynton  and  Paine)  occurs  as 
paired  cocci.  0.5  ,".  or  slightly  larger,  and  has  been  found  in  the  joint 
fluids,  synovial  membrane,  and  endocardial  lesions  of  acute  articular 
rheumatism.  It  grows  best  in  mixtures  of  bouillon  and  milk  faintlv 
acidified  Ijy  lactic  acid ;  it  can  also  be  cultivated  on  blood-smeared  agar 
and  blood-serum.  On  solid  media  the  colonies  are  small,  spherical,  and 
granular.  On  milk  it  produces  lactic  and  acetic  acids,  and  on  glucose 
and  levulose  media,  acetic  and  valerianic  acids.     Walker   and    Rvft'el 

'  See  chapter  on  Diseases  of  the  Xervous  System. 

^  Practically  all  existing  knowledge  concerning  this  organism  will  be  found 
in  or  may  be  traced  from  Poynton's  article  in  "The  Practitioner,"  July  1,  1904, 
p.  864.  See  also  Triboulet  and  Coyon.  "Rheumatisme  Articulaire  Aigite,"  1901, 
and  Beattie,  "Jour,  of  Path,  and  Bact.,"  March,  1904,  p.  272. 


HACTKklA    AS  CAl'SES   OF   DISFCASK.  1  I  < 

found  that  it  prodiKctl  forimc  atul  ami  was  slrcjiij^ly  liemolytic.  In 
li(iui(l  media  it  forms  short  chains,  on  l)lood  and  serum  agar  there 
IS  no  irregularity  in  its  arrangement.  The  organism  stains,  but  not  in- 
tensely, with  the  usual  anilin  dyes;  it  is  Gram-negative. 

Patlio'^cncsis. — In  rabbits  the  articular  and  cardiac  lesions  of  acute 
rheumatism  have  been  produced  by  intravenous  injections  of  the  organ- 
ism; non-suppurative  iritis  occasionally  occurs.  Poynton  has  shown 
that  monkeys  are  susceptil)le  to  the  organism.  It  is  identical  with  the 
Micrococcus  rheumaticus.  described  !iy  Walker  and  Beaston.  and  Was- 
sermann's  chorea  streptococcus. 

Pyogenic  Staphylococci.' — This  group  includes  a  number  of  micro- 
cocci, some  of  which  more  than  any  other  organism  are  ubiquitous. 
The  Micrococcus  pyogenes  aureus  occurs  singly,  in  pairs,  in  fours,  and 
in  short  chains,  most  commonly  in  irregular  masses.  It  is  a  non-motile, 
facultative  anaerobe,  measures  0.8  ,"•  to  i  /',  and  grows  readily  on  all 
laboratory  media  at  temperatures  lietween  20°  C.  and  40°  C.  the  oj)- 
timum  being  30°  C.  to  37*^  C;  it  is  killed  by  exposure  for  half  an  hour 
at  So°  C.  In  gelatin  the  growth  is  rapid  and  the  medium  liquefied; 
a  faint  white  streak  appears  along  the  line  of  puncture,  the  growth 
gradually,  by  the  third  day.  assuming  a  deep  yellow 
or  golden  hue.  The  organisms  fall  to  the  bottom 
of    the    liquefied    medium,    forming    a    deep    yellow  _..•;•.. 

sediment.      Stroke  cultures  on  agar  develop  as  thin.  '^:*^<>'' 

white,  slightly  yellowish,  opaque  films,  irregular  in  ^J^"^ 

outline.     The    characterist  c    yellow    color    appears 
by    the    third   day.      The    agar   frequently    becomes      n...  64 -microcoiws. 
cloudy  and  opaque,  but  does  not  liquefy.     On  solidi-  PY'».*NKs'°l{^lii(s! 

hed   serum  essentially    the   same   characteristics  are  u  opiin  and  Br- 

developed.     On    potato    the    culture   is   white,   later  ;.','".         °°   """' 

taking  on   a   yellow   color,   and   with   age    becoming 
succulent  and  yielding  a  sour  odor.     On  plates  the 
growth  appears  within  twenty-four  to  thirty-six  hours,  as  slightly  elevated 
white  colonies  with  sharply  defined  edges;   gradually  the  golden-yellow 
color  develops.      It  renders  bouillon  turbid,  depositing  as  a  brownish- 
yellow  sediment.   It  stains  by  the  usual  anilin  dyes  and  by  Gram's  method. 

The  Micrococcus  pyogenes  citreus  in  every  respect  resembles  the 
aureus  excei)t  that  ii  dcxclojis  a  lemon  yellow  color.  The  Micrococcus 
pyogenes  albus  has  essentially  the  same  characteristics  excei)t  that  its 
growth  i>  <1(  AVer  and  the  colonies  are  milk  white  in  color.  The  Staphylo- 
coccus epidermidis  albus  is  i)robably  a  strain  of  the  preceding  organism. 
The  Micrococcus  cereus  albus  is  slightly  larger,  the  colonies  are  small 
and  white,  wax-like,  and  it  does  not  liquefy  gelatin.  The  Micrococcus 
cereus  flavus  is  a  similar  organism  except  that  it  develops  a  yellow 
pigment. 

The  pyogenic  or  pus-i)roducing  staphylococci  stain  by  practically 
allot  the  laboratory  methods  and  are  positive  to  Gram.  The  Micro- 
coccus pvogenes  aureus  is  the  organism  most  commonly  found  in  sup- 
purative processes.     Curry-  found  it  in  52  of   115   abscesses;   the  albus 

'  The  ttrtTi  staphylococcus  is  much  used,  particularly  by  surgeons,  instead 
of  micrococcus.  The  studt-nt  should  remember  that  the  terms  are  interchanpe- 
able.      For  references  see  page  81. 

'  "Medical  and  Surjrical  Reports  of  the  Boston  CitV  Hospital."  1S07 


114  GEXERAL    PATHOLOGY. 

was  present  in  29.  The  aureus  was  the  only  organism  present  in  32. 
The  tact  that  this  organism  is  constantly  present  on  the  surface  of  the 
body  and  on  the  mucous  membranes  accounts  for  the  frequency  with 
which  it  is  found  in  surgical  infections.  The  pathogenicity  of  the 
different  members  of  the  group  varies,  nor  is  it  always  the  same  for 
any  one  of  the  staphylococci.  It  has  been  demonstrated  that  there 
are  saprophytic  staphylococci,  and  it  is  probable  that  these  are  atten- 
uated forms  of  the  pathogenic.  Xeisser  and  Vechsberg  have  shown 
that  pathogenic  staphylococci  produce  hemolysins  and  leiikocidins,  while 
the  saprophytic  do  not.  Klopstock  and  Bockenheimer  have  found 
that  animals  immunized  to  pathogenic  staphylococci  produce  sera 
agglutinating  these  organisms  but  not  the  saprophytic  form. 

The  most  characteristic  features  of  the  staphylococci  are  their 
intense  positive  chemiotactic  action  on  leukocytes,  particularly  the 
polymorphonuclear.  Cultures  of  the  aureus  sterilized  by  boiling  may, 
when  introduced  subcutaneously,  cause  abscesses;  if  heated  to  120°  C. 
in  the  autoclave,  this  property  is  lost.  Christmas  has  been  able  to  isolate 
from  filtered  bouillon  cultures  a  pyogenous  substance  to  which  he 
attributes  the  pus-producing  faculty  of  the  aureus.  Introduced  into 
the  circulation  in  sufficient  numbers  the  pyogenic  staphylococci  may 
give  rise  to  septicemia  or  pyemia.  There  is  abundant  evidence  to 
show  that  in  animals,  and  probably  in  man,  these  bacteria  are  fre- 
quently present  in  the  circulating  fluid;  ordinarily  the  number  is  small 
and  conditions  are  unfavorable  for  colonization.  The  occurrence  of  an 
injury,  which  may  be  trifling  in  extent,  develops  a  point  of  lessened 
resistance  in  which  the  organism  may  develop.  In  addition  to  the 
ordinary  suppurative  lesions  caused  by  staphylococci,  they  may  be 
found  in  osteomyelitis,  endocarditis,  cellulitis,  in  the  pustules  of  acne 
and  smallpox,  and  in  the  throat  lesions  of  scarlet  fever  and  diphtheria. 
When  present  as  concurrent  infections,  absorption  of  the  products  of 
the  pyogenic  organism  intensifies  the  lesions  and  symptoms  due  to 
the  disease  with  which  they  are  associated. 

The  Streptococcus  pyogenes^  (Rosenbach,  1S80)  is  a  non-motile, 
aerobic,  pus-producing,  chain-forming  coccus,  0.4  ,".  to  i  /'.  in  diameter: 
its  optimum  temperature  is  35°  C.  to  37°  C.  It  does  not  grow  well 
below  25°  C.  to  30°  C.  and  is  extremely  susceptible  to  even  slight  eleva- 
tions, being  killed  in  ten  minutes  at  52°  C.  On  gelatin  plates  it  gives 
rise  to  small,  circular,  finely  granular  colonies,  which  when  fully  devel- 

'  See  foot-note,  p.  81.  Discussion  before  the  Med.  Soc.  of  London. 
Jan.  II,  1904.  Ruediger,  "Jour.  Amer.  Med.  Assoc,"  Oct.  17,  1903,  "The  Pro- 
duction and  Nature  of  Streptocolysins,"  with  bibliography;  also  "Jour.  Amer. 
Med.  Assoc,"  Jan.  21,  1905,  "Mechanism  of  Streptococcus  Infection."  Pe- 
truschky,  "Zeit.  f.  Hyg.  u.  Infek.,"  xxiii,  No.  i,  "Nonspecific  Character  of  the 
Erysipelas  Streptococcus."  Bulloch,  "Trans,  of  Brit.  Inst,  of  Preventive 
Med.,"  ist  series.  Bergey,  "Penna.  Med.  Jour.,"  Nov.,  1903,  p.  71,  "Strepto- 
cocci and  Antistreptococci  Sera";  bibliography.  Weaver,  "Jour,  of  Med.  Re- 
search," May,  1903,  "Streptococci,  Especially  in  Scarlatina";  also  "Trans.  Chicago 
Path.  Soc,"  Feb.  9,  1903.  Hektoen,  "Jour.  Amer.  Med.  Assoc,"  March  14. 
1903,  on  "Streptococcemia  in  Scarlet  Fever."  De  Wale  and  Sugg,  "Arch.  Intern  . 
Pharmacodyn.  et  Therap.,"  vol.  12,  fasc.  3  and  4,  1903,  p.  205,  "Streptococcus 
in  Variola."  Zelenski,  "Wien.  klin.  Woch.,"  April  14,  1904,  "Agglutination  of 
Streptococci."  Schamberg  and  Gildersleeve.  "Medicine,"  Sept.,  1904,  "Strep- 
tococci and  other  Organisms  in  the  Throat  in  Scarlet  Fever."  The  principal  facts 
with   regard   to   agglutination   of  streptococci   may  be   obtained   from   Weaver, 


r.  Ai    ll.KIA    AS   CATSICS  <tr    DISKASK 


"5 


oped  are  light  hrown,  often  extending  from  the  margins  irregular, 
serj)entine  filaments;  gelatin  not  li(iuefie<i.  On  bouillon  some  strep- 
tococci grow  much  better  than  others.  One  strain  of  the  organism 
may  produce  cloudiness  without  film  or  se<liment,  others  give  rise  to 
a  pellicle  which,  after  formation,  settles  to  the  bottom.  Most  strepto- 
cocci form  acids.  On  agar  small,  whitish,  slightly  elevated  colonies 
I  mm.  to  2  mm.  in  diameter  develop;  they  may  become  confluent. 
The  streptococcus  frequently  coagulates  milk/.sometimes  rapidly,  often 
slowly,  and  occasionally  not  at  all. 

DcnuvL^tration. — The  streptococci  stain  readily  with  mo.st  anilin 
dyes.  The  different  cocci  in  the  same  chain  do  not  all  stain  with  the 
same  intensity  nor  are  they  all  the  same  size.  It  is  practically  always 
Gram-positive;  Etienne  has  obtained  from  the  false  membranes  in 
angina  a  streptococcus  that  does  not  take  the  Gram  stain,  and  Lemoine 
has  found  a  similar  organism  in  erysipelas;  the  reaction  to  Gram  may 
be  modified  by  cultivation.  Vandevella  studied  twentv  strains  of 
streptococci,  many  of  which  were  dissimilar,  although  he  regarded  them 
as  being  members  of  the  same  group.  Foulerton  investigated  twenty- 
five  strains  and  believes  there  is  more  than  one  dis- 
tinct species. 

Pathogoicsis. — The  virulence  of  streptococci  varies 
widely.     It    may   be   increased   by   passage  through  \. 

animals  and  diminished  by  cultivation.    Cultures  pre-  \  ':\   ..••• 

served  under  conditions  that  exclude  oxygen  retain  '**.V-^1§*0- 

their  virulence.     Various  cytolytic  poisons  are  pro-  ****-..  **v^' 

duced  by  the  streptococcus;    the  most  important  of 
these  attack  the  red  blood-cells  (erythrocidins) -and      i-i,-..    65.— stbeptot.k- 
leukocytes   (leukocidins).    Sterile  cultures  may  con-  —fcVpi^^lVJ^B^^ 

tain  poisons  sufficiently  active  to  kill  small  animals.  <>»■)   x   800  di»m- 

and  it  seems  reasonable  to  conclude  that  the  symp-  '"'"^ 

toms  of   streptococcus   infection  in  man  are   due  trj 
the  intracellular  and   extracellular  toxins  produced  by  the  organism. 
The  serum  of  animals  immunized  to  the  streptococcus  contains,  among 
other   substances,  agglutinins   which   may   Ije   utilized   for   identifving 
the  organism. 

Streptococci  have  been  found  in  a  large  number  of  morbid  processes, 
among  which  especially  should  be  mentioned  suppurative  lesions,  erv- 
sipelas,    peritonitis,    pericarditis,    pleurisy,    meningitis,    and    arthritis; 

■  Jour,  of  Infectious  Diseases,"  1904.  vol.  iv.  j>.  01.  Cole.  "Jour,  of  Infectious 
Disease."  Nov.  5.  1904,  p.  714.  "Experimental  Streptococcus  Arthritis  and  its 
Relation  to  Acute  Rheumatism."  Foulerton.  "Lancet."  Dec.  31.  1904,  p.  i8iS. 
Hiss,  "Jour,  of  Exper.  Med.,"  vol.  vi,  p.  317,  "Differentiation  of  Pneunioc<X'cu.s 
and  Streptococcus."  Simon,  "Centralbl.  f.  Bakt.."  HJ03.  xxiv,  al.so  Vaiiijhan. 
"The  Phvsician  and  Surgeon,"  May,  1904.  "The  Strept(x:occus  Toxt"  ^'die- 
singer.  "2eit.  f.  Hyg.  u.  Infcctk.."  1903.  Bd.  xliv,  p.  428.  "Strept<  ■  110- 
Ivsins."  Neumann.  "Centralbl.  f.  Bakt.."  xxxvii.  1904.  p.  381."  1.  ted 
Pathogenic  Streptococci."  Fischer.  Ibid.,  p.  449.  "Agglutination  of  rail»..i;enic 
and  Saprophytic  Streptococci."  Discussion  on  Antistreptococcic  Serum  th>r- 
apy  before  the  Berlin  Med.  Society,  Feb.  Sand  15.  1905.  re|)orted  in  March 
01  the  "Berl.  klin.  Woch,"  also  "LaScmaine  .Mrfl. "  March  i,  1005.  I 
"Trans.  Chicagt)  Path.  Six:.."  vol.  vi,  "Stnpt<x-ot-ci  on  Normal  Tonsils  >.  ■.  i- 
regard  to  treatment  by  antistrept<>coci  ic  serum  consult  the  followmc;;  Aver. 
"Med.  Reconl."  March  4.  1905.  Hamilton  '.Xim  r.  I-nr  -if  ()l)«;t.t  "  Nov 
n>04.      Peham,  "Arch.  f.  Gvnek.,"  Bd.  Ixxi 


H6  GEXERAL    PATHOLOGY. 

certain  strains  of  the  organism  produce  a  highly  virulent  puerperal  fever. 
The  streptococcus  found  in  erysipelas  possesses  no  constant  character- 
istics by  which  it  may  be  differentiated  from  some  strains  of  pyogenic 
streptococci,  and  it  has  been  shown  by  a  number  of  observers  that, 
using  the  same  chain-forming  coccus,  cuticular  inoculation  gives  rise  to 
ervsipelas  and  subcutaneous  injection  causes  abscess  formation. 

The  relation  of  streptococci  to  scarlet  fever  has  been  studied  recently 
bv  a  number  of  observers,  the  consensus  of  opinion  being  that  it  is  not 
the  cause  of  the  disease.  The  lowered  vital  resistance  of  patients  hav- 
ing scarlet  fever  and  diphtheria  favors  colonization  of  pathogenic  strep- 
tococci primarily  in  the  pharyngeal  lesions,  from  w^hich  the  poisons  pro- 
duced by  the  organism  may  "be  absorbed,  or  the  germ,  entering  the  cir- 
culation, may  further  embarrass  the  already  heavily  taxed  protective 
powers  of  the  patient,  causing  a  fatal  issue.  Whether  the  poisons  of  the 
streptococcus  be  absorbed  from  a  local  lesion  or  produced  in  the  circulat- 
ing blood  (streptococcemia),  they  exert  a  powerful  action  on  the  tissues. 
Degenerative  or  necrotic  changes  occur  in  the  muscles,  particularly  the 
heart,  and  also  in  glandular  viscera,  especially  the  liver  and  kidneys. 
The  spleen  enlarges  and  contains  areas  of  necrosis;  prohferative  activity 
is  manifested  by  the  bone-marrow,  m  which  necrotic  processes  may 
also  develop.  Degenerative,  or  rather  toxic,  manifestations  have  been 
noted  in  the  central  nervous  system.  Should  the  streptococcus  colonize, 
abscess  formation  (streptococcic  pyemia)  occurs.  A  highly  virulent 
type  of  endocarditis  is  sometimes  produced  by  this  organism.  ^  Local- 
ized on  the  intima  of  the  arteries  or  veins  the  streptococcus  produces 
septic  thromboarteritis  or  thrombophlebitis,  which  may  extend  for  a 
considerable  distance  along  the  course  of  the  affected  vessel ;  in  this  way 
the  thrombosing  phlebitis  and  lymphangitis  (milk  leg)  of  puerperal  sepsis 
may  be  produced.  The  studies  of  Hasenknopf  and  Salge-  and  Neufeld^ 
indicate  that  while  agglutination  tests  may  be  of  value  in  the  identi- 
fication of  streptococcal  infections,  the  variability  of  sera  and  the  ag- 
glutinability  of  various  strains  of  streptococci  render  it  difficult  to  esti- 
mate in  any  given  case  the  trustworthiness  of  the  results  obtained.  The 
sera  of  animals  immunized  to  the  streptococcus  have  been  used  in  the 
treatment  of  streptococcal  infections ;  it  has  been  established  that  such 
sera  possess  protective  powers  and  may  be  of  value.  Serum  obtained  from 
an  animal  immunized  against  a  single  strain  of  streptococci  (monovalent 
serum)  is  very  much  less  efficacious  than  that  obtained  from  animals  im- 
munized to  a  number  of  strains  (polyvalent  serum);  the  latter  has  been 
found  useful  in  such  streptococcic  infections  as  erysipelas  and  strepto- 
coccemia, especially  that  occurring  in  puerperal  sepsis.  It  is  probable 
that  the  usefulness  of  these  sera  depends,  in  part  at  least,  on  the  presence 
of  antistreptocolysins. 

The  Micrococcus  melitensis^  (Bruce,  1887)  is  a  round  or  slightly 
oval  coccus,  about  0.33  p.  to  0.5  ;>.  in  diameter,  sometimes  arranged  as 

'  See  Endocarditis  in  chapter  on  Diseases  of  the  Vascular  System. 

^  "'Jahrb.  f.  Kinderheilk.,"  1903,  vol.  Iviii. 

'  "Zeit.  f.  Hyg.,"  1903,  vol.  xliv. 

*  See  works  referred  to  in  foot-note,  page  81.  Sandwith.  'Practitioner,' 
June,  1904,  p.  791.  Carbone,  "Arch,  di  scienze  mcd.,"  1904,  2e  fasc,  p.  273. 
Allen,  "Jour,  of  Royal  Army  Med.  Corps,"  1904,  p.  699:  the  latter  volume  con- 
tains a  number  of  references  to  this  organism.  Allbutt's  "System  of  Medicine." 
vol.  ii,  p.  463. 


BACTKRIA    AS   CAUSES   OF    DISKASK.  II7 

diplococci.  rarely  forming  short  chains,  and  usually  thought  to  he  non- 
motile;  with  regard  to  the  motility  authorities  are  not  agreed.  In 
cultures  occasionally  one  diameter  of  some  of  the  organisms  increases, 
givmg  rise  to  bacillary  forms.  It  slowly  clouds  bouillon,  eventually 
forming  a  deposit  but  no  surface  film.  Agar  containing  0.5  per  cent, 
peptone  is  the  best  medmm :  stroke  cultures  on  the  surface  give  rise 
to  small,  whitish,  slowly  enlarging  colonies  2  mm.  to  3  mm.  m  diameter 
and  more  opaque  at  the  center  than  at  the  periphery,  which  may  be 
serrated.  There  is  a  slowly  developing,  scant v  growth  on  gelatin, 
but  the  medium  is  not  lirjuefied. 

Ik'nioiistratioii. — The  organism  is  obtained  in  culture  bv  inocula- 
tions made  from  the  spleen.  It  stains  with  the  usual  anilin  dyes,  but  is 
Gram-negative;  neither  films  nor  spreads  bear  alcohol  differentiation. 

PatliOi^oicsis. — The  disease  prociuced  in  man  by  the  Micrococcus 
melitensis  is  called  Malta  fever.  The  ordinary  laboratory  animals  are 
refractory,  but  the  affection  has  been  produced  in  monkeys,  in  which 
it  runs  a  typical  course.  In  man  the  spleen  is  greatly  enlarged,  soft  and 
friable;  the  incised  surface  is  dark,  intensely  congested,  and  the  sinuses 
enormously  distended  with  blood.  The  organism  can  readily  be  demon- 
strated in  the  softened  splenic  pulf).  The  liver  is  swollen,  dark  in  color, 
with  more  or  less  conspicuous  interloV)ular  round-cell  infiltration.  The 
kidneys  are  congested,  the  capsules  easily  detached,  and  there  may  be 
subcapsular  and  interstitial  hemorrhages.  The  large  intestine  is  often 
congested  and  the  mesenteric  glands  may  be  slightly  enlarged.  Ulcera- 
tions do  not  occur.  The  disease  is  of  variable  duration,  sometimes  lasting 
several  weeks;  Bruce  state-,  that  the  mortality  is  about  two  per  cent. 
It  has  generally  been  thought  that  infection  occurs  by  the  alimentary 
canal.  Allen  thinks  it  will  eventually  be  shown  that  Malta  fever  is 
disseminated  by  soms  insect. 

Ai^i^liitiiiatioii  mav  be  of  some  value  in  diagnosis,  although  the  dilu- 
tion necessarv  nia\'  be  an\\vhere  between  i  in  10  and  i  in  1000.' 

The  Micrococcus  tetragenus-  is  a  non-motile,  facultative  aerobe, 
0.6  ,"  to  I  /'  in  diameter,  occasionally  found  in  groups  of  two.  usually 
four,  and,  in  the  body  fluids  and  tissues,  often  appears  encapsulateci. 
On  gelatin  plates  it  gives  rise  to  small,  white,  finely  granular  colonies 
having  a  vitreous  luster;  it  grows  well  on  agar,  potato,  and  blood-serum, 
forming  a  heavy  white  surface  colony.  The  growth  is  at  first  slow,  but 
after  from  fortv-eight  to  seventy-two  hours  more  rapid.  Does  not 
licjuefy  gelatin. 

Pciuoustratio)!. — The  tetracoccus  stains  by  the  usual  anilin  dyes 
and  by  Gram's  method. 

Pathojioicsis. — It  may  be  made  to  infect  mice  and  guinea-pigs,  but 
in  man  it  appears  to  be  largely  a  saprophyte.  It  has  been  found  alone  in 
abscesses,  particularly  around  the  teeth.  Usually  it  is  encountered  in 
sputum  and  tuberculous  cavities  and  has  been  observed  with  the  pneumo- 
coccus  in  the  pus  of  empyema  and  meningitis.  A  tetracoccemia  can  be 
produced  in  animals,  but  it  is  doubtful  if  the  organism  ever  so  affects 
man. 

'  For  method  of  aRglutination,  .sec  chapter  on  Bacteriologic  Tcchni*- 
'  Sec  works  rcfcrrcii  t<>  in  foot-note,  p.  Si. 


Il8  GEXERAL    PATHOLOGY. 

The  Bacillus  diphtheriae '  (Klcbs,  1883;  Loffler,  1884)  is  a  straight 
or  slightly  curved  rod.  extremely  pleomorphous,  measuring  2  ,".  to 
4.8  !>■  in  length  and  0.3  ,".  to  i  ,".  in  breadth;  branched,  granular,  barred, 
and  other  irregular  forms  occur.  The  organism  is  a  non-motile  aerobe 
and  facultative  anaerobe,  optimum  temperature  37°  C,  minimum 
18°  C,  and  does  not  grow  above  42°  C.  Vitality  may  be  preserved 
for  about  a  year.  It  grows  best  on  Lofifler's  blood-serum  mixture, 
on  which  colonies  are  visible  in  twenty -four  hours,  as  small,  grayish, 
opaque  dotlets,  easily  extended  by  any  overflowing  water  of  condensa- 
tion. In  gelatin  stab  cultures,  small  whitish  or  grayish-white  dots 
develop  along  the  needle  track,  while  on  the  surface  the  puncture  is 
surrounded  by  a  growth  somewhat  thicker  in  the  middle ;  the  medium 
does  not  liquefy.  Growth  on  agar  resembles  that  on  serum ;  the  growth 
on  potato  is  at  first  invisible  and  may  develop  a  thin,  grayish  glaze. 
Spore  formation  is  not  believed  to  occur.  Grown  in  bouillon  contain- 
ing glucose  the  medium  at  first  becomes  acid  and  later  alkaline  in 
reaction. 

Demonstration. — Swabs  are  prepared  by  firmly  wrapping  one  end 
of  a  piece  of  wire  (fourteen  centimeters  long  and  about  two  millimeters 
in  thickness)  with  cotton,  which  should  completely  cover  the  end,  so 
as  to  prevent  possible  injury  when  the  swab  is  applied.  Ten  centi- 
meters from  the  same  end  a  second  roll  of  cotton  is  placed  around 
the  wire,  sufficiently  large  to  fit  tightly  into  the  mouth  of  a  test-tube. 
The  swab  and  test-tube  are  sterilized  in  a  hot-air  sterilizer.  The  in- 
oculations are  obtained  by  rubbing  this  swab  over  the  affected  area 
and  then  at  once  gently  smearing  the  surface  of  a  slant  tube  of  Loffler's 

^  See  works  referred  to  in  foot-note  on  p.  Si.  For  recent  literattire 
on  the  toxins  see  Ehrlich,  "Berl.  klin.  Woch.,"  1903;  Calcar,  "Berl.  klin. 
Woch.,"  Sept.  26,  1904,  p.  1028;  Arrhenius  and  Madsen,  "Centralbl.  f. 
Bakt.,"  1904,  vol.  xxxvi;  Schwoner,  "Centralbl.  f.  Bakt.,"  Bd.  35;  Si- 
mon, "Arch,  de  Med.  Exp.  et  d'Anat.  Path.,"  Nov.,  1903,  p.  763;  Rist, 
"Soc.  de  Biol.,"  July  11,  1903;  Pick  and  Schwoner,  "Wien.  klin.  Woch.." 
Oct.,  1904,  p.  1065;  Theobald  Smith,  "Jour,  of  Med.  Research,"  vol. 
xiii.  No.  3,  p.  341.  For  recent  studies  on  the  toxic  action  of  the  diphtheria 
bacillus  see  Rist,  "Rev.  mens,  de  I'Enfance,"  Sept.,  1904,  the  "Pathogenesis  of 
Diphtheritic  Paralysis."  Rolleston,  "Practitioner,"  Nov.,  1904,  p.  597,  "Clinical 
Observations   on    Diphtheritic    Paralysis."      Babonneux,    These    de    Med.    Paris, 

1904,  "Experimental     Diphtheritic     Paralysis."      Bolton,     "Lancet,"     Feb.     4, 

1905,  p.  278,  "Diphtheritic  Toxemia."     Hayem,  "Soc.  Med.  des  Hop.,"  Feb.,  1903, 
"Gastric   Lesions   Produced   by   Diphtheria  Toxin."      Graham-Smith,    "Jour,   of 

Hyg.,"  1904,  "Virvdence  of  Diphtheria  Bacilli,"  exhaustive  study  with  bibliog- 
raphy. Spirig,  "Zeit  f.  Hyg.,"  vol.  42,  p.  420,  careful  study  of  bacillus.  Kleiii, 
"Centralbl.  f.  Bakt.,"  vol.  xxxiii,  p.  488,  a  new  member  of  the  diphtheria  group. 
Laird,  "Albany  Med.  Annals,"  May,  1903,  p.  352;  "Pediatrics,"  Sept.,  1903, 
p.  532,  "Different  Forms  of  Diphtheria  Bacilli."  Newman  ("The  Practitioner," 
Nov.,  1903),  very  full  review  of  the  bacteriologic  diagnosis  of  diphtheria. 
The  bibliography  is  given  to  date.  Abbott  and  Gildersleeve,  "Centralbl. 
f.  Bakt.,"  Dec.  18,  1903,  p.  273,  "  Branching  Forms  of  the  Bacilkis." 
Andrade,  "Med.  News,"  Dec,  3,  1904,  p.  268,  review  of  groups.  Concetti,  "Ann. 
d'lgiene  sper.,"  vol.  xi,  "Actinomyces  Forms  of  the  Diphtheria  Bacillus."  Blu- 
menthal  and  Lipskerow,  "Centralbl.  f.  Bakt.,"  March  11,  1905,  "Differential 
Staining  Methods."  Knapp,  "Jour,  of  Med.  Research,"  Nov.,  1904,  "Identifica- 
tion of  the  Bacillus."  Hamilton,  "Jour,  of  Infect.  Diseases,"  vol.  i,  1904,  "Viru- 
lence of  So-called  Pseudodiphtheria  Bacilli."  See  also  Nothnagel's  "Encyclo- 
pedia of  Practice  of  Medicine,"  American  edition,  "Diphtheria,  Measles,  Scar- 
let Fever,  Rotheln."  Rover,  "Proceed.  County  Med.  Soc,"  Feb.  28,  1904. 
"Antitoxin  Treatment."  "Public  Health,"  June  8,  1903,  discussion  of  methods  of 
dissemination. 


HACTKkl  A   AS  CAUSES  OF   DISEASE,  IIQ 

medium.  Spreads  may  also  be  made  from  the  swab  on  cover-glasses 
and  may  be  fixed  in  the  usual  manner.  Colonies  on  Lofflcr's  mcflium 
appear  within  twenty-four  hours.  They  are  grayish  in  tolor.  moist, 
round  or  oval  in  outline,  slightly  more  elevated  ancl  o])a()ue  at  the 
center.  Spreads  from  such  colonies,  stained  with  L()ffler's  methylene- 
blue,  will  show  the  organism  as  previously  descriljed;  also  as  club- 
shaped  and  irregular  rods.  These  so-called  involution  forms,  staining 
irregularly,  are  of  great  diagnostic  value,  although  not  ])athognomonic. 
Sometimes  examination  of  spreads  from  the  moist  swab  yields  data 
corroborative  of  the  clinical  diagnosis;  if  the  cotton  is  moistened  with 
sterile  glucose  bouillon  and  the  swab  and  test-tube  incubaterl.  bacilli 
may  be  found  in  demonstrable  numbers  before  the  serum  culture  is 
productive.  Ohlmacher  found  that  bacilli  may  be  demonstrable  on 
the  medmm  some  hours  before  colonies  are  visible  macroscopically. 
He  recommends  that  after  four  hours'  incubation  spreads  be  made 
and  stained  by  the  usual  methods.  Invisible  growths  may  be  present 
after  eighteen  hours  at  room-temperature. 

Xcisscr's  Difjcrcntiating  Stain. — Dissolve  0.5  gm.  of  methylene-blue 
(Griibler)  in  10  c.c.  of  commercial  alcohol;  add  to  this  425  c.c.  of  dis- 
tilled water  and  25  c.c.  of  glacial  acetic  acid;  stain  cover-glass  ]>repara- 
tions  for  from  one  to  five  seconds;  wash  in  water,  and  stain  for  five 
seconds  in  solution  made  by  dissolving  0.5  gm.  of  vesuvin  in  350  c.c. 
of  boiling  distilled  water;  wash  in  water,  dry,  and  mount.  This  method 
shows  to  advantage  the  polar  granules  (metachromatic  granules)  in 
the  diphtheria  bacillus;  organisms  without  polar  granules  are  not 
those  of  diphtheria.  The  bacilli  of  pseudodiphtheria  may,  rarely, 
show  polar  granules. 

The  pathogenicity  of  the  organism  may  be  tested  by  subcutaneous 
injection  of  0.5  c.c.  of  bouillon  culture  from  twenty-four  to  forty-eight 
hours  old.     This  should  kill  a  medium-sized  guinea-pig. 

Pathogenesis. — The  virulence  of  the  organism  varies  within  wide 
limits,  is  rarely  the  same  for  any  two  cultures,  and  is  most  marked 
in  young  growi;hs;  during  cultivation  it  is  lost  more  quickly  on  agar 
than  on  serum  or  in  bouillon.  Occasionally  attenuated  and  non-virulent 
forms  can  be  made  to  reacquire  virulence.  Roux  and  Yersin  have 
shown  that  the  non-virulent  organism  is  rendered  more  active  by  con- 
current infection  with  the  streptococcus — an  association  frequently 
observed  in  diphtheria.  Inoculated  on  the  mucous  membrane,  catarrhal, 
pseudomembranous,  or  gangrenous  inflammation  ensues,  with  more 
or  le.ss  systemic  intoxication.  The  local  lesions  vary  widely  in  extent, 
and  are  sometimes  acute  and  fulminating;  Xeufeld '  states  that  the 
chronic  may  follow  the  acute  or  that  a  local  lesion  may  be  chronic 
from  the  beginning  and  can  persist  for  months  or  even  yr  t^  Tb.- 
bacillus  may  be  present  during  long  periods. 

The  organism  enters  the  blood  in  a  considerable  peri nii.ii;-  ■■! 
cases.  It  is  frequently  found  in  the  lungs  postmortem,  and  may  be 
the  only  organism  ])resent  in  the  associated  pneumonia.  It  has  been 
found  in  endocarditis  and  may  be  excreted  in  the  urine.  The  surface 
lesions  of  diphtheria  usually  occur  in  the  throat  or  nose:  in  the  larynx 
(larvngeal  diphtheria)  pseudomembrane  formation  may  occlude  the 
passage.  Diphtheria  of  the  esophagus  and  stomach  is  rare;  the  con- 
'  "Deut.  med.  W'-< '^     '  ^'  "    '  '    1004. 


GEXERAL   PATHOLOGY. 


junctiva.  external  genitals,  and  anal  margin  may  be  attacked.     Blis- 
tered surfaces  are  sometimes  infected  by  the  diphtheria  bacillus. 

Clinical  and  experimental  studies  clearly  establish  that  the  diphtheria 
bacillus  produces  all  its  manifestations  through  the  activity  of  the 
poisons  which  it  elaborates.  Often  death  appears  to  be  due  to  the  tox- 
emia alone.  Recent  studies  seem  to  indicate  that  in  order  to  explain 
the  clinical  and  pathologic  phenomena  of  diphtheria  it  is  necessary 
to  recognize  at  least  three  toxic  elements.  The  most  active  of  these 
is  the  extracellular  poison,  easily  obtained  from  cultures,  and  to  the 
action  of  which  must  be  attributed  granular  and  fatty  changes  in  the 
muscles,  particularly  of  the  heart,  and  the  degenerative  and  necrotic 
lesions  affecting  the  other  viscera,  especially  the  liver,  spleen, 
and  kidneys.  In  the  liver  more  or  less  cloudy  swelling  and 
multiple  areas  of  coagulation  necrosis  may  be  found.  The  renal  le- 
sions   differ  widely,  and   in   the  severer  forms  may  in  part  be  due  to 

concurrent  streptococcal 
infection.  In  the  milder 
cases  there  is  considerable 
granular  change  in  the 
tubular  epithelium,  which 
may  undergo  necrosis  and 
be  cast  off.  An  acute 
diffuse  nephritis  is  not  in- 
frequently present,  espe- 
cially in  fatal  cases;  with 
associated  streptococcus 
infection  minute  abscesses 
(acute  suppurative  neph- 
ritis) may  be  found.  The 
spleen  is  enlarged,  the  pulp 
soft  and  friable,  there  is 
more  or  less  endothelial 
proliferation  and  evidences 
of  hemolysis ;  areas  of  focal 
necrosis  are  practically 
always  present. 

Welch  and  Flexner 
have  shown  that  the  local  lesions  of  diphtheria  are  probably  due 
to  an  intracellular  toxin  (endotoxin).  Schwoner  has  demonstrated 
that  the  diphtheria  bacillus  produces  a  hernolytic  toxin  (diphtherioly- 
sin)  which  acts  principally  on  the  red  blood-cells.  Babonneux,  in 
animals,  has  succeeded  in  producing  a  localized  paralysis  restricted 
to  the  region  of  the  inoculation,  not  generalizing,  often  ending  in 
recovery,  and  in  other  ways  resembling  the  diphtheritic  paralysis 
occurring  late  in,  or  coming  on  after,  diphtheria  of  man.  Rolleston, 
Bolton,  and  others  are  of  the  opinion  that  the  diphtheritic  paralysis 
in  man  is  due  to  some  endotoxin.  The  fact  that  the  antitoxin  treat- 
ment of  diphtheria  has  greatly  reduced  the  mortality,  but  not  materially 
influenced  the  occurrence  of  paralysis,  speaks  in  favor  of  this  view. 
It  is  argued  that  the  prevailing  method  of  inducing  immunity  in  horses, 
by  the  use  of  filtered  cultures,  affords  an  antitoxin  for  the  extracellular 
poisons  but  offers  no  protection  from  the  intracellular  toxin  (endotoxin). 


Fig.   66. — Margin  of  Membrank   from  Tonsil,   Case  of 
Diphtheria. 
A,    A.    Diphtheria    bacilli;     the    pointer   from    the  lower    .-I   ends 
in    an    area    of   granular    material.    B    Cocci.     C,   Strands   of 
fibrin.     The  cellular  elements  present  are  squamous  epithelium, 
and  polymorphonuclear  and  hyaline  leukocytes. 


HAITKRIA    AS  CAUSKS  ()K    DISK  ASK. 


I  21 


It  is  also  possible  that  the  diphtheritic  j)aralysis  may  he  <luc  to  some 
poison  resemblinj^  or  related  to  the  toxone  described  by  Khrlich.  Bolton 
partioularlv  adheres  to  the  belief  that  affections  of  the  peripheral  nerves 
are  due  to  the  action  of  a  toxone. 

Diphtheria  Antitoxin.'— The  antitoxic  treatment  ol  dij)hthena  is 
one  of  the  most  brilliant  achievements  that  has  followed  the  laboratory 
study  of  disease.  Repeated  administration  of  diphtheria  toxin  gives 
rise  to  powerful  antitoxic  bodies  which  are  contained  in  the  circulating 
blood  of  the  animal  treated  and  may  be  obtained  from  the  serum  in  a 
form  suitable  for  administration.  The  antitoxin,  if  administered  suf- 
ticientlv  earlv  in  an  attack  of  diphtheria,  fully  neutralizes  the  poisons 
produced  bv  the  bacillus.  In  order  to  be  successful  the  treatment 
must  be  inaugurated  early — the  earlier  the  better — and  the  agent  must 
be  administered  in  a  suthcient  quantity. 

Diphtheria  antitoxin  may  also  be  used  for  immunizing  individuals 
exposed  to  infection  by  the  bacillus.  The  introduction  of  an  adequate 
amount  of  antitoxin  anticipates  infec- 
tion and  protects  against  the  toxin 
which  would  otherwise  exert  a 
deleterious  action  on  the  tissues  of 
the  bodv  even  before  symptoms  be- 
came manifest. 

Tetanus  is  a  specific  infection  due 
to  the  Bacillus  tetani-  (Xicolaier). 
The  organism  is  3  ,".  to  5  ,".  long.  0.3 


Fig.  b;.— BAdiit 


TKTAM.      PfRE  Cfl.TV«E   r«>l 
WulNll. 


to  0.7  ,"  thick,  motile  (except  |  *_^ 
in  the  spore  stage),  flagellated,  and 
develops  involution  forms;  drum- 
stick ends  are  seen  on  many  of  the 
bacilli  and  are  evidences  of  spore 
formation.  The  spore  is  almost  al- 
ways at  one  end.  Under  ordinary 
conditions  the  bacillus  is  a  strict 
anaerobe,  but  may.  by  prolonged 
cultivation,  be  made  to  grow  in  the 
presence  of  air.  It  liquefies  gelatin 
and  is  feeblv  gas-producing.  Deep 
first  as  a  faint  cloud  from  which  lateral  projections  are  formed,  lique- 
faction proceeds  slowlv,  gas  bubbles  appear,  and  the  organism  gradually 
forms  a  deposit  on  the  bottom  of  the  tube.  It  does  not  lujuefy  solidified 
serum.  In  bouillon,  excluded  from  oxygen,  development  is  ra])id.  the 
medium  becomes  cloudv,  fine  gas  bubbles  appear,  and  eventually  the 
organisms  are  precipitated.     Cultures  give  off  a  famt  odor  resemblnv.- 


stab   cultures  in   gelatin   develoj) 


>  For  the  T)rcparation  of  antitoxin  .sec  chantt-r  on  Bactcnolopc  Technir 
'Scf  rtfcrcncts  in   foot-note  on  n.  81.    Moschocowitz.  "Annals  of  - 
\lbanv  Med.  Annals."  Jan..  IQ04:  Vincent.     . 

p.   450       Holbeck,   "Deut.  med.   Woch        ^ 
Bakt  ."  Oct.    17.    n)04.  p-   y^i       Sachs.      1 

Wien.  klin.  WckH."  jan    r • 

471.     Marinesco.  "C.   R    > 
Tibcrti,  "Ccntralbl.  f.   Bakt         ...->r     ni 
•  Arch,  f    exper     I'ath.    n     I' 

•^.■^    :.n.l  Snrv     I^air  ."  .\liril  7  . 


iQoo.  vol.  xxxii;   Eltinj;. 
rinst.    Pasteur."  July  25.    1904. 
5.    igos-     Creite.    "Ccntralbl.    f. 
klin.  U'och."  1904.  No.  16.     Zupnik 
montmerot.  Th^se  de  Paris.   1904-  N 
mo4.  vol.  57.  p.  62. 
Meyer  and' Ransom. 
Richardson.  "P--'  •- 


122  GEXERAL    PATHOLOGY. 

that  of  burning  horn.  In  botiillon  the  reaction  becomes  clearly  alkaline; 
milk  is  rendered  amphoteric  without  coagulation.  The  organism  does 
not  grow  below  14°  C.,  develops  poorly  at  18°  C,  the  optimum  tempera- 
ture is  37°  C,  although  cultures  may  be  obtained  at  42°  C.  Spores 
resist  six  hours'  exposure  to  80°  C,  but  are  killed  by  steaming  for  one 
hour.  Their  resistance  to  chemic  disinfection  is  also  great.  Miquel 
has  shown  that  in  earth  they  may  live  sixteen  vears. 

DciJioustratioii. — The  organism  may  be  stained  with  any  of  the  basic 
anilin  dyes  and  is  Gram-positive;  the  spore  is  more  resistant  and  often 
stains  at  the  periphery  only.  The  tetanus  bacillus  is  dil!icult  to  obtain 
in  culture;  the  best  results  are  secured  by  making  anaerobic  cultures 
which,  when  fully  developed  and  containing  drumstick  organisms,  are 
exposed  to  a  temperature  of  80°  C.  for  forty-five  minutes;  this  treatment 
usually  destroys  the  associated  bacteria.  Richardson  recommends 
cultivation  in  blood-serum  at  37°  C.  for  several  days,  using  tissue  or  pus 
from  the  wound.  The  growth  of  symbiotic  organisms  consumes  the 
oxygen  and  permits  the  tetanus  bacillus  to  develop.  The  resulting  semi- 
fluid offensive  mass  is  then  subjected  to  heating  and  anaerobic  cultures 
are  made.  The  presence  of  drumstick  bacilli  indicates  that  the  culture 
contains  the  tetanus  or  pseudotetanus  bacillus  described  b\-  Bain.^  The 
latter  organism  is  Gram-negative,  non-pathogenic  for  guinea-pigs;  does 
not  liquefy  gelatin  or  glucose-gelatin,  and  glucose-agar  cultures  are  un- 
like the  true  tetanus  bacillus. 

Pathogenesis.— The  tetanus  bacillus  usually  infects  man  and  horses, 
although  mice,  white  rats,  and  guinea-pigs  are  susceptible.  In  the  tis- 
sues the  growth  of  the  organism  is  usually  restricted  to  the  point  of  in- 
oculation. According  to  Holbeck,  there  are  four  cases  on  record  in  which 
the  bacillus  has  been  found  in  the  blood;  Creite  has  isolated  it  from  the 
lungs.  Manifestations  due  to  the  bacillus  are  brought  about  entirely 
through  the  action  of  its  powerful  toxins,  of  which  Prieger  found  that 
0.000005  g^-  would  kill  a  mouse.  According  to  Kupnik,  tetanus 
toxin  exerts  a  local  action  on  the  muscles  or  the  nerve-endings  in  the 
muscle,  but  all  observers  agree  that  its  chief  manifestation  is  brought 
about  by  its  influence  on  the  motor  cells  of  the  spinal  cord.  Wassermann 
showed  that  tetanus  toxin  became  firmly  attached  to  nerve  tissues;  in 
discussing  the  problems  of  immunity  I  have  already  referred  to  this 
fact.  Recent  studies  by  a  number  of  investigators  indicate  that  the 
poison  reaches  the  nerve-centers  by  passage  along  the  larger  trunks 
rather  than  by  the  general  circulation,  as  previously  believed ;  this  fact 
offers  an  explanation  for  the  occasional  occurrence  of  symptoms  begin- 
ning in  the  muscles  near  the  point  of  infection.  In  addition  to  its  action 
on  the  nervous  elements  it  has  been  shown  that  the  bacillus  produces  a 
hemolytic  poison. 

Postmortem,  areas  of  hyperemia  may  be  found  in  the  spinal  cord: 
under  the  microscope  points  of  hemorrhage  are  sometimes  found  with 
moderate  alteration  in  the  nuclei  (karyolysis)  and  conspicuous  changes 
in  the  Xissl  bodies  (tigrolysis)  of  the  motor  cells.  Marinesco  has  shown 
that  important  alterations  in  the  neurofibrils  are  also  present,  and  Odier 
has  demonstrated  degenerative  changes  in  the  nerves.  The  alterations 
found  in  the  muscles  are  the  result  of  the  spasm  and  not  due  directly  to 
the  action  of  the  tetanus  poison.  They  consist  in  microscopic  or 
^  "Jour,  of  the  Boston  Soc.  of  the  Med.  Sciences,"  1901,  vol.  v,  p.  506. 


BACTKKIA   AS   CAl'SES  OF   DISEASK. 

nuicTosco])!*.-  hcinorrliages  and  occasionally  fragmentation  of  the  muscle 
libers  or  even  v;r<>-s  tears. 

Tetanus  Antitoxin.  -Tetanus  is  probably  the  best  known  example  of 
a  disease  produced  bv  a  toxic  microorganism;  for  tins  reason  much  was 
hoped  for  the  antitoxin  treatment  of  the  affection.  An  effective  anti- 
toxin can  readilv  be  obtained  from  immunized  animals,  and  it  is  easily 
established  that  it  efficiently  neutralizes  the  ]joison  i>roduced  by  the 
bacillus.  Its  administration,  however,  in  cases  of  tetanus,  has  been 
disap])ointing.  This  well-recognized  clinical  result  may  depend  upon  the 
toxin  having  become  firmly  anchored  to  tissues  l)efore  symptoms  mani- 
fest themselves,  the  antitoxin  being  administered  too  late  to  i)revent 
irreparable  damage.  Recognizing  that  the  toxin  acts  intensely  u])on 
the  central  nervous  system,  subdural  injection  of  the  antitoxin  has  1>een 
practised,  but  even  when  administered  in  this  manner,  its  influence  on  the 
disease  falls  far  short  of  our  expectations.  The  best  use  to  which  the 
antitoxin  has  been  put  is  for  the  purpose  of  immunizing  individuals  in 
whom  infected  wounds,  likely  to  give  rise  to  tetanus,  have  been  re- 
ceived. 

Meat  Poisoning. — The  consumption  of  meat  in  wliich  bacterial  decom- 
jtosition  has  led  to  the  production  of  toxic  substances  gives  rise  to  a 
varietv  of  intoxications,  among  which  should  be  mentioneil  botulism, 
due  to  a  toxin  produced  by  the  Bacillus  botulinus.'  The  germ  is  4  ." 
to  6  ."  in  length  and  0.9  ,"  to  1.2  "  in  thickness,  strictly  anaerobic,  fla- 
gellated, slightly  motile,  growing  as  low  as  16°  C.  and  up  to  40°  C.  with 
an  optimum  temperature  between  25°  C.  and  30°  C.  The  spores  are 
killed  bv  exposure  to  80°  C.  for  one  hour.  It  liquefies  gelatin  with  the 
evolution  of  gas,  produces  acids,  among  which  may  be  mentioned  butyric 
acid,  but  does  not  coagulate  milk. 

Dcmoiistraiioti. — The  Bacillus  l)otulinus  stains  by  the  usual  methods, 
and  mav,  with  care  in  differentiation,  be  tinged  by  the  method  of  Gram. 
The  flagella  are  difficult  to  stain.  Cultures  may  readily  be  obtained  by 
the  usual   anaerobic  methods. 

Patliof^otcsis. — The  organism  does  not  grow  readily  in  the  living  tis- 
sues of  man  or  low^er  animals,  but  exerts  its  disease-producing  quality 
bv  means  of  poisons  of  extreme  activity.  Growing  in  pork,  sausage,  or 
other  meat,  the  elaborated  poisons  are  retained  in  the  food  and  manifest 
their  deleterious  action  after  the  food  is  taken.  The  studies  of  Marincsco, 
Kempner  and  Pollack,  and  also  Pollack  and  Brieger,  have  shown  that 
the  toxin  afTects  particularly  the  central  nervous  system,  the  ganglion 
cells  of  which  mav  be  the  seat  of  marked  chromatolysis.  Animals  may 
be  immunizeti  to  the  action  of  the  poison,  and  an  antibotuliu  has  been 
suggested    for    treating   the  intr)xicati<)n  j.rodiucd   bv  the  germ  ]if)ison. 

Anthrax,-    Malignant     Pustule,    Mycosis    intestinalis,    Anthracemia, 

'  See  work.';  referred  to  in  foot-note  on  p.  81.  ,,  ,    /    n   1 

'  See  works  referred  to  in  foot-note.  p.  81.     Scaghosi.  •Cenlralbl.  f.  Bakt 
1004,  Bd.  xxxvii.    Pruszvnski.  "Gaz.  lekarska."  Nov.  la.  1Q04.     Skczclv.  •Zeit    f 
Hvg.."  xliv.  1903.     Topson  and  Ghri.skev,  "Proc.  Path.  Soc.  of  Phila."  Jan..  1000 
Gilruth,  "Lancet,"   Feb.  4.  190^.     Heim.  "Munch,  med.  Woch."  Mairh  S.  u,o\ 
Preisz."Centralbl.  f.  Bakt.."  1904.  Bd.xxxv.  SclK.ttrnuller.'Munch^- 
Sept.  27.  1898.      Le.£:.£;e.  "Milrov  Lectures  on  huhistrial  .Anthrax."     "L 
vol.  i.     Bail   and   Pctterson.   "Centralbl    f    Bakt.,"  vol.   xxxiv-.xx.\    .. 
Vaughan's  article  on   "Cellular  Toxins."     Jour.  Amer.   Med.  .Assoc..     March  3^. 
1903.  p.  S3S. 


124 


GENERAL    PATHOLOGY 


and  Wool-sorter's  Disease  (Splenic  Fever,  Mal-de-nite,  Mihhraiid)  are 
names  applied  to  the  manifestations  of  an  infectious  disease  affecting 
man  and  most  vertebrate  animals  and  due  to  the  Bacillus  anthracis. 
The  organism  is  rod-shaped,  spore-forming,  non-motile,  and  grows  at 
temperatures  between  12°  C.  and  45°  C,  the  optimum  being  37°  C.  The 
spore-free  bacillus  is  killed  at  about  60°  C.  (moist  heat);  the  spores  re- 
quire boiling  for  thirty  minutes.  In  breadth  the  bacilli  measure  from  i  ," 
to  1.5  //;  in  length  the  typical  rod  is  4  ,".  to  8  //.,  but  long  continuous  chains 
often  occur.  In  agar  or  gelatin  plates  the  growth  appears  as  a  small, 
white  dotlet  which  later  develops  hair-like  projections  from  the  periph- 
ery, and  m  gelatin  liquefies  the  medium.  In  bouillon  threads  and 
flocculi  are  formed  which  later  precipitate.  Stab  cultures  in  gelatin 
show  the  characteristic  inverted  fir-tree  growth  consisting  of  a  dense 
stem  along  the  track  of  the  needle  with  innumerable  lateral  projec- 
tions; later  liquefaction  occurs.  The  organism  coagulates  and  pep- 
tonizes milk  with  the  evolution  of 
acid. 

With  regard  to  the  tox'n  produc- 
tion we  are  indifferently  informed. 
Various  substances  have  been  iso- 
lated from  the  cultures  and  from  the 
organism;  some  of  these  are  toxic. 
Vaughan  has  established  the  pres- 
ence of  an  intracellular  toxin,  and 
the  studies  of  Martin  indicate  that 
the  poison  producing  the  local 
symptoms  is  different  from  that 
causing  the  fever  and  other  systemic 
phenomena;  discussions  as  to  the  ex- 
act chemistry  of  the  poisons  elabor- 
ated by  the  bacillus  have  not  been 
illuminating. 

.4  ttenuatioii. — Pasteur  found  that 
by  cultivation  at  43°  C.  the  organ- 
ism became  less  virulent  and  ceased  to  form  spores;  after  twenty-four 
days  it  failed  to  transmit  the  disease  in  susceptible  animals,  which  later 
withstood  inoculation  with  bacilli  grown  at  the  same  temperature 
(42°  C.)  for  twelve  days;  animals  receiving  both  these  vaccinations  be- 
came immune  to  virulent  bacilli,  although  the  insusceptibility  was  of 
relatively  short  duration,  not  exceeding  one  year.  Sobernheim  ^  immun- 
izes by  the  simultaneous  administration  of  5  c.c.  of  anti-anthrax  serum 
and  0.25  to  0.5  c.c.  of  culture.  Anti-sera  have  been  prepared  by  Sclavo, 
Sobernheim,  Mendez  and  others.  Sclavo  obtains  his  serum  from  im- 
munized sheep,  and  uses  it  not  only  for  producing  insusceptibility  but 
for  the  treatment  of  anthrax  in  man ;  the  mortality  from  anthrax  in  the 
whole  of  Italy  is  twenty-four  per  cent.;  of  the  cases  treated  by  Sclavo's 
serum,  six  per  cent.  died. 

Demonstration. — From    a  case  of  suspected  anthrax  cultures  should 

be  made,  a  guinea-pig  or  mouse  inoculated  with  the  suspected  material, 

and    spreads    from    the    blood    and    diseased    tissue   stained    with    the 

usual    dyes    and    by    Gram's   method.      Frequently    the    films    contain 

'  "Deut.  med.  Woch.,"  1Q04,  Nos.  26  and  27. 


68. — Bacillus  anthracis  in   Blood  of 
Rabbit. 


BAlTEklA    AS   CAUSKS   Ol'   DISEASK.  1^5 

ilemonstrahle  nuniliers  of  Ciram-positive  rods  with  s(iuarely-cut  ends. 
Bv  the  time  characteristic  cultures  have  been  ol)taine{l  the  inoculated 
animal  will  probably  have  died  and  the  demonstration  of  the  organism 
m  its  blooci  is  (juite  conclusive.  Blood  cultures  from  a  patient  are  of 
both    diagnostic   and    prognostic   value. 

I\UliOi:,ciicsis. — In  man  several  closely  related  forms  of  anthrax 
occur;  infection  is  usually  brought  about  by  handling  hides,  carcasses, 
hair,  or  wool  derived  from  infected  animals.  It  is  possible  to  recognize 
three  paths  of  infection, — cutaneous,  intestinal,  and  jjulmonary, — and 
possiblv  to  these  should  be  added  an  occasional  instance  of  blood  infection 
in  which  the  point  of  entrance  cannot  be  determined.  It  is  possible  that 
infection  mav  occur  by  the  bites  of  insects,  and  it  is  certain  that  minute, 
often  unsuspected  solution  in  the  continuity  of  the  surface  epithelium 
mav  permit  entrance  of  the  organism.  A  numl)er  of  cases  of  trans- 
placental  infection   are   on   record. 

Cutaneous  anthrax,  in  over  ninety  per  cent,  of  the  cases,  begins  on  the 
arm.  face,  or  neck.  There  is  rarely  more  than  one  primary  lesion, 
although  four  have  been  observed  in  a  single  case.  The  affection  begins 
as  a  red  papule,  rapidly  develops  into  a  vesicle,  which,  as  it  enlarges,  is 
attended  bv  the  formation  of  a  red  brawny  induration  at  the  base  and 
later  a  necrotic  area  appears  in  the  center.  In  severe  forms  the  edema  is 
most  marked,  and  in  some  cases  the  intense  redness  merits  the  term 
erysipelatous  anthrax,  occasionally  applied.  The  edema  may  be  exten- 
sive, the  nearest   lymph-nodes  usually  are  enlarged. 

When  the  bacillus  enters  by  the  alimentary  canal  intestinal  anthrax 
{Mycosis  intcstiualis)  is  produced.  The  ileum  and  caput  coli  are  j>nn- 
cipallv  affected;  the  mucous  membrane  of  these  structures  is  injected, 
and  not  infrequently  is  the  seat  of  minute  ulcers  and  diffuse  submucous 
hemorrhages.     This  form  is  practically  always  fatal. 

In  pulmonary  anthrax,  blood  infection  (authraccniia)  develops 
earlv.  At  autopsy  the  lungs  are  found  edematous,  often  gelatinous; 
subpleural  ecchymoses  and  effusions  into  the  cavities,  particularly  the 
thoracic,  are  usuallv  present.  In  most  cases  more  or  less  bronchitis  and 
some  enlargement  of  the  bronchial  glands  are  present.  The  bacilli  are 
found  in  large  numbers  in  the  bronchial  mucosa,  which  also  shows  areas  of 
hemorrhage;  the  contained  mucus  may  be  loaded  with  bacilli,  which  are^ 
also  demonstrable  in  large  numbers  throughout  the  tissues. 

No  matter  from  what  point  infection  occurs,  when  the  bacillus  en- 
ters the  circulation  widely  distributed  changes  occur  in  the  tissues. 
The  muscles,  including  the  heart,  are  darker  than  normal,  and  frequently 
contain  minute  hemorrhages;  ecchymoses  may  also  be  found  beneath 
the  serous  membranes;  even  the  meninges  and  brain  are  affected.  In 
man  splenic  enlargement  is  less  constant  than  in  lower  animals.  The 
organ  is  usuallv  increased  in  size,  dark  in  color,  and  the  pulp  diffluent. 
The  bacilli  may  readily  be  cultivated  from  all  the  organs  and  are  often 
present  in  enormous  numbers. 

The  bacillus  of  symptomatic  anthrax'  is  a  motile,  flagellated,  an- 
aerobic, spore-forming  organism.  .^  ."  u>  5  ."  long,  and  0.5  .-'  to  o.O  ,-'  thick, 
with  rounded  ends,  occurring  singly  and  in  pairs.  It  liquefies  gelatin; 
developing  small,  irregular  s])heres  which  later  give  off  lateral  spicules; 
the  cultures  yield  an  acrid,  penetrating  odor  and  the  organism  produces 
'  Sec  works  riftTrf<l  t<>  in  foot-note,  page  81. 


~\ 


126  GENERAL    PATHOLOGY. 

gas  and  acid.  It  rapidly  coagulates  milk.  The  optimum  tempera- 
ture is  37°  C.  to  40°  C,  the  minimum  13°  C.  The  organism  is  extremelv 
resistant  to  heat,  requiring  at  least  one  hour's  boiling  in  order  to  assure 
its    destruction. 

Demonstration. — The  bacillus  stains  by  the  usual  anihn  dyes,  and 
if  subjected  to  prolonged  staining  and  brief  differentiation  mav  be 
made  to  take  Gram's  stain.  Pure  cultures  may  be  obtained  in  much  the 
same  manner  as  directed  for  tetanus  (see  page  122). 

Pathogenesis. — The  bacillus  is  the  cause  of  symptomatic  anthrax 
(black-leg  or  quarter  evil),  known  to  the  French  as  "charbon  svmpto- 
matique,"  and  to  the  Germans  as  "Rauschbrand."  Guinea-pigs  are 
very  susceptible;  natural  infection  occurs  in  cattle,  sheep,  and  rarelv  in 
goats.  Cats,  dogs,  pigs,  rabbits,  chickens,  and  ducks  are  immune.  It  is 
not  known  to  infect  man. 

Influenza^  is  an  infectious  disease  due  to  the  Bacillus  influenzae,  - 
an  extremely  thin  organism  0.2  ,v.  to  0.5  !>■  in  length;  it  is  non-motile  and 
aerobic;  the  optimum  temperature  is  36°  C.  to  38°  C,  and  it  ceases  to 
grow  below  28°  C.  and  above  42°  C;  the  thermal  death-point  is  about 
60°  C.  For  cultivation  a  medium  containing  hemoglobin  is  necessary; 
blood-serum  does  not  serve,  although  blood-smeared  agar  or  media  con- 
taining blood  may  be  used.  On  suitable  solid  media 
the  organism  develops  in  the  form  of  numerous, 
^  small,  transparent,  colorless,    homogeneous    droplets 

Ny^A  which  with  age  take  on  a  yellowish  or  brownish  hue. 

y.^^  ^\  but  do  not   become  confluent.     The  vitality   of  the 

*■**  bacillus   is   low   and    re-inoculations  must  be  made 

Fig.  69.— Bacillus  of      every  third  or  fourth'  day. 

.•\xthrax°ContIin-  Demonstration. — The     Bacillus     influenzas     stains 

'iln  affl''^:i^f^y.       ^^y    the    ordinary    anilin    dyes    but    not    by    Gram's 
800  diameters.  mctliod.     Carbol-fuchsin  diluted  with  nine  parts  of 

water  is  especially  recommended.  In  order  to  obtain 
cultures  appropriate  media  are  inoculated  with  nasal  or  bronchial 
mucus  diluted  with  sterile  water;  a  number  of  tubes  should  be  pre- 
pared, as  associated  organisms  frequently  overgrow  the  bacillus. 

Pathogenesis. — The  bacillus  of  influenza  is  found  in  the  bronchial  and 
nasal  mucus,  rarely  in  the  blood  of  infected  individuals;  in  the  mucus 
from  the  respiratory  passages  it  can  readily  be  demonstrated,  and  often 
persists  long  after  cHnical  recovery.  Fifteen  cases  of  influenza  menin- 
gitis are  recorded.  It  has  also  been  found  in  otitis  media,  conjunctivitis, 
pleurisy,  endocarditis,  encephalitis,  cholecystitis,  pyelonephrosis,  and 
arterial  thrombosis.  Inflammation  of  the  mucosa  produced  by  the 
bacillus  is  of  the  catarrhal  form ;    the  abundant  mucus  contains  varying 

'  Recently  clinicians  have  inclined  to  the  view  that  the  condition  ordinarilv 
called  influenza  is  a  syndrome  which  may  be  due  to  infection  b}'  the  streptococcus, 
pneumococcus,  and  unidentified  organisms.  All  are  agreed  that  one  form  is  due 
to  the  influenza  bacillus.     See  discussion,  Soc.  Med.  des  Hop..  March  10,  1905. 

^  Ghon  and  v.  Preyss,  "Centralbl.  f.  Bakt.,"  1904,  Bd.  xxxv,  p.  31,  ''Biol- 
ogy of  the  Bacillus."  Ricciardi  ("Giornale  Internaz.  d.  Scienze  Med.,"  April, 
1904,  "Vitality  of  the  Bacillus."  Didsburv,  "Annals  of  Otolog\-,  Larvngolog\' 
and  Rhinolog>',"  Dec,  1904,  "Influenza  Bacillus  in  Otitis  Media."  Wright,  "Boston 
Med.  and  Surg.  Jour.,"  April  27,  1905,  "Influenza  Bacillus  in  Pvelonephrosis." 
Jundell,  "Jahrb.  f.  Kinderheilk.,"  1904,  Bd.  59.  p.  772,  "  Influenza  Bacillus  in 
Meningitis."  Heyrovsky,  "Wien.  klin.  Woch.,"  June  9,  1904,  p.  644,  "Influ- 
enza Bacillus  in  Cholecystitis;    references  to  its  Presence  in  Other  Conditions." 


HACTKUIA    AS   CAUSICS   OT    1)1  Si;  ASK  .  I  >; 

numbers  ut  phagocytes  in  which  ihe  baciUi  are  often  found.      Intluenza 
pneumonia  is  of  the  catarrhal  type  and  manifested  by  numerous  small 
foci  of  consolidation.     Such  areas,  examined  histologicallv,  consist  of 
distended  alveoli  containing  polym(jr])honuclcar  and  hvaline  cells  and 
a  viscid  fluid  giving  a  mucin  reaction.     The  fact  that  in  some  cases  the 
exudate  is  particularly  rich  in  polymorphonuclear  cells  inrlicates  that 
the  bacillus  possesses  ])yogenic  powers.      It  has  been  found  in  j)ure  cul- 
ture in  abscesses.     The  organism  is  frequently   associated   with  othi-r 
bacteria,   and,  as   is    well   known, 
influenza  is  not  an  infrequent  com- 
plication of  a  number  of  affections.  ^  ^^>. 
The    bacillus    is    sometimes    asso-                   ^  -  ^ 
ciated  with  the  pneumococcus  in              / 

croupous     pneumonia.        The    in-  \ 

fluenza  germ  is  occasionally  present  '/      >  ,         -  \ 

in  inflammations  of   other   serosa^         l^_  |   '^~   "^'/"^m^   "IvHf^' 
than  the    meninges,   but   is  rarelv         ^-<-i''"'  •  -       ''^r--  'SiiX 

alone.  vy  ^•^?p-<-y'i:^-J^     _--'^-- 

Of  the  toxins  produced  by  the  'i         -«.  ^^^^ 

influenza   bacillus   accurate   infor-  \  .v  "^^i.-;^^^^  •/ 

mation  is  needed.     That  the  symp-  A  ''""^^~-  / 

tomatology  depends  largely  upon 
the  influence  of  one  or  more  poisons 
seems  perfectly  clear;  in  no  other 

way  is   it   possible  to  explain   the       ^-,^  -o.-BA.-.L..rs  or  svMrTo».AT.c  a.vthrax-  lu.- 
svmptoms,  especiallv  the  profound  taveex  Mish.f- fibers  or  isoctLAiEn 

depression,  and    such    sequelas    as 
neuritis  and  myelitis,  which  some- 
times follow  the  disease.     It  has  not  been  possible  to  produce  immunity 
in   animals,   and  it  is  well   known  that  in  man  one  attack  affords  no 
protection  and  relapses  are  common. 

The  Bacillus  pneumoniae'  (bacillus  of  Friedlander)  is  a  pleomorphic 

organism  slightlv  less  than   i  ,"  in  width  and  varying  in  length  from  i  ." 

to  4  ."  or  5  .''.     It  is  aerobic,  non -motile  and  in  tissues  and  secretions, 

encapsulated.     The  optimum  temperature  is  37°  C,  the  minimum  14°  C, 

the  maximum  40°  C.  and    the    thermal   death-point  al)Out  56°  C.     In 

gelatin  stab  cultures  a  round  whitish  surface  eleva- 

„  tion  develops,  from  the  center  of  which,  a  long,  nar- 

^^^'V,  row,  pin-like  projection  extends  downward  into  the 

'^■"^  medium    ("nail-growth").       The    gelatin    near    the 

.   .   ;..  -BAaLLus    of      growth     mav    darken,    gas    sometimes    fonns.    but 

Influenza.    X  looo        »  .        -,  /-v  i  « 

diameters.  Hquefactiou  does  not  occur.     On  agar  and  serum  the 

whitish    or    faintly    yellowish -white,    smooth,    often 

glistening  growth  follows  the  course  of  the  needle  stroke.     In  saccharine 

media  it  produces  acid  with  the  liberation  of  gas,  esjiecially  if  chalk  be 

added  to  the  culture.     Grimbert,   Frankland,  and  others  have  shown 

'  Sec  works  referred   to   in   foot-note  on  paee  .Si        I'hilippi,  "  Munch    :r..  1 
Woch.."  1902,  No.  45.  p.  1884.     BauniRarten.  "Wien.  klin.  Woch.,"  Sept 
1>.  066.     Bernstein.  "Amcr.  Jour,  of  the  Med.  Sci.."  DcccmlHT.  1003.     S- 

Centralbl.  f.  Bakt."  xxxvi.  No.  4.     This  organism  Iwlongs  to  a  group  f"i  which 
Frickc  proposed  the  name  Bacillus  mucosus  rapsulatus. 


128  GENERAL    PATHOLOGY. 

that  all  the  members  of  this  group  do  not  give  rise  to  the  same  fermen- 
tative changes. 

DoJioiistratioii. — The  organism  stains  with  the  usual  anilin  dyes  but 
not  by  Gram's  method;  to  the  latter  statement,  however,  there  are 
occasional  exceptions.  For  staining  the  capsule  in  properly  fixed 
spreads  or  in  section  Friedlander  recommends  the  following:  (i)  Stain 
in  the  following  solution  for  twenty-four  hours: 

Saturated  alcoholic  .solution   of  gentian-violet 50  parts. 

Distilled    water, 100 

Acetic  acid ro 

(2)  wash  one  or  two  minutes  in  one  per  cent,  acjueous  solution  of  acetic 
acid;  (3)  dehydrate  in  alcohol;  (4)  clear  in  cedar  oil;  (5)  mount  in 
xylol  balsam. 

Pathogenesis. — Although  mice,  guinea-pigs,  and  rabbits  are  refrac- 
tory to  small  doses,  they  can  be  infected.  The  organism  is  sometimes 
found  in  the  nasal  mucosa  of  normal  individuals.  It  occurs  in  from 
five  to  eight  per  cent,  of  the  cases  of  croupous  pneumonias  and  in  about 
fifteen  per  cent,  of  the  bronchopneumonias.  The  studies  of  Baum- 
garten,  Stuehlern,  and  others  indicate  that  it  may  be  an  independent 
exciter  of  croupous  pneumonia,  although  usually  it  is  associated  with  the 
pneumococcus.  Occasionally  the  bacillus  is  present  in  endocarditis, 
pericarditis,  and  otitis  media;  it  has  been  obtained  from  the  blood  during 
life.  Cionnini  ^  has  collected  24  cases  of  angina  resembling  diphtheria 
but  due  to  the  bacillus  of  Friedlander.  Etienne  has  shown  that  it  is 
present  in  many  infections;  the  organism  has  been  obatined  in  pure 
culture  from  pus.  It  has  been  encountered  in  pyelonephritis,  cystitis, 
and  infections  of  the  tunica  vaginalis  testis,  epididymis,  and  testicle. 
Occasionally  it  produces  a  true  septicemia,  as  in  the  case  reported  bv 
Jenssen.^ 

Pestis/  Plague,  Bubonic  Plague,  Oriental  Plague,  or  Pestilentia  is  a 
specific  infectious  disease,  endemic  in  certain  parts  of  Asia  and  Africa, 
in  which  regions  and  elsewhere  the  affection  sometimes  assumes  epidemic 
proportions.  The  Bacillus  pestis  is  a  short  rod  with  rounded  ends, 
sometimes  designated  a  coccobacillus;  it  measures  0.3  ,"■  to  0.7/'-  in 
width  and  i  /'.  to  4  //  in  length.  In  cultures  chains  of  coccoid  bacilli 
develop  and   the   length  of  detached  organisms  varies  more  than  in  the 

'  "Rif.  Med.,"  June  17,  1903. 

^  "Miinch.  med.  Woch.,"  July  21,  1903,  p.  1250. 

'  See  workj  referred  to  in  foot-note,  p.  81  Flexner.  "Univ.  of  Penna.  Med. 
Bulletin,"  Aug.,  1901.  Goss,  "Arch,  des  Sci.  Biol,  de  Saint  Petersburg,"  1904, 
No.  5,  p.  429.  Zinno.  "Arch,  de  med.  exper.  et  Anat.  Path.."  Jan.,  1904,  p.  i. 
Handi,  "Zeit.  f.  Hyg.  u.  Infectkrank.."  1904,  Bd.  48,  Heft  3.  Bielonovsky,  "Arch, 
des  Sci.  Biol,  de  Saint  Petersburg,"  1904,  vol.  x.  Kolle,  "Zeit.  f.  Hyg.  u.  Infect- 
krank.." Bd.  xlviii,  p.  368.  Thiroux,  "Annales  de  I'lnst.  Pasteur,"  Jan.  25,  1905. 
p.  62.  White,  "Med.  Record,"  Jan.  28,  1905.  Calvert,  "Jour.  Amer.  Med.  Assoc," 
Jan.  16.  1904.  Rosenau,  Bulletin  No.  4  of  the  Hygienic  Laboratory,  1901.  Har- 
ris and  Arnold.  "Phila.  Med.  Jour.,"  April  7,  1900.  Herzog  and  Hare,  "Jour. 
Amer.  Med.  Assoc,"  Dec.  10,  1904,  p.  1781.  Hankin,  "Jour,  of  Hygiene." 
Jan.,  1905,  p.  48.  Zlatogorofif,  "Centralbl.  f.  Bakt.,"  Bd.  xxxvi,  xxxvii,  1904. 
Durck,  "Ziegler's  Beitr.,"  Supplementary  Heft,  1904,  exhaustive  study  of 
pathological  anatom}-  with  full  bibliography.  Herzog.  Bulletin  No.  23,  October. 
1904,  Biological  Laboratories,  Department  of  the  Interior.  Btireau  of  Govern- 
ment Laboratories.  Herzog,  "Amer.  Jour,  of  Med.  Sci.,"  March,  1905,  p.  504, 
"Suctorial  and  Other  Insects  as  Plague-carriers." 


BACTKKIA   AS   CAUSES  OF   DISKASK. 


I  2y 


tissues.  Polar  siainiii^  is  more  niarkt-d  m  l.acilli  contained  in  the 
tissues  tlian  in  those  derived  from  cultures.  In  agar  containing  two 
to  three  per  cent,  .sodium  chlond.  yeast-like  forms  mav  he  present; 
this  reaction  is  of  value  in  identifying  the  orj^'anism.  In  gelatin  the 
bacillus  at  22°  C.  forms  small,  round,  granular,  yellowish,  refractile 
and  .semi-transparent  colonies  without  luiuefactiori.  The  colonies  on 
agar  are  whitish  and  slightly  transparent  with  irregular  borders; 
the  growth  clouds  bouillon  slowly,  and  after  some  days  deposits  a  Hoc- 
culent  sediment.  A  few  drops  of  cocoanut  oil  or  melted  butter  on  the 
surface  of  the  last-named  medium  causes  the  production  of  growths 
extending  downward  as  conical,  long,  shaggy,  thread-like  projections. 
These  "stalactite"  cultures  develop  only  when  the  medium  is  perfectlv 
still,  the  slightest  agitation  detaching  the  pendulous  masses;  stalactite 


Tl 


le  organism   grow 


IlKKt       ll 


r»5T 


formation  is  of  great  diagnostic  value 
uriantly  in  alkaline  media,  but  a 
faintly  acid  nutrient  facilitates  separa- 
tion of  the  Bacillus  pestis  from  the 
])neumococcus.  The  minimum  tem- 
])erature  is  about  20°  C.  or  slightly 
l)elow.  the  optimum  37°  C.  above 
which  point  the  organism  does  not 
grow  well;  Abel's  experiments  show 
that  it  is  killed  by  boiling  one  minute, 
at  90°  C.  in  five  minutes,  at  70°  C.  in 
ten  minutes,  and  often  dies  after  one 
hour's  exposure  to  5  5°  C.  The  bacillus 
is  slightly  motile,  flagellated,  produces 
indol.  and  is  aerobic,  although  feeble 
growths  may  be  obtained  when  air 
is  excluded.  The  toxins  ])roduced  by 
the  Bacillus  pestis  are  largely,  al- 
though not  exclusively,  intracellular. 
Experimental  studies  and  the 
abundance  with  which  the  bacillus 
is  found  in  the  tissues  indicate  that 
the  organism  is  not  highly  toxic,  cer- 
tainly not  in  the  sense  that  diph- 
theria, tetanus,  and  allied  bacteria  are. 

l)c))ioiistnUioii.—ln  cases  of  suspected  plague  an  enlarged  gland, 
through  a  ])reviously  asepticized  Held,  should  be  jiunctured  by  a  hypo- 
dermic needle.  From  the  fluid  obtained  in  this  way  cover-gla.ss  spreads 
and  cultures  should  be  made  and  rats  and  guinea-pigs  inoculated 
Blood  cultures  are  often  of  great  value  and  should  be  obtained  whenever 
po.ssible.  Open  or  discharging  buboes  fre(iuently  contain  so  many 
concurrent  organisms  that  there  may  be  difficulty  in  isolating  the  plague 
bacillus.  In  the  cadaver  inoculations  and  spreads  from  the  blood  and 
viscera,  and  particularly  the  s])leen.  will  yield  data  re<iui.sitc  for  diag- 
nosis. Inoculated  animals  usually  manifest  more  or  less  local  infiltra- 
tion and  necrosis,  the  adjacent  lym])h-nodes  enlarge,  bacteremia  is 
commonlv  rapidlv  developed,  and  death  frequently  occurs  in  from  two 
to  five  davs.  The  bacilli  are  abundantly  [)resent  in  the  blood  and  organs, 
and  from'both  thcv  mav  be  demonstrated  in  films.     The  Bacillus  pestis 


l-'lO.      -1.  —  HK'.HI.V       Mm.NIHUi       I'MRtliiS 
\KrROTIC        l.YMI'HMlUl.        Sll'HVI.\r. 

BAnLi.1. 
Specimen   fixwl  in  solution  i>(  Kiw.  cmlicdctoH  in 
pir.ilTm    :inil    stained    in    r.irlxil  idluirlin    Mtn 
lorty-eiijht    Imurs.    and    i|ilTiTcnii.ilc<)    !•%    ijU 
rrrin-elhrr      iffarrit.)      Z«-iv<     "^"    rvt    'i.  ,. 
and  I'l  inrh  homoKcni-ou-.  nil  ini: 
live.     ij.  PolymiirphonurUMr  leu- 
Lymphoid  cell.-.,     r.   PhaRCM  vie  . 
h.icilii.     d.  DeKeneraline  phaKoiyr  i  i>ni.iinini. 
lutilli.    The  niuleus  of  this  tell  h.is<lis.ipprarr<l. 


130  GEXERAL    PATHOL()GY. 

Stains  with  the  usual  aniUn  dyes  but  not  by  Gram's  method.  Carbol- 
fuchsin  diluted  with  nine  parts  of  water  may  be  used,  but  the  best  re- 
sults are  obtained  with  carbol-thionin  or  carbol-toluidin  blue ;  prolonged 
differentiation  can  not  be  employed. 

Pathogenesis. — In  man  infection  occurs  by  (i)  the  skin,  (2)  inhaled 
bacilli,  or  (3)  through  the  alimentary  canal.  It  is  commonly  stated 
that  plague  may  be  transmitted  from  animal  to  animal  or  from  animal 
to  man,  through  the  intervention  of  insects,  particularly  fleas.  In  a 
number  of  epidemics  data  supporting  this  belief  have  been  obtained. 
Nuttall  has  studied  the  question  experimentally  and  his  observations  do 
not  support  the  theory.  Rats  are  particularly  susceptible  to  plague  and 
are  commonly  infested  with  fleas.  It  has  been  shown  that  viable  plague 
bacilli  ma}'  be  present  in  the  bodies  of  these  insects,  and  that  certainly 
they  may  convey  the  disease  even  though  there  be  some  doubt  as  to  their 
inoculating  the  bacillus  into  man.  Three  forms  of  the  pest  are  usu- 
ally described:  (i)  the  bubonic,  which  may  be  mild  or  malignant,  (2) 
pest  pneumonia,  primary  or  secondary,  and  (3)  the  septicemic  form. 
Cases  of  latent  and  ambulatory  plague  undoubtedly  occur,  and  possi- 
bly constitute  means  by  which  the  disease  is  disseminated.  The  studies 
of  Herzog  and  Hare  clearly  show,  however,  that  such  cases  are  not 
common. 

In  bubonic  plague  anv  of  the  lymph-nodes  may  be  primarily  affected, 
the  particular  ones  involved  being  determined  by  the  point  of  inoculation. 
Among  people  who  habitually  go  bare-footed  the  inguinal  glands  com- 
monlv  flrst  manifest  the  disease.  In  laborers,  with  infection  through  the 
upper  extremities  the  axillary  glands  are  involved ;  in  other  instances  the 
cervical  Ivmph-nodes  show  the  first  manifestations  of  the  disease.  Sys- 
tematic writers  commonly  divide  the  buboes  into  two  groups,  primary 
and  secondary.  The  primary  bubo  developing  immediately  as  the 
result  of  infection,  and  contiguous  to  the  point  through  which  the  bacillus 
entered,  is  called  a  primary  bubo  of  the  first  order  ;  the  lymph-nodes  that 
enlarge  immediately  adjacent  to  this  lesion  and  are  infected  from  it, 
constitute  primary  buboes  of  the  second  order.  Buboes  resulting  from 
systemic  distribution  of  the  bacilli  are  called  secondary  buboes.  The 
rapiditv  with  which  the  primary  buboes  form,  and  the  intensity  of  the 
alterations  taking  place  in  the  lymph-nodes,  vary  from  slight  indolent 
chronic  swellings  to  rapid  enlargements  with  progressive  softening  due 
to  necrosis  of  the  gland  substance  and  accumulated  cells.  In  frank 
cases  periglandular  infection  rapidh'  develops  and  the  enlarged  nodes 
soon  become  embedded  in  edematous,  cell-infiltrated,  or  partly  necrotic 
connective  tissue.  Histologically  the  lymph-nodes  contain  large  num- 
bers of  the  bacilli,  and  in  the  earlier  stages,  before  necrosis  has  destroyed 
the  affected  tissue,  fibrin  and  numerous  leukocytes  are  also  present. 
Usuallv  these  cells  are  mostly  of  the  mononuclear  type,  many  of  them 
large  and  actively  phagocytic,  and  containing  numerous  pest  bacilli. 
Harris  has  shown  that  mast  cells  are  frequently  found.  Polymor- 
phonuclear leukocytes  are  not  abundant,  and  in  the  absence  of 
pyogenic  infection  the  process  is  one  of  necrosis  and  softening  rather 
than  an  acute  suppuration.  The  blood-vessels  of  the  nodes  are  usually 
thrombosed,  the  endothelium  swollen  and  desquamating,  and  the  walls 
often  destroyed. 

Pneumonic    plague    (plague    pneumonia)    may    follow    the    bubonic 


BAiTKKIA   AS  CAUSKS  OF   DISHASK. 


',?' 


type,  or  result  froiii  inhaUitiou  of  the  organism.  Tlie  lesion  produce.l 
is  of  the  lobular  type,  although  a  lobe  or  more  may  be  solidified.  In 
addition  to  the  hepatized  areas  the  organ  is  the  scat  of  numerous  hem- 
orrhages, edema,  mucopurulent  bronchitis,  and  sometimes  a  fibrinous 
exudate  covers  the  overlying  jileura;  the  Ijacilli  arc  abundantlv  present 
m  the  si)utum  during  life  and  in  the  lung,  bronchi,  and  peribronchial 
glands  postmortem. 

The  bubonic  and  pneumonic  forms  of  plague,  i)articularlv  the  latter, 
commonly  terminate  in  the  septicemic  form.  Cases  of  plague  bacillemia 
occasionally  occur  when  no  primary  point  of  infection  can  be  identified, 
and  the  bacteria  may  be  ])resent  in  the  circulation  of  patients  whfi 
afterward  recover. 

When  death  has  resulted  from  the  disease,  early  and  marked  rigor 
mortis  and  postmortem  lividity  are  usually  present!  The  temy)erature 
may  rise  after  death. 

Buboes  which  may  be  suppurat- 
ing are  sometimes  found  and  con- 
junctival infection  may  be  evident. 
The  muscles  are  frequently  dark; 
the  serous  cavities  are  usually  dry 
and  numerous  petechiae  or  ecchy- 
motic  areas  may  fleck  the  sub- 
serosa.  The  blood  is  dark,  often 
without  clots.  The  spleen  is  en- 
larged, soft,  dark  in  color,  and  on 
microscopic  examination  the  sin- 
uses are  dilated,  the  leukocytes 
increased  in  number,  areas  of 
necrosis  are  present,  phagocytes 
often  abundant,  and  the  charac- 
teristic bacilli  invariably  demon- 
strable, usually  in  large  numbers. 
The  kidneys  are  frecjuently  slightly 
enlarged,  soft,  drip  blood  on  sec- 
tion, and  contain  areas  of  hemor- 
rhage. The  epithelium  is  usually 
granular  and  bacilli  can  be  demon- 
strated in  the  vessels  and  tufts.  Herzog  describes  and  figures  the 
presence  of  hyaline  thrombi  in  the  renal  glomeruli.  The  liver  is 
fre(]uently  slightly  enlarged  and  may  contain  areas  of  necrosis. 
Wilms  observed  marked  swelling,  necrosis,  and  hemorrhage  in  the 
solitary  and  agminated  follicles  of  the  intestine,  hemorrhages  in  the 
mucosa,  and  enlarged  mesenteric  glands  often  containing  necrotic  and 
hemorrhagic  foci.  The  brain  and  spinal  cord  are  sometimes  congested 
and  in  rare  instances  fibrinous  meningitis  and  meningoencephalitis  have 
been  observed.  Congestion,  proliferative  processes,  and  necrotic  lesion.^ 
occur  in  the  bone-marrow. 

An  antitoxin  may  be  prepared  by  the  repeated  intravenous  injection 
of  slowlv  increasing  doses  of  pest  bacilli  until  the  animal  acquires  a 
marked  immunity;  the  horse  is  usually  used.  In  beginning  the  process 
of  immunization  it  may  be  well  to  employ  killed  cultures,  followed  later 
by  living  bacilli.  The  value  of  plague  anti-sera 
attested. 


Fig.   75. — Sectiov  of  Kidney  Showing   Malpig- 
HiAN  Body  Costaintno  Pest  Baolu. 

S'.-ction  li.xcd  in  Koa  solution,  embed  led  in  pamffin 
;ind  slainc<l  in  corboltuluidin  blue  and  dificr- 
entiated  by  glyccrin-cther.  ZeiM  "b"  cvc-picfc 
and  1']  inch  homogeneous  oil-immersion  ob- 
jective. 

a.  Capsule  of   Bowman,     h.    EpI' 
capsule,  some  of  which   (f) 
«/,  d.    Capillaries  in  glomenili 
which  (f.  c.  e,  c)  are  many  pcstN.u  lili. 


h'.« 


II  n  1  ti  irm  1 


132 


C.EXHRAL    PATHOLOGY. 


Haffkine's  protective  inoculation  is  undoubtedly  of  very  great  value. 
The  fluid  used  is  prepared  from  cultures  of  the  bacillus  in  bouillon,  the 
surface  pellicle  being  allowed  to  develop  as  often  and  fully  as  possible. 
The  bacilli  are  killed  by  exposure  to  65°  C.  for  one  hour  and  0.5  per  cent, 
carbolic  acid  added.  From  5  c.c.  to  10  c.c.  of  this  fluid,  depending  upon 
its  strength,  is  injected  subcutaneously.  The  maximum  protection 
appears  during  the  week  following  inoculation  and  probably  disappears 
in  a  month  or  so. 

Chancroid,  soft  chancre,  simple  chancre,  or  non-infecting  chancre 
is  an  ulcerative  process  usually  affecting  the  genitals,  propagated  almost 
exclusively  by  venery,  and  due  to  the  Bacillus  ulceris  mollis^  (Ducrey). 
The  bacillus  is  1.5  ,"  in  length,  0.5  ,"  in  thickness,  with  rounded  ends, 
which  usually  stain  more  deeply  than  the  central  part  of  the  rod.  In 
cultures  long,  dot-like  chains  are  produced.  Pure  cultures  have  been 
obtained  by  a  number  of  observers;  the  germ  does  not  grow  on* the 
usual  laboratory  media,  but  can  be  cultivated  on  rabbit's  blood-serum. 

Davis  secured  cultures  on  alkaline 
agar  containing  one-third  rabbit's 
l)lood,  but  regards  freshly  drawn 
human  blood  as  the  best  medium. 
After  twenty-four  hours  at  37°  C. 
delicate  flocculi  appear  in  fluid 
media  or  the  water  of  condensa- 
tion when  blood  agar  is  used. 
By  flowing  the  fluid  over  the  sur- 
face round,  grayish  colonies  ap- 
pear in  forty-eight  hours.  Evi- 
dence of  spore  formation  has  not 
been  observed. 

Dononstration. — The  organ- 
ism stains  readily,  but  is  easily 
decolorized.  Nicolle  recommends 
carbol-toluidin  blue,  and  Unna, 
polvchrome  methylene-blue.  For 
staining  bacilli  from  cultures, 
Davis  advises  the  use  of  carbol- 
fuchsin  followed  by  brief  dift'eren- 
tiation  in  alcohol,  thereby  bringing  out  the  polar  bodies.  The  organism 
is  Gram-negative,  and  c^uite  difficult  to  stain  in  sections. 

Pathogenesis. — Nicolle  was  the  first  to  inoculate  the  monkey  success- 
fully; the  ordinary  laboratory  animals  are  immune.  The  lesion  pro- 
duced in  man  is  rarely  extragenital.  Ullman  has  been  able  to  collect 
64  extragenital  chancroids.  It  develops  as  a  red  point  advancing  to 
a  papule,  and  later  pustule,  which  ruptures,  exposing  a  deep,  crater-like 
ulcer  the  edges  of  which  are  often  undermined  and  the  discharge  abun- 
dant. The  ulcers  sometimes  take  on  phagedenic  action  and  produce 
wide-spread  destruction.  The  lymph-nodes,  anatomically  nearest  the 
lesion,  enlarge  and  may  suppurate  (chancroidal  bubo).  In  some  cases 
there  is  an  intense,  often  polymicrobic,  mixed  infection  with  other  organ- 
isms, usually  of  the  pyogenic  group. 

^  See  works  referred  to  in  foot-note,  p.  Si.  The  most  important  references 
to  this  organisiri  can  be  obtained  from  paper  by  Davis,  "Jour.  Med.  Research," 
June,  1903,  p. 401. 


Bacillus  ov  Soft  Chancre, 


HACTKHIA    AS   CAUSES  (»!•    DISEASE. 


»33 


I'l.i.   75- 


-Thk  Koch-Weeks  lUntLus. 
sell  and  Surel.)     X  gso. 


(H.tn- 


Conjunctivitis  may  be  produced  by  a  lari^c  number  of  r)r^anisms.  in- 
cluding the  streptt)coccus.  ])neumococcus.  bacillus  of  Fricdlander.  the 
pyogenic  staphylococci,  xerosis  bacillus,  etc.  Diphtheria  sometimes 
attacks  the  conjunctiva.  An  acute,  usually  catarrhal  but  sometimes 
])undent  inflammation  of  this  tissue  is  produced  by  a  small,  immobile, 
(iram-negative  organism  resembling 
the  inlhienza  bacillus  in  morjjhology 
and  cultural  channtcrs.  an<l  usually 
called  the  Koch-Weeks  bacillus,  after 
its  discoverers.  It  is  often  >cen  in  the 
interior  of  the  polymor])honuclear 
leukocytes  found  in  the  conjunctival 
discharge.  It  is  frequently  united  in 
pairs  end  to  end  and  sometimes  forms 
short  chains.  The  bacillus  of  Weeks 
stains  readily,  but  not  intensely, 
with  the  ordinary  anilin  dyes.  Cul- 
tures can  not  be  obtained  on  ordinary 
laboratory  media;  the  organism  grows 
slowly  on  serum  agar,  blood  agar,  or 
serum;  the  best  medium  for  its  culti- 
vation is  agar  containing  one-thiril 
ascitic  fluid. 

The  so-called  diplobacillary  con- 
junctivitis is  due  to  the  Bacillus  lacunatus'  (Morax-Axenfeld).  This 
organism  is  2  ."  in  length,  0.7  ,"  to  i  ,"  in  thickness,  arranged  in  pairs 
placed  end  to  end.  and  sometimes  in  short  chains  of  four  to  six  elements. 
It  does  not  grow  below  30°  C.  nor  above  40°  C;  the  optimum  tempera- 
ture is  37°  C,  and  the  thermal  death - 
point  56°  C.  It  is  an  optional  ana- 
erobe, non-motile,  and  does  not  pro- 
duce spores.  In  streak  cultures  on 
the  surface  of  serum  a  moist,  shining 
growth  develops  along  the  line  of 
inoculation.  The  solidified  serum  is 
gradually  liciuefied.  forming  a  furrow, 
which  at  first  extends  in  depth  only, 
but  later  widens.  Smear  cultures 
develop  as  individual  colonies,  which 
])it  the  serum.  After  cultivation 
through  a  series  of  serum  tubes  the 
organism  may,  in  some  instances,  be 
grown  upon  agar,  where  it  then  forms 
"translucent,  discrete  colonies,  like 
dewdrops."  In  bouillon  containing 
one-third  serum  a  turbidity  quickly 
develops,  which  is  not  lessened  by 
the  occurrence  of  a  grayish -white  deposit  on  the  sides  and  bottom 
of  the  tube.     The  organism  requires  frequent  transplantation. 

'  Stf    works  referred    tn  in    foot-note,  page  81.      For  careful  study  of  this 
organism   sec  paper  by  J.  W.  Eyre.  M  S     >i  f 
Bact."  vol.  vi.  .\<».  I.  May.  iSqq. 


Fig.  76. — BAnLi.cs    i.Acts-ATvs. — {H>insfU  uml 

Surrt.)       •   o;o. 


p-itl. 


:>...! 


134 


GENERAL    PATHOLOGY. 


Deuioiistratioii. — The  Bacillus  lacunatus  stains  slowly  but  clearlv 
with  the  usual  anilin  dyes ;  the  best  results  are  obtained  with  an  aqueous 
solution  of  Bleu  dc  Ronx.  The  reaction  to  Gram's  stain  is  peculiar, 
partial  decolorization  taking  place;  the  staining  is  never  characteristic- 
ally that  generally  obtained  by  Gram's  method.  This  peculiaritv  is  to 
be  utilized  in  identifying  the  organism. 

Patliogaiesis. — The  bacillus  is  not  pathogenic  for  animals.  In  man 
it  is  found  in  cases  of  subacute  and  chronic  conjunctivitis  and  may  be 
present  in  large  numbers.  The  disease  has  been  produced  experiment- 
ally by  inoculating  the  human  conjunctiva. 

The  Bacillus  pyocyaneus^  (Gessard,  18S2)  is  a  short  delicate  rod  i  ,". 
to  1.5  ,"  long,  0.5  ,".  wide,  motile,  aerobic,  and  growing  readily  at  tempera- 
tures between  20°  C.  and  37°  C.  Under  various  influences,  particularly 
the  addition  of  an  antiseptic  to  the  medium,  long  chains,  irregular  rods, 
and  even  spirals  may  be  produced;  gelatin  is  liquefied,  and  in  this 
medium  as  well  as  bouillon,  agar,  and  milk  a  greenish  tinge  is  produced; 

on  solid  media  the  surface  presents 
a  peculiar  metallic  luster.  In  addi- 
tion to  the  greenish  pigment  (pyo- 
cyanin)  the  organism  produces 
pyox  an  those,  pyofluorescin,  a 
mucinoid  substance,  and  both  intra- 
cellular and  extracellular  toxins. 

Demonstration. — The  Bacillus 
pyocyaneus  stains  by  the  usual 
anilin  dyes  and  is  Gram-negative. 
By  plate  methods  it  is  easily  iso- 
lated. 

Pathogenesis. — The  organism  is 
frequently  found  in  green  pus  and  in 
intestinal  discharges,  particularly  in 
the  diarrheas  of  infancy.  Numer- 
ous cases  of  pyocyaneus  septicemia 
have  been  reported.  It  has  leen 
found  in  angina,  peritonitis,  pericar- 
ditis, pleurisy,  various  skin  eruptions,  otitis  media,  and  cvstitis. 
Jadkewitsch  has  described  certain  nervous  manifestations  attributed 
to  this  organism.  It  may  produce  catarrhal  conditions  of  the  mucosa 
which  occasionally  go  on  to  ulceration ;  rarely  it  induces  a  hemorrhagic 
enteritis ;  parenchymatous  degeneration  of  the  liver  and  kidney  is  some- 
times present;  the  spleen  enlarges  and  may  contain  areas  of"^  necrosis. 
Among  the  products  of  this  organism  is  a  'definite  hemolytic  substance 
(pyocyanolysin);  one  of  the  remarkable  peculiarities  of  this  body  is 
its  extraordinary  resistance  to  heat;  the  hemolytic  power  is  not  de- 
stroyed by  exposure  to  120°  C.  in  the  autoclave' 

Gaseous  emphysema  and  other  lesions  may  be  produced  in  man  and 

1  See  works  referred  to  in  foot-note,  p.  81.  Maclntyre,  "Jour.  Amer.  Med. 
Assoc,"  April  23,  1904,  p.  1075,  "Intracellular  Toxins."  Earth  and  Michaux, 
"La  Presse  Med.,"  May  30,  1903,  p.  405,  "Pyocyaneus  Cystitis."  Eastman 
and  Keene,  "Annals  of  Surgery,"  Nov.,  1904,  "Pyocyaneus' Septicemia."  Jor- 
dan,_  "Trans.  Chicago  Path.  Soc,"  Dec.  8.  1902,  "On  the  Nature  of  Pvocvan- 
olvsin . " 


I'IG.   77  HAOri.US    PYOCYANEUS. 


HACTKKIA    AS  CAUSHS  OF   DiSliASE.  I3S 

lower  animals  as  the  result  of  infection  by  the  Bacillus  aeropenes 
capsulatus. '  The  organism  measures  3  ,"  to  6  ,"  in  length  an<l  1  -  t<> 
1.5  ,"  in  thickness.  The  bacillus  is  a  strict  anaerobe.  In  cultures  long 
rilaments  and  chains  are  often  formed.  It  usually  proi luces  spores, 
but  sometimes  does  not.  It  is  also  fickle  in  its  lir|uefying  action 
on  gelatin  and  in  the  production  of  capsules;  usually  both  arc 
positive.  (las  formation  is  generally  present  in  cultures,  it  softens  with- 
out frankly  liquefying  gelatin,  and  coagulates  milk  with  the  i)roduction 
of  gas  and  acid.  There  is  a  slight  tendency  to  liquefy  solidified  serum. 
The  bacillus  ferments  lactose,  saccharose,  and  mannite.  It  grfiws  at 
ordinary  room-temperature,  but  best  at  37°  C.  ;s])ore-free  cultures  are  killed 
by  58°  C.  in  ten  minutes;    the  spores  require  ten  minutes'  boiling. 

Dc))ioiistratiou. — For  obtaining  pure  cultures  Welch  recommends 
injecting  0.5  c.c.  to  i  c.c.  of  a  twenty-four-hour  old  milk  culture  —or  sus- 
1  tension  of  a  surface  growth  on  agar— into  the  ear  vein  of  a  rabbit, 
which  in  two  or  three  minutes  is  killed  and  placed  in  the  incul)ator. 
After  seven  or  eight  hours  the  body  will  be  found  distended  with  gas, 
bubbles  of  which  may  be  seen  in  tlie  blood  and  heart  cavities.  The 
bacillus  stains  with  the  usual  anilin  dyes;  in  tissues  it  is  Gram -positive; 
the  stain  reaction  of  spreads  from  cultures  is  not  constant. 

Pathoiicitcsis. — The  virulence  of  different  strains  of  the  organism 
is  not  uniform;  some  cultures  ])Ossess  but  slight  jtathogenic  jjowcr.  The 
guinea-pig  is  the  most  susceptible  of  the  laboratory  animals.  In  man 
the  organism  has  been  found  associated  with  emphysematous  gangrene, 
gaseous  abscesses,  genito-urinary  and  gastro-intestinal  affections,  in- 
flammation of  the  pleurae  and  meninges,  puerperal  and  other  infections 
of  the  uterus,  and,  postmortem,  is  a  frequent  cause  of  cavity  formation 
in  the  viscera  (foam-organs,  emphysema  cadaver osiwi).  It  has  been 
ol)tained  in  pure  culture  from  the  blood  during  life.  Leroy  found  it 
in  a  wound  six  days  before  death  of  the  patient.  In  the  infections 
with  which  it  occurs  it  is  frequently  associated  with  other  jtathogcnic 
bacteria. 

Emphysematous  gangrene,  gaseous  abscess,  and  allied  comluuins  in 
which  gas  is  found  in  the  tissues,  may  be  produced  by  other  organisms 
than  those  just  mentioned.  Jacobelli  described  an  organism,  which  he 
calls  the  Bacillus  septicus  aerobicus,  isolated  from  two  cases  of  gaseous 
gangrene.  It  is  not  gas-producing  in  saccharine  media.  Howard  re- 
ports an  in.stance  of  acute  ribrinoi)urulent  meningitis  with  gas  cysts  in 
the  brain  due  to  the  Bacillus  mucosus  capsulatus.  Regnault-  maintains 
that  there  is  no  special  organism  in  the  lesions  associated  with  gas- 
productions  and  has  collated  numerous  reported  cases  of  gaseous  ab- 
scess and  gangrene,  some  of  which  were  due  to  the  colon  bacillus. 
Bacillus  perfringens,  and  other  organisms.  Legros  has  reached  sinfdar 
conclusions.     The  bacteria  producing  gas  in  the  tissues  may  also  give 

>  Sec  work.s  referred  to  in  foot-note.  p.  81 .     Cole,  "Bulletin  of  the  Johns  Il-r 
kins  Hospital,"    Oct..  1002.     Friinkel.    'Virchow's  Arch.,"  1904.  Bd    177    • 
Werner,    'Arch.  f.  Hvg  ,"  1904.  Bd.  1.  Heft  3.     Leroy.  "Jour.  Amer.  Med.  A 
Oct.  24.  1903.  p.  1009.      Dudffeon  and  Sargent.  "Path.  &)C.  of  London.     N.-v    15. 
1904.     The   organism  was  first  descriljcd  by   Welch  and   Xutlall.     'J'^hns    Hop- 
kins Ho.spital  Bulletin."   1S92.  vol.  3.     In  the  Shattuck  Lecture  ("Bull.    Jolins 
Hopkins  Hosp.."  Sept..  kjoo)  Welch  gives  extended  data  concerning  the   organ- 
ism and  the  lesions  produced  by  it. 

»    'Revue  de  Chir.."  July.  1903.  p.  77. 


136  GEXERAL    PATHOLOGY. 

rise  to  degenerative  and  necrotic  changes  in  the  muscles  associated  with 
serous,  serofibrinous,    or  serocellular  exudates. 

Malignant  edema'  is  an  acute  infiltrating  inflammatory  process 
characterized  b}-  more  or  less  swelling  and  rapid  tissue  necrosis  terminating 
in  gangrene,  and  due  to  an  anaerobic,  spore-bearing,  motile  organism 
called  by  Pasteur  Vibrion  septique,  and  by  Koch  the  Bacillus  oedematis 
maligni.  The  organism  is  0.75  ,".  to  i  //  thick  and  3  n  to  5  ,"  in  length, 
sometimes  forming  filaments  1 5  ,".  to  40  //  long.  The  optimum  tempera- 
ture is  37  °  C. ;  the  organism  may  be  obtained  in  culture  at  15°  C. ;  non- 
spore-bearing  rods  are  killed  at  60°  C;  the  spore  withstands  boiling  five 
to  ten  minutes.  In  the  depth  of  agar  cultures  it  appears  as  small 
c  ouds  which  Gould  has  well  described  as  fuzzy  masses;  gas  is  produced. 
Similar  colonies  are  developed  in  gelatin  with  liquefaction  of  the  medium 
and  evolution  of  gas;  milk  is  coagulated. 

Demonstration. — The  bacillus  of  malignant  edema  stains  with  the 
usual  anilin  dyes  and  is  partly  decolorized  by  Gram's  method;  m  peri- 
toneal exudate  it  is  Gram-positive.  Subcutaneous  inoculation  in  the 
guinea-pig  gives  rise  to  hemorrhagic  edema,  exudation  into  the  serous 
cavities,  moderate  gas  formation  in  the  connective  tissues,  and  death; 
successive  passages  through  these  animals  increases  the  virulence  of 
the  bacillus. 

Pathogenesis. — The  germ  is  pathogenic  for  man,  guinea-pig,  white 
rat,  mouse,  cat,  sheep,  goat,  and  horse.  The  chicken,  pigeon,  and  ass 
are  less  susceptible;  in  dogs  often  no  lesion  is  produced.  Cattle  are 
refractory  to  experimental  inoculation,  but  occasionally  contract  the 
disease.  The  bacillus  is  usually  associated  with  other  organisms, 
although  there  are  a  number  of  cases  in  which  it  has  been  found  alone. 
Pasteur  showed  that  the  filtered  exudate  contains  a  poison  fatal  to 
guinea-pigs,  and  several  experimenters  have  obtained  toxic  substances 
from  cultures.  According  to  Kerry,  the  bacillus  decomposes  albumen 
with  the  production  of  the  usual  putrefactive  substances,  including 
fatty  acids,  leucin,  etc.  Animals  may  be  immunized  against  the  toxin 
and  in  this  way  rendered  insusceptible  to  infection  by  virulent   bacilli. 

The  Bacillus  coli  communis-  is  the  most  common  inhabitant  of  the 
intestine  of  man  and  many  lower  animals.  The  organism  is  1.6,".  to 
3.2  ,"-  in  length,  and  0.4  ,".  to  0.8  ,"-  in  breadth.  Oval,  coccoid,  and  diplo- 
coccoid  forms  have  been  described;  filaments  are  sometimes  formed. 
The  germ  is  motile  and  flagellated,  non-spore-bearing  and  usually  gas- 
producing;  it  is  aerobic,  but  can  grow  without  oxygen.  On  gelatin  plates 
it  forms  small,  flat,  grayish  colonies  with  irregular  outline  and  does  not 

'  See  works  referred  to  in  foot-note  on  p.  81.  A  recent  detailed  report  of  a 
casg  and  references  to  other  cases  in  literature,  see  Gould,  "Annals  of  Surgerv," 
October,  1903. 

^  See  works  referred  to  in  foot-note,  p.  81.  The  literature  bearing  on  this 
subject  is  too  exhaustive  to  be  quoted,  but  may  be  traced  from  the  following 
references:  Savage.  "Jour,  of  Path,  and  Bact.,"  Nov.,  1904,  p.  90.  Moore 
and  Revis.  "Jour,  of  Path,  and  Bact.,"  Nov.,  1904.  Gerard,  "Soc.  de  Biol.,"  March 
4.  1905-.  Vaughan.  "Jour.  Amer.  Med.  Assoc,"  Sept.  3.  1904,  p.  643.  Moore. 
"Medicine,"  March,  1903,  p.  189.  Savage.  "Jour.  Path,  and  Bact.,"  March. 
1904,  p.  347.  Ford,  "Classification  and  Distribution  of  Intestinal  Bacteria 
in  Man,"  Studies  from  the  Royal  Victoria  Hospital,  Montreal,  vol.  i.  No.  5 
(Patholog\'.  II);  an  exhaustive  review  of  the  intestinal  bacteria.  Moorhead, 
"The  Practitioner,"  June,  1905.  discusses  septicemia  due  to  the  organism,  with 
review  of  literature.     Trautner,  "Nord.  Med.  Arkiv.,"  1904,  Afd.  ii.  Heft  2,  No.  7. 


BACTKKIA    AS   lATSKS   OF    DISKASK.  I  ^7 

• 

liquefy  the  medium.  Stab  cultures  in  }:jelatin  give  rise  to  a  faint  grayish 
film  on  the  surface  and  a  gray isli -white  streak  along  the  track  of  the 
needle,  with  the  ev(jlution  of  gas.  On  j)otat(i  the  growth  is  moist,  rela- 
tively ra])id,  and  in  older  cultures  assumes  a  brownish  tinge.  Milk  is  usu- 
ally coagulated,  although  some  cultures  retiuire  weeks  to  induce  the 
change;  acid  is  proiluced.  Some  .strains  of  the  organism  vary  from  the 
foregoing  rather  typical  cultures;  gas  ])roduction  may  be  inconspicuous 
or  absent,  motility  scarcely  ])erccptil)le  and  milk  coagulation  long  de- 
laved.  The  most  prominent  distinguishing  difterences  between  this 
and    closely  allied  j)athogenic  organisms  are  given  in  tai)le  on  page  140, 

Dciiionslralioit. — The  colon  bacillus  is  readily  cultivated  and  may 
be  grown  upon  all  the  laboratory  media.  It  may  be  stained  with  the 
usual  anilin  dyes,  but  requires  prolonged  exposure  to  the  staining  fluifl. 
is  easilv  decolorized,  and  does  not  bear  active  differentiation;  it  is  Gram- 
negative. 

Pathoi^ciicsis. — Lesage  and  Macaigne  called  attention  to  the  fact 
that  the  colon  bacillus  found  in  diarrhea  and  intestinal  inflammations 
is  more  virulent  than  when  ol)tained  from  normal  stools;  Ferranini 
demonstrated  that  the  organism  was  more  toxic  for  emaciated  than  for 
well-nourished  animals.  These  observations,  which  have  been  corrob- 
orated bv  others,  establish  two  facts:  (i)  The  colon  bacillus  varies  in  its 
toxicity  and  pathogenesis,  and  (2)  the  resistance  of  the  individual  to 
colon  infections  is  profoundly  influenced  by  the  state  of  the  body  nu- 
trition. Martin,  Carega.  Vaughan,  and  others  have  shown  that  the 
colon  bacillus  (some  strains  at  least)  is  capable  of  elaborating  a  poison 
the  toxicity  of  which  is  not  constant.  Vaughan's  studies  give  us  con- 
siderable information  as  to  the  character  of  the  intracellular  toxin  pro- 
duced by  the  germ.  In  the  tissues  under  different  conditions  changes 
produced  bv  colon  infection  indicate  that  the  poison  is  not  always 
the  same,  or  at  least  in  different  strengths  it  may  cause  dissimiliar 
changes.  The  possibilities  of  chronic  sul)infection  by  the  colon  bacillus 
have  been  mentioned  on  page  89.  It  is  probable,  as  indicated  by  the 
studies  of  Ford,  that  the  colon  bacillus  frequently  enters  the  tissues,  but 
in  such  small  numbers  that  some  special  condition  must  favor  its 
colonization  and  the  production  of  definite  changes.  The  germ  has  been 
found  in  a  great  manv  jiathologic  processes,  sometimes  alone  and 
often  associated  with  other  bacteria.  This  fact  renders  it  difficult  to 
determine  exactly  what  alterations  are  due  to  the  colon  bacillus  alone 
and  which  are  induced  by  the  bacteria  with  which  it  occurs.  Some 
strains  of  the  bacillus  are  definitely  pyogenic  and  may,  without  the  pres- 
ence of  anv  other  microbe,  give  rise  to  definite  su])purative  }»rocesses. 
It  has  been  isolated  in  pure  culture  from  abscesses,  osteomyelitis,  peri- 
tonitis, pleurisy,  pericarditis,  inflammations  of  the  gcnito-urinary  and 
reproductive  organs,  meningitis,  arthritis,  gall-bladder  and  biliary  pas- 
sages, hepatic  inflammations  both  acute  and  chronic,  otitis  media,  con- 
iunctivitis.  pancreatitis,  mastitis,  and  may  be  the  only  demonstrable 
organism  in  infected  %vounds.  In  many  cases  of  apjjendicitis  it  is  the 
only  microl)e  present,  and  this  disea.se.  in  the  absence  of  the  colon  bacil- 
lus, can  not  be  said  to  he  common.  In  the  complications  antl  sequela?  of 
typhoid  fever  the  colon  bacillus  may  be  found  alone  or  with  the  Bacil- 
lus typhosus.  When  any  local  lesion  affecting,  the  circulation  of  any 
part  of  the  intestine  (constriction,  strangulation,  thrombosis,  embolism) 


13^  GENERAL    PATHOLOGY. 

lessens  the  resistance  of  the  intestinal  wall,  the  colon  bacillus,  alone  or 
wath  other  bacteria,  infiltrates  the  afTected  tissues  and  plays  a  most  im- 
portant part  in  the  necrotic  and  inflammatory  processes  that  follow.  It 
is,  therefore,  a  frequent  organism  in  inflamed  hernial  sacs  and  in  periton- 
itis ;  it  has  been  abundantly  proved  that  the  colon  bacillus  mav  reach  the 
peritoneum  without  any  demonstrable  solution  in  the  continuity  of  the 
mtestinal  wall.  Lesions  in  viscera  adjacent  to  the  intestine  are  not 
infrequently  associated  with  the  presence  of  colon  bacilli  in  such  a  wav 
as  to  indicate  that  the  organism  must  have  reached  the  affected  struc- 
tures by  way  of  the  circulation.  This  view  is  especially  supported  bv  the 
constancy  with  which  the  colon  bacillus  is  found  in  the  suppurative  pel- 
vic lesions  of  the  female,  in  splenic  abscesses  and  infarcts,  and  in  the 
tissues  of  the  spleen  after  its  circulation  has  been  interfered  with  bv 
occlusion  of  the  artery,  or  vein,  or  by  traction  upon,  or  torsion  of,  the 
splenic  pedicle.  The  colon  bacillus  is  often  the  only  organism  present 
in  gallstones,  and  a  number  of  observers  have  demonstrated  that  colon 
infection  of  the  gallbladder  and  biliary  passages  mav  be  followed  bv  the 
formations  of  concretions.  Gerard  has  shown  that  it  decomposes  the 
biliary  salts  and  causes  precipitation  of  cholesterin.  Moorhead  has 
fully  established  that  the  organism  may  produce  a  definite  septicemia, 
including  an  associated  endocarditis.  The  colon  bacillus  has  been 
obtained  in  pure  culture  from  the  blood,  and  is  not  infrequently  the  onlv 
microbe  found  in  the  tissues  postmortem. 

Closely  related  to  the  colon  bacillus  are  the  Bacillus  enteritidis  of 
Gartner,  now  known  to  be  a  member  of  a  group  rather  than  a  distinct 
organism,  a  number  of  bacilli  isolated  from  the  intestine  bv  Booker  and 
by  Sternberg  and  others,  and  the  paracolon  bacillus  of  Gilbert  and  its 
allies.'  The  scope  of  this  book  does  not  permit  a  full  consideration 
of  these  organisms  nor  their  relation  to  various  pathologic  processes  with 
which  they  occur.  At  present  we  are  sadly  in  need  of  some  authorita- 
tive study  that  will  definitely  establish  their  position  among  the  bacteria, 
particularly  their  relation  to  the  colon,  typhoid,  and  dysentery  bacilli, 
and  to  the  various  pathologic  processes  in  which  they  have  been  found. 

The  morbid  anatomy  of  paracolon  infection  will  be  considered  with 
the  lesions  of  typhoid  fever  in  the  chapter  on  Diseases  of  the  Alimentary 
Canal  in  Part  III  of  this  work.  The  cultural  resemblance  of  the  para- 
typhoid bacilli  to  the  colon  organism  is  given  in  the  table  on  p.  140.  All 
members  of  this  group  are  capable  of  inducing  inflammatory  and  ne- 
crotic processes,  and  in  the  blood  give  rise  to  agglutinins  (which  do  not 
appear  to  be  specific);  in  addition,  they  are  toxicogenic. 

Typhoid  fever-   is  an  acute  infectious  disease,  usually  water-borne, 

^  The  literature  bearing  on  these  organisms  will  be  found  in  the  excellent 
studies  of  Gushing,  "Johns  Hopkins  Hospital  Bulletin,"  Juh'  and  August,  1904, 
p.  156,  and  Fox,  "Univ.  of  Penna.  Med.  Bulletin,"  April,  190s. 

^  A  very  full  bibliography  of  the  subject  will  be  found  in  Nothnagel's  "Sys- 
tem of  Medicine,"  American  edition,  volume  on  "Typhoid  and  Typhvis 
Fevers,"  edited  by  Osier,  1902.  Studies  in  Typhoid  Fever,  "Bulletin  of  the 
Johns  Hopkins  Hosp.,"  vols,  iv,  v.  and  viii.  The  following  more  recent  papers  mav 
be  consulted  with  regard  to  the  disease  and  its  organism;  Frankel,  "Mlinch.  med. 
Woch.,"  Jan.  12,  1904,  p.  64.  Roily,  "Munch,  med.  Woch.,"  June  14,  1904. 
Rodet,  Lagriffoul  and  Wahby,  "Arch,  de  med.  exp.  et  d'Anat.  Path.,"  July, 
1904.  Rudiger,  "Trans.  Chicago  Path.  Soc,"  Feb.  8,  1904.  Memmi,  "Rif. 
Med.,"  1904,  No.  32.  Front  and  also  Jordal,  Russell  and  Zeitt,  "Jour,  of  In- 
fectious Diseases,"  Nov.  5,  1904.      Duchacek,  "Centralbl.  f.  Bakt.,"  Oct.  17,  1904, 


BACTERIA   AS   CAUSES  OF   DISEASE. 


'  ><> 


Fig.  78.— BAaLLCs  tyi^oscs. 
Pure  culture  containing  a  few  irregular  forms. 


and  jjenerallv  bclieveil  to  l)e  due  to  the  Bacillus  typhosus.  The  morbid 
anatomv  and  complications  of  tlie  affection  will  lie  discussed  in  Part  111 
of  this  book,  in  the  chapter  on  Diseases  of  the  Alimentary  Canal.  Al- 
though infection  usually  occurs  from  drinking  water  containing  the  spe- 
cific organism. epidemics  have  been  traced  to  infected  milk  andtocressand 
salads  contaminated  by  contact  with  water  containing  the  genn.  ?'"• 
microbe  is  readily  conveyed  l)y  flies 
and  possibly  other  insects,  and  ma\' 
in  this  way  be  transported  from 
])lace  to  place. 

The  Bacillus  typhosus  is  rod- 
shaped.  1.5  ."  to  ,:5.5  ,"  in  length 
and  0.5  ."  thick;  longer  filaments 
are  sometimes  formed.  Although 
grow'ths  are  readily  obtained  at  room 
temperature  and  even  at  15°  C,  the 
germ  develops  best  at  37°  C.  and  is 
killed  by  live  minutes'  exposure  to 
t>o°C.  The  typical  organism  possesses 
flagella.  is  actively  motile,  can  be 
grown  anaerobically,  but  develops 
best  in  an  atmosphere  containing 
oxvgen;  it  grows  readily  on  most  of 
the  laboratory  media,  the  surface 
colonies  resemblirtg  some  strains  of 

the  colon  bacillus;  it  does  not  liquefy  gelatin  nor  produce  gas.  The 
colonies  are  more  transparent  than  typical  colon  growths  and  the 
development  is  somewhat  slower.  Its  growth  on  potato,  long  supposed 
of  great  diagnostic  worth,  has  recently  been  shown  to  be  so  inconstant 
that  it  is  no  longer  given  much  weight  in  identifymg  the  organism. 
Usuallv  on  fresh  potato,  normally  acid  in  reaction,  no  growth  is  visible 
for  several  days,  and  the  rapidity  of  growth  is  never 
comparable  to  that  of  the  typical  colon  germ.  Other 
differentiating  points  of  value  are  given  in  the  table 
on  page  140. 

Demonstration. — The  typhoid  bacillus  stains  with 
the  usual  anilin  dyes  and  is  Gram-negative.  The 
microbe  never  stains  intensely  and  does  not  with- 
stand prolonged  differentiation.  Cultures  are  readily 
obtained  and  i.solation  may  be  accom{)lished  by  the 
usual  platingmethods. 

J'atlioi^ini-sis. — Most  of  the  attemf)ts  to  produce 
tvphoid  fever  in  animals  have  been  entirely  negative.  It  is  not  known 
that,  under  natural  conditions,  any  of  the  lower  animals  are  subject  to  the 

I-.  161,  and  Nov.  8.  1904,  p.  326.     Thavcr,  '•Johns  Hopkins  Hospital  PMllftin." 

Oct.,    1004.     Wright.    'A   Short  Treatise  on    Antitvphoid    Inoculat  »; 

"Practitioner."  March,  1Q04;    "Brit.  Med.  Jour.,"  Nov.  12.  1004      '  '^•. 

"La  Presse  Med."  Dec.   10,   1904.     Natten-Larrier,    'La  V            "  7- 

1004.  p.   770.     Voskressensky,  "Prakt.   Vratch."   Nov.   20  ;i- 

tracted  in  the  laboratory).     Atlossoff.   '"Ar"    '       ■'■    '  '"-  ^ 
1004.   p.    701.   on   experimental   production 
references  to  importan;   T,.-.ip.rs  .  .n  .i-.'vImi  iti.c 
Bacteriologic  Technic 


.  7u.  — 11  A  L  1  I  1.  L  S 
TVPHOSITS,  SHOW- 

I  N  G  Flagella. — 
{Gould.)  X  laoo  di- 
ameters. 


I40 


GENE  R  A  L    P  A  T 1 1  ()  LOG  V . 


TABLE    SHOWING    RESEMBLANTES    AND    DISSIMILARITIES  OF    THE 

BACILLUS  TYPHOSUS,   BACILLUS  COLI.  BACILLUS  DYSENTERUqi, 

AND    PARATYPHOID    BACILLUS. 

(Compiled  bv  Dr.   Rosexberger.) 


B.ACILLUS    TYPHOSrS. 


Molility, Very  active. 

Flagella, i  Upon  sides  and  ends 


13.\cii.i,rs  COLI. 
Active. 


B.\C1LLLS 

dysenteri.k 
(Shig.a). 


Paratyphoid 
Bacillus. 


Jrownian      move-   Active, 
nient . 


Mostly  upon  sides.    Xot  demonstrated    Upon    sides     and 
in  ail  strains.  ends. 


Litmus  milk May   acidulate,   never    coagu-    Acidulates      and    Xo      acidulation,    Slight    acid    reac- 

lates.  coagulates.  no  coagulation.        tion. 


Bouillon Cloudy,  with  or  without  for-  Cloudy,  may  form  Cloudy,  no   pelli-    Cloudy,  may  form 

mation  of  pellicle.  pellicle.                      cle.                              pellicle. 

Potato Generally  a   whitish    inxisihle  Grayish-white    to  Grayish-white    to    Grayish-white. 

growth.  chocolate  brovin.      yellowish-brown. 

Gelatin   shake, Xo  gas,  no  liquefaction. 

Indol, 


None. 


Gas,  no  liquefac-  |  No  gas,  no  lique-    No  gas,  no  lique- 
tion.  ,     faction.  faction. 


Preseat. 


None. 


None. 


-Agglutination     with 

typhoid   serum.  . .    Positive. 


Xo  reaction. 


Usually  no  reac- 
tion except  in 
low  dilutions. 


Fermentation        on 

mannite    media,. .  I  None.  Present. 

Xeutral    red   lactose  -i.              „          .  , 

agar Mav     turn     yellow,     but  no     Turns  yellow  with 

fluorescence'     (reaction  not        fluorescence  (re 

constant).  action  not  con- 
stant). 

Odor 1  Xot  characteristic.  Fecal. 

Pyogenesis '  Produces  a  typical  pus.  Pyogenic. 


Litmus  lactose  agar 

plates, Colonies  blue.  Colonies  pink. 

Hiss's^   water-serum 

mixture, !  Xo  coagulation.  Coagulation. 

Toxin       I  Intracellular    and    extracellu-    Intracellular. 

lar. 


Fresh  .semen. 

Produces  fibrino- 
purulent  proc- 
esses, especially 
i  n  peritoneal 
ca\"itv. 


Colonies  blue. 


Xot  characteristic. 


Colonies  blue. 


No  coagulation.        Xo  constant  reac- 
tion. 

Intracellular    and    Intracellular     and 
extracellular.  extracellular. 


^  Hiss  ("Jotir.  Med.  Research,"  1902,  n.  s.,  vol.  iii)  recommends  for  the  dif- 
ferentiation of  the  colon  and  typhoid  organisms  a  medium  composed  of  horse 
serum  one  part,  and  sterile  distilled  water  two  to  three  parts.  The  mixture  is 
rendered  slightlv  alkaline  to  litmus,  tinted  with  litmus  tincture,  and  heated  in 
an  Arnold  steain  sterilizer,  with  cover  off,  until  mixture  becomes  opalescent. 
The  requisite  percentage  of  anv  sugar  desired  is  now  added  and  the  medium  dis- 
tributed in  tubes  which  are  sterilized  in  an  Arnold  steam  sterilizer  twenty  to 
thirty  minutes  on  three  successive  days.  The  colon  bacillus  turns  the  blue 
litmus  pink,  ferments  the  sugar,  and  coagulates  the  medium:  the  typhoid  bacillus 
docs  not  coagulate  the  medium  nor  ferment  the  sugar.  Dr.  Rosenberger  has 
obtained  the  same  results,  using  flviid  from  pleural  effusion. 


BAITKKIA    AS   CAUSES  OF   DISEASE. 

disease,  a  tact  which  nuhlales  against  successful  experimentation,  (irun 
baum  believes  that  he  has  ])roduce(l  the  disease  in  the  monkey,  and 
Atlossoff  in  rabbits,  inoculation  exjieriments  in  the  lower  animals  may 
give  rise  to  bacteremia,  and  by  passing  the  organism  through  rabbits  or 
guinea-pigs  its  virulence  may  be  materially  exalted.  With  regard  to  the 
toxins  produced  bv  the  germ  we  are  not  fully  informed.  The  studies  of 
Martin.  Sanarelli.  and  \'aughan  indicate  that  the  most  active  jjoison  gen- 
erated bv  the  microbe  is  an  endotoxin.  The  necroses  an<l  endf>thelial  jiro- 
liferation  that  characterize  typhoid  infections  are  clearly  of  toxic-  action: 
the  germ  also  produces  a  hemolysin.  Animals  may  readily  be  immunized 
to  the  tvphoid  bacillus,  and  the  serum  of  patients  recovering  from  the 
disease  possesses  antityphoidal  properties.  In  typhoid  fever  agglu- 
tinins for  the  bacillus  are  found  in  the  blood  and  the  Widal'  test  is  of 
great  value  in  diagnosis. 

Aniiivphoiii  WuTiiialiou. — Chantemesse  and  Widal  in  1888  demon- 
strated the  possibility  of  protecting  mice  against  the  typhoid  l)acillus. 
and  in  uSgg  Chantemesse  vaccinated  his  hospital  internes  by  a  method 
which  has  been  worked  out  with  greater  detail  by  Wright.  The  same 
principle  is  applied  as  in  vaccination  against  cholera,  consisting  of  the 
hypodermic  injection  of  suspended  ty]>hoid  bacilli  killed  by  ex])osure  for 
five  minutes  at  60°  C.  A  local  reaction  follows  the  injection,  and  by 
the  end  of  a  week  or  ten  days  the  blood  of  the  inoculated  individual 
contains  agglutinins  and  its  bacteriolytic  action  toward  the  typhoid 
bacillus  is  materially  increased.  The  dose  of  the  vaccine  depends  upon 
the  virulence  of  the  organism;  Wright  uses  a  killed  bouillon  culture. 
The  immunitv  produced  is  probably  not  great,  nor  of  long  duration. 
Whatever  beneficial  results  may  be  obtained  by  the  inoculation  there 
is  everv  reason  to  believe  that  they  are  increased  by  repeating  the 
injection. 

Dysentery  is  a  form  of  colitis  or  enterocolitis,  the  morbid  anatomy 
of  which  will  be  considered  in  Part  III  of  this  book,  in  the  chapter  on  Dis- 
eases of  the  Alimentarv  Canal.  At  this  point  it  is  necessary  to  state 
that  there  is  a  form  of  the  affection  due  to  the  Amreba  coli  (described  m 
chapter  on  Animal  Parasites)  and  also  an  endemic  or  epidemic  dysenter>-. 
generallv  believed  to  be  of  an  infectious  nature  and  associated  with  the 
presence  of  an  organism— Bacillus  dysenteriae —recognized  by  Chan- 
temesse and  Widal  (1888),  but  brought  t..  it-  present  position  of  promi- 
nence through  the  investigations  of  a  number  of  observers,  especially 
Shiga  in  lapan.  Flexner  in  America,  and  Kruse-  in  (iennany.  There 
are  clearlv  a  number  of  strains  of  this  organism  which  more  or  less  closely 
approach  the  cultural  characters  given  in  the  table  on  page  140.     The 

'  Sc-c-  Agglutination,  chapter  on  Bacteriologic  Tcchnic. 

'The-  liuraturc-  of  this  subject  has  as.sumcd  colos-sal  proportions  llu 
most  imijortant  studies  arc  contained  in.  or  may  be  traced  from,  the  foUowmK: 
Shiga,  Zeit.  i.  Hvg,"  1002.  Bd.  xli,  p.  355.  1-lexner.  'Univ.  of  Pcnna  Med. 
Bulletin.'  Aug.,  n/oi.  Kmse.  -Deut.  mcd.  Woch.."  1901.  No.  23  u.  24:  Broula 
•  Arch  de  med.  Ex].er.  et  Anat.  Path,"  Nov.,  1903.  p-  8".  Eyre  Edinburgh 
Mcd  lour,"  June.  1904.  P  4«q.  a  careful  differential  study  of  the  dysenterv 
bacilli".  Holt,  -Jour.  Amer.  Med.  Asscjc."  Dec.  24.  i«)04.  Hiss  Jour,  of  Mel. 
Research."  Dec.  iyo4.  p.  i-  Eisenberg.  "Wien  klm.  Wc^h.,  Oct.  27.  .004.  ]•■ 
1142.  Stein.  Inaug.  Diss.,  Bonn.  No  46.  loo.;.-  Jurgens.  Ueut.  med.  \\.<-h 
Nov.  12.  icov  Doerr.  'Centralbl.  f.  Bakt.,"  iyo5  Bd^  xxxvni  p.  4J0.  ALs-. 
papers  in  •Suulies  from  the  K<.ckefeller  Institute  for  Medical  Research,  vol. 
li,  1004. 


:42  GEXERAL    PATHOLOGY. 

bacillus  is  flagellate,  usually  motile,  stains  by  the  usual  anilin  dyes,  but 
is  Gram-negative.  It  is  i  ,".  to  3  ,".  long,  0.5  >).  in  diameter,  and  occasion- 
ally forms  short  threads;  it  possesses  no  capsule  and  is  both  aerobic  and 
anaerobic.  The  optimum  temperature  is  37°  C,  but  the  organism  grows 
between  18°  C.  and  42°  C. ;  the  thermal  death-point  is  60°  C.  Im- 
munized animals  and  infected  individuals  produce  antitoxins  and 
agglutinins,  the  latter  active  in  relatively  high  dilutions. 

Pathogenesis. — Intestinal  lesions  may  be  produced  in  some  of  the 
lower  animals  by  the  administration  of  pure  cultures  by  the  mouth  or 
subcutaneously.  Part  of  a  culture  accidentally  swallowed  has  been 
followed  by  dysentery  in  man.  The  organism  evidently  produces  an 
active  poison ;  the  fact  that  killed  cultures  are  much  more  toxic  than  the 
filtrate  derived  from  living  cultures  indicates  that  this  toxic  substance  is 
largely  intracellular  (endotoxin)  or  is  composed  of  two  constituents,  the 
more  active  of  which  is  intracellular. 

The  dysentery  bacillus  has  been  fotmd  in  epidemics  of  the  disease  in 
the  tropic,  subtropic,  and  temperate  climates,  and  in  institutional  dysen- 
teries, such  as  are  occasionally  encountered  in  asylums  and  prisons. 
Numerous  observers  have  isolated  the  organism  from  the  intestinal  con- 
tents of  cases  of  enterocolitis  in  children,  and  an  organism  indis- 
tinguishable from  the  virulent  form  has  been  found  in  the  feces  of  healthv 
children. 

Gay  and  others  have  investigated  the  action  of  antitoxic  sera  which 
have  been  used  in  the  treatment  of  dysentery.  In  some  epidemics 
the  serum  treatment  seems  to  have  been  of  some  value,  although 
beneficial  results  have  not  invariably  been  observed.  Anti-dvsenterv 
inoculations  based  on  the  same  principles  as  anticholera  vaccination 
have  been  tried. 

Cholera^  is  a  specific,  infectious,  communicable  disease,  practicallv 
always  water-borne,  and  due  to  the  Spirillum  cholerae  asiaticae  (Koch). 
The  spirillum  of  Asiatic  cholera  consists  of  short  comma-like  elements 
1.5,".  to  2.5 //  in  length  and  0.5 //.  to  o. 7 ,".  in  thickness.  In  cultures  U-  and  S- 
shaped  forms  and  long  spiral  filaments  occur.  The  organism  is  motile  and 
flagellated  (single  flagellum,  usually  at  one  end  only).  It  may  be  grown 
between  14°  C.  and  42° C. ;  the  optimum  temperature  is  37°  C,  and  thermal 
death-point  55°  C.  Spore  formation  does  not  occur.  In  old  cultures 
involution  forms,  resembling  yeast  cells,  some  of  which  are  suggestive  of 
spores,  are  frequently  present.  The  gro\^^h  on  gelatin  is  most  character- 
istic. In  gelatin  plates  the  surface  at  first  presents  an  appearance  resem- 
bling that  produced  by  sprinkling  the  medium  with  delicate  glass  splinters; 
this  appearance  is  lost  with  beginning  liquefaction.  The  gelatin  plate 
should  be  kept  at  22°  C;  in  about  twenty-four  hours  liquefaction  be- 
comes evident,  and  usually  progresses  so  that  in  a  few  days  the  entire 
plate  is  liquefied.  Under  the  microscope  the  beginning  colonies  are 
granular  with  irregular  borders,  and  white  or  vello wish-white  in  color. 
In  stab  cultures  the  growth  begins  at  the  surface  and  proceeds  along 
the   line   of   puncture.     Liquefaction    commences    at   the    surface    and 

'  See  works  referred  to  in  foot-note,  p.  81.      Bibliography  to  the  older  liter- 
ature will  be  found  in  Allbutt's"  "System  of  Medicine,"  vol.  i.     For  methods  of 
differentiating  the  organism,   see   Kraus,    "Wien.   klin.   Woch.,"   Dec.    10,    1903, 
p.  1382.     Tsuzuki  and  Myisaki,  "Arch.  f.  Schiffs-und.  Tropen  Hyg.,"  July,  1903 
and  Hirschbruch  and  Schiver,  "Centralbl.  f.  Bakt.,"  Sept.  12,  1903,  p.  585. 


H.VCTKKIA    AS   lAlSKS   «)K    DIS  K  ASK. 


caccoinpanios  ihc  i^rowih  aloii*,'  tlu.-  rourso  ot  the;  needle-track.  The  an-.i 
of  litiuelaclion  is  lunnol-sliapcd  and  a  l)u])l»le-likc  expansion  develoj<s 
at  a  point  correspondinj;  to  the  junction  of  the  tajjerin^  funnel  stem  and 
bodv.  Milk  is  not  coaj^ulated.  On  aj^'ar  and  serum  a  thin  whitish 
laver.  later  becoming  brown,  is  jirotluccd;  solidified  serum  is  li(|uehed. 
Ai)undant  growths  can  be  obtained  in  Dunham's  solution  (j  per  cent, 
jieptone  in  water);  cultures  in  this  medium,  twenty-four  hours  old. 
vield  the  indol  reaction  without  the  addition  of  nitrite.  This  is  due 
to  the  spirillum  reducing  traces  of  nitrates  present,  rendering  it  neces- 
sarv  to  add  the  sulphuric  acid  ( i  to  2  drops)  only.  The  reaction  is 
sometimes  called  the  nitro-indol  or  cholera-red  reaction,  and  it  is 
especially  conclusive  if  it  can  be  obtained  by  pure  hydrochloric  acid 
or  oxalic  acid. 

A  number  of  poisons  have  been  isolated  from  the  cultures  and  bodies 
of  the  germs,  but  the  exact  nature  of  these  substances  remains  undeter- 
mined. Extracellular  toxins  have  been  separated  from  filtered  cultures. 
The  experiments  of  Metchnikoflf  and 
Pfeiffer  indicate  that  the  intracellular 
and  extracellular  poisons  are  not  iden- 
tical. Animals  may  readily  be  immu- 
nized against  the  organism,  beginning 
with  killed  cultures  followed  by  in- 
creasing doses  of  living  spirilla.  Such 
sera  possess  slight  protective  and  ther- 
apeutic properties  and  may  be  used  for 
agglutination  or  bacteriolytic  studies 
necessary  in  identifying  the  organism. 
If  the  cholera  spirillum  be  mixed  with 
anticholera  serum  and  injected  into 
the  ])eritoneum  of  a  guinea-pig,  bac- 
teriolysis promptly  occurs;  the  same 
result  follows  the  injection  of  the 
organism  into  the  peritoneum  of  an 
immunized  animal.  Af^i^littiiiiiis  occur 
in  the  blood  of  immunized  animals 
and  in  cholera  patients. 

Dcinoiistratioii. — The  spirillum  of  cholera  stains  by  the  usual  anilin 
dves  and  is  Gram -negative.  Carbol-fuchsin  diluted  with  nine  ]iarts  of 
water  and  used  slightly  warm  is  especially  recommended.  In  sus- 
pected cases  the  organisms  are  ])resent  in  .such  large  numbers  that 
<luring  a  cholera  epidemic,  the  clinical  diagnosis  may  be  corroborated  by 
microscopic  examination  of  films  prepared  from  typical  stools.  The 
Spirillum  tyrogenum  has  different  cultural  characteristics.  The  spi- 
rillum of  Finkler  and  Prior  (cholera  nostras)  grows  more  rapidly,  the 
colonie-;  attaining  a  diameter  of  2  or  3  cm.  in  forty-eight  to  fifty-two 
hours.  The  organism  is  less  virulent  than  the  cholera  spirillum  and 
is  not  agglutinated  by  the  serum  of  cholera  patients  or  cholera-immune 
animals.  The  cholera  nostras  spirillum  gives  the  indol  reaction  much 
later:  cultures  are  fetid  and  the  stools  from  cases  of  cholera  nostras 
much  more  offensive  than  those  of  true  cholera. 

Pathogcucsis. — The  influence  of  the  cholera  spirillum  on  animals 
has  been  referred  to  in  the  preceding  paragraph.-  Animals  under  natural 
conditions    appear   immune    against   cholera   and   the   typical   disease 


Via.    80. — Spirillum    cholera 
Culture. 


144  GEXERAL    PATHOLOGY. 

cannot  he  produced  in  them.  By  neutrahzing  the  gastric  juice  and 
administering  opium  it  has  heen  possible  to  produce  choleraic  symptoms 
when  virulent  spirilla  are  given  by  the  mouth.  Similar  results  have 
occasionally  followed  intraduodenal  injection  of  the  organism.  Labora- 
tory workers  have  been  infected  by  cultures. 

Protective  Inoculation. — Haffkine  devised  a  method  for  securing 
a  certain  degree  of  immunity  to  cholera.  Suspensions  of  cholera  organ- 
isms, possessing  low  .  virulence,  are  injected  subcutaneouslv,  followed 
in  four  to  six  days  by  similar  injections  of  highly  virulent  spirilla.  The 
([uantity  of  the  injection,  in  each  case,  must  depend  upon  the  virulence 
of  the  organism,  and  can  be  determined  by  experiment  only.  This 
method  of  vaccination  has  been  extensively  used,  particularly  in  India, 
and  has  been  generally  approved. 

The  cadaver,  in  cholera,  often  shows  characteristic  lesions.  Rigor 
mortis  comes  on  early  and  is  often  accompanied  by  postmortem  con- 
tractions of  the  muscles.  This  skin,  particularly  of  the  palms  of  the 
hands,  may  be  wrinkled  and  the  features  drawn.  The  tissues  of  the 
body  appear  abnormally  dry,  a  result  brought  about  by  the  abundant 
alvine  discharges.  Petechiae  and  ecchvmotic  spots  are  sometimes 
present  in  the  subserous  tissues.  The  lungs,  spleen,  and  liver  show 
no  constant  change.  The  kidneys  are  swollen,  congested,  and  may 
contain  ecchymotic  spots;  the  capsule  is  less  firmlv  attached  than  nor- 
mal and  the  renal  epithelium  shows  more  or  less  granular,  fattv.  and 
desquamative  change.  The  most  constant  alterations  are  found  in  the 
intestine,  the  lesions  becoming  more  intense  from  the  jejunum  to  the 
ileocecal  valve.  The  mucosa  is  swollen  and  frequently  shows  large 
denuded  areas  or  smaller  spots  of  desquamation;  the  solitary  glands 
are  often  conspicuous  and  the  patches  of  Peyer  hyperemic  and  more 
or  less  tumefied.  Sometimes  the  surface  of  the  membrane  is  covered 
bv  a  grayish  diphtheroid  film.  The  grayish,  rice-water  intestinal  con- 
tents is  loaded  with  desquamated  epithelium,  leukocytes,  and  varying 
numbers  of  red  blood-cells.  The  cholera  spirilla  are  particularly  abun- 
dant. The  lesions  in  the  colon  are  of  a  similar  kind,  but  less  marked 
than  those  occurring  in  the  ileum. 

Tuberculosis. — The  Bacilli   of   tuberculosis^   are  rather  pleomorphic 

'  The  literature  on  the  tubercle  bacillus  is  widely  distributed,  and  the  scope 
of  this  book  does  not  permit  full  references.  Should  the  Report  of  the  Pennsyl- 
vania State  Commission  on  Tuberculosis  be  printed,  the  paragraph  on  tubercle 
bacilli  will  contain  references  to  nearly  three  hundred  articles.  Many  of  the 
older  references  will  lie  found  in  the  works  referred  to  in  foot-note  on  p.  Si .  Among 
the  more  recent  publications  that  may  be  consulted  are  the  following:  "Ttiberculosis 
and  Acute  General  Miliary  Tuberculosis,"  Nothnagel's  "Encyclopedia  of  Prac- 
tice of  Medicine."  American  edition,  1904.  Kober.  "Amer.  Jour,  of  Med.  Sci.," 
Oct.,  1903,  p.  6S4.  "Transmission  of  Bovine  Tuberculosis  to  Man."  Hayward, 
"N.  Y.  Med.  Jour.,"  Oct.  i.  1904,  p.  643,  "Transinission  of  Tuberculosis  by 
Insects."  On  the  morphology-  of  the  organism  consult  Abbott  and  Gilder- 
sleeve,  "Univ.  of  Penna.  Med.  Bull.,"  June,  1902.  Most  of  the  important  litera- 
ture bearing  on  the  metabolic  products  of  the  bacillus  is  referred  to  by  Bulloch 
and  McLeod,  "Jour,  of  Hygiene,"  vol.  iv,  No.  i,  p.  i.  On  the  tuberculins  and 
their  preparations  consult  Koch,  "Deut.  med.  Woch.,"  1897,  No.  14,  p.  209; 
Trudeau,  Baldwin  and  Kinghom.  "Jour,  of  Med.  Research,"  Aug.,  1904,  p.  169. 
"Tuberculin  in  Diagnosis,"  Tinker,  "Johns  Hopkins  Hosp.  Reports."  1903, 
vol.  xi,  p.  535.  On  thermal  death-point  see  Theobald  Smith,  "Jour,  of  Exper. 
Med.,"  1899,  vol.  iv,  p.  233;  also  RuUmann,  "Berl.  klin.  Woch.,"  March  21, 
1904.  On  pathogenesis  see  Trudeau,  "Trans.  Assoc,  of  Amer.  Phys.,"  1903, 
vol.  xviii,  p.  97;  Ravenel,  "Jour,  of  Med.  Research,"  Dec,  1903,  p.  461;  Theo- 
bald Smith.  "Trans.  Assoc,  of  Amer.  Phys.,"  1903,  vol.  xviii.  p.  ioq- 


HACTKkIA  AS  CAUSES  OP  DISEASK. 


organisms  ami  it  scorns  fairly  established  lliat  they  are  closely  relateil 
to  the  actinoniyces;  they  are  ro(l-sha]»e<l  under  certain  ronditinns  onlv, 
and  might  well  be  classed  with  the  stre])t(jthrix  grouj).  It  is  possihle 
to  recognize  three  important  <livisions  of  the  tubercle  bacillus:  (i) 
The  tubercle  bacillus  of  mammals.  (2)  The  tubercle  bacillus  of  birds. 
(3)  The  tubercle  bacillus  of  jjoikilothcmiic  animals. 

The  tubercle  bacilli  of  mammals  show  certain  morphologic  and 
cultural  differences  de|)ending  upon  the  particular  animals  from  which 
each  organism  is  obtained.  For  this  differentiation  we  are  largely  in- 
debted to  Theobald  Smith.  The  following  condensed  description  pre- 
sents the  important  characters  of  the  tubercle  bacillus  found  in  warm- 
blooded animals  and  particularly  that  pathogenic  in  man.  It  is  an 
aerobic,  non-motile,  straight  or  slightly  curved  rod  with  rounded  ends. 
1-5  /'  to  3.5  ."  long  and  0.25  ,".  to  0.5  ,'«  thick;  its  optimum  temj)erature 
is  37.5°  C.  the  minimum  30°  C.  and  the  maximum  rarely  exceeds  40°  C. 
although  it  can  be  made  to  grow  at  45°  C.  The  thermal  death-point  is 
about  68°  C,  although,  under  favorable  conditions  (for  example,  in 
sputum),  the  organism  may  resist  100° 
C.  for  fifteen  minutes.  The  bacillus 
develops  slowly  upon  suitable  media, 
requiring  from  two  to  three  weeks  to 
make  its  appearance  upon  blood-serum 
— a  medium  especially  adapted  to  its 
cultivation.  It  also  grows  upon  glycerin 
agar  and  may  be  made  to  acquire  the 
ability  to  grow  upon  glycerin-free  media, 
although  such  growth  is  attained  only 
after  considerable  'difficulty.  On  the 
surface  of  solidified  serum  it  appears  as 
a  cream-colored  or  whitish  layer,  usually 
dull,  granular,  and  somewhat  wrinkled; 
granularity  and  wrinkling  become  more 
marked  as  the  culture  ages,  and  finally 
the  surface  takes  on  a  bread-crumb 
appearance.  On  glycerin-bouillon  care- 
fully floated  fragments  gradually  extend,  coating  the  Muiaic  with 
a  finely  granular,  white  or  cream-colored  layer  with  a  dull  surface 
eventually  covering  the  medium  and  extending  i  mm.  or  2  mm. 
upward  on  the  side  of  the  flask  or  tube.  In  older  cultures  the  surface 
wrinkles,  the  pellicle  saturates  and  sinks,  after  which  some  slight 
surface  growth  mav  redevelop;  ordinarily,  however,  the  second  film 
is  scanty  and  incomplete.  The  organism  grows  upon  glycerin-agar. 
the  cultures  resembling  those  on  serum.  Ciibnr.'  on  vegetable  mc.Ii.i 
have  been  obtained. 

Pcnionstration. — The  tubercle  bacillus  resiM>  i..^  penetrating  «>  i.-  .. 
of  dves.  but  once  it  has  absorbed  the  stain  is  decolorized  with  difficulty ; 
both  these  qualities  are  dependent  upon  the  fat -like  substance  contained 
within  the  bacillary  i>rotoplasm.  It  can  be  stained  with  most  of  the 
basic  anilin  dyes  and  by  Gram's  method.  It  is  more  readily  demon- 
strated in  films  than  in  sections;  and  in  tissues  supposed  to  contain  the 
bacillus,  better  results  are  obtained  from  the  expressed  juices  than  in 
sections.     Urine  ♦"  bf>  (■v.imiT-ic.l  tdr  mbcrc  1c  bac  illi  should  be  subjected 


Krancho<l  and  !>• 
ous  culu 


146  GENERAL    PATHOLOGY. 

to  prolonged  sedimentation  b}'  methods  given  in  the  chapter  on  Technic 
of  Microscopic  Examination  of  the  Urine.  Sputum  may  be  taken  as  a 
type,  and  the  method  recommended  for  demonstrating  the  bacillus  in 
expectoration  can  be  applied  to  other  pathologic  fluids  and  exudates 
In  the  sputum  search  is  made  for  yellowish,  opaque,  cheesy  particles 
the  finding  of  which  is  facilitated  by  spreading  the  liquid  on  glass  or  in 
the  bottom  of  a  large  Petri  dish.  Selected  material  is  spread  in  a  thin, 
even  layer  on  the  surface  of  the  slide  or  cover-glass,  preferably  the  latter, 
and  is  allowed  to  dry  in  the  air.  The  cover  is  then  fixed  by  passing  it 
through  the  liame  three  times,  following  the  directions  given  in  the 
chapter  on  Bacteriologic  Technic.  Flood  the  film  with  carbol-fuchsin  and 
heat  for  three  to  five  minutes,  not  allowing  the  stain  to  boil  or  become  dry. 
Pour  off  the  excess  of  stain,  wash  in  water,  and  apply  a  few  drops  of 
Gabbet's  acid  methylene-blue,  which  should  be  evenly  flooded  over  the 
film  and  allowed  to  act  two  or  three  minutes.  Wash  the  film  in  water, 
and  if  all  the  red  has  not  been  discharged,  reapply  the  Gabbet's  solution; 
after  the  final  washing  in  water,  dry  and  mount  in  balsam.  In  success- 
ful preparations  the  tubercle  bacilli  appear  as  short  red  rods,  while  other 
bacteria,    the   ground-substance    and   nuclei   of   cellular   elements,    are 

stained  blue.  When  time  is  no 
object,  films  or  sections  may  be 
allowed  to  soak  in  the  stain 
twelve  to  twenty-four  hours  at 
room -temperature,  and  it  is 
probable  that  this  method 
yields  more  satisfactory  results 
than  the  more  rapid  one.  The 
formula  for  carbol-fuchsin  is 
given  on  page  49 ;  Gabbet's  acid 
methylene-blue  counterstain  is 
-*'-.>.=i..'^,r^Vi^  ^^-'"-^--V  prepared   by    adding   2    gm.    of 

Fig.  8?.— Bacillus  tuberculosis.— (Fo« /a^^c/i )  metliylene-blue    tO    lOO   C.C.  of    a 

X  Soo  diameters.  ^  .        r 

twenty-five  per  cent,  aqueous 
solution  of  sulphuric  acid. 
I  am  convinced  that  Pappenheim's^  method  of  decolorizing  is 
superior  to  that  of  Gabbet.  After  staining  with  carbol-fuchsin  and 
without  washing  in  water  the  film  is  flooded  with  a  decolorizing  solution 
prepared  by  dissolving  i  gm.  of  coralin-  in  100  c.c.  of  absolute  alcohol 
and  saturating  this  solution  with  methylene-blue,  after  which  add  20 
gm.  of  glycerin.  The  decolorizing  solution  is  poured  off  and  fresh 
applied,  this  step  being  repeated  four  or  five  times ;  finally  wash  in  water, 
the  excess  of  which  is  removed  with  a  blotter,  dry  the  film,  and  mount 
in  balsam.  Pappenheim  claims  that  by  this  method  smegma  bacilli  do 
not  retain  the  red  dye  but  are  stained  blue.  Sections  may  be  stained 
with  carbol-fuchsin  and  differentiated  by  Gabbet's  method,  or  decolor- 
ization  may  be  accomplished  by  using  a  twenty-five  per  cent,  aqueous 
solution  of  nitric  or  sulphuric  acid  followed  by  sixty  per  cent,  alcohol  and 
water;  after  the  acid  has  been  fully  removed  by  the  alcohol  and  water 
the  tissue  cells  can  be  stained  in  one  per  cent,  methylene-blue  for  five 

1  "Berl.  klin.  Woch.,"  1898.  p.  809. 

^  This  substance  is  also  called  rosolic  acid,  and   I   believe  is  identical  with 
aurin.  t   i 


BACTKRIA   AS  CAUSES  OK   DISKASK.  ,   ,- 

minutes,  followed  by  water,  dehydration  with  alcohol,  and  clearing 
in  xylol,  cedar  oil,  or  oil  of  cloves.  The  clove  oil  tends  to  carry  differen- 
tiation too  far,  and  the  specimens  do  not  keep  well  unless  it  has  been 
thoroughly  removed  by  xylol  or  cedar  oil  before  mounting  in  balsam. 
As  the  l)acilli  may  be  scanty  in  urine  and  pathologic  exuilatcs,  .seilimenta- 
tion  is  important  and  a  number  of  spreads  should  ])e  examined.  As  there 
are  numerous  acid-fast'  bacilli  resembling  more  or  less  clo.sely  the 
tubercle  bacillus,  when  results  by  staining  methods  are  not  satisfactory 
animals  should  be  inoculated. 

.l.i:i,'/////;/.7//o;;. — The  blood  of  tuberculous  patients  contains  agglu- 
tinins for  the  bacillus,  but  the  difficulty  in  securing  and  maintaining 
homogeneous  cultures  free  from  clumps,  and  the  fact  that  our  present 
knowledge  of  the  reaction  indicates  that  it  is  less  constant  and  trust- 
worthv  than  typhoid,  have  prevented  its  general  adoption.- 

Tuberculin  consists  of  certain  extracellular  toxins  of  the  tubercle 
bacillus  and  such  endotoxins  as  are  extracted  by  boiling  glycerin- 
bouillon  cultures  of  the  organism.  For  its  preparation  luxuriant  growths 
of  the  bacillus  on  glycerin  l)Ouillon,  having  attained  their  maximum 
development,  are  boiled,  filtered  through  paper,  and  the  filtrate  con- 
centrated to  one-tenth  the  original  volume;  finally  the  fluid  is  filtered 
through  porcelain.  Tuberculin  has  been  used  for  therapeutic  purposes 
and  for  diagnosis,  especially  for  the  recognition  of  latent  tul^erculosis  in 
bovines.  Cattle  are  tested  by  the  subcutaneous  injection  of  0.3  c.c.  to 
0.5  c.c.  diluted  in  10  c.c.  of  a  0.5  per  cent,  aqueous  solution  of  carbolic 
acid.  In  man  the  dose  should  rarely  exceed  0.5  c.c.  In  tuberculous 
animals,  including  man,  injections  of  tuberculin  are  followed  bv  a  rise  of 
temperature  amounting  to  1.5°  C.  to  3°  C. 

The  cases  of  reported  infection  of  man  by  the  bacillus  of  avian  tuber- 
culosis ^  are  not  convincing;  it  is  certain  that  the  organism  plays  no 
important  part  in  human  pathology-.  The  same  is  true  of  tubercle 
bacilli  obtained  from  poikilothermic  animals.*  Members  of  both  these 
groups  have  been  used  for  immunizing  lower  animals  and  a  few  studies 
have  been  made  on  man;  the  results  so  far  are  not  such  as  to  arouse 
enthusiasm,  although  Trudeau  and  others  have  shown  that  1)V  the  use  of 
bacillary  products  and  the  organisms  themselves  it  is  possilde  to  influ- 
ence the  evolution  of  lesions  resulting  from  more  virulent  organisms. 

Pathogoicsis. — Much  discussion  has  arisen  as  to  the  identitv  of  the 
tubercle  bacilli  ol)tained  from  warm-ldooded  animals.  The  controversy 
has  been  particularly  heated  with  regard  to  bovine  and  human  bacilli, 
and,  while  much  may  be  said  on  both  sides,  I  believe  it  is  safe  to  conclude 

'  The  term  acid-fast  is  applied  to  nrpani.sms  ffsistinjj  dfcolorizalion  bv 
acids.  A  full  review  of  these  orjjanisms  will  be  found  in  a  paper  by  Roscnbcrecr. 
"Medicine,"  March,  1904;  also  "Publications  from  the  Laboratories  of  the  Jef- 
ferson Medical  College  Hospital,"  vol.  i,  1904. 

*  See  Rosenbergcr,  "Publications  from  the  Laboratories  of  the  JcfTiTson 
Medical  College  Hospital,"  1904,  vol.  i;  also  Arloing  and  Courmont,  "Boston 
Med.  and  Surg.  Jour.,"  1904.  vol.  cli. 

'  An  excellent  review  of  this  organism  is  given  by  Moore,  "Jour.  Med.  Re- 
search," May,  1904,  p.  521. 

*  For  studies  of  the  tubercle  bacillus  in  cold-blooded  animals  see  Dubard. 
"Revue  de  la  Tubcrculose."  1898.  vol.  vi.  n.  13:  Bataillon.  Dubard  and  Terre. 
"Zeit.  f.  Tub.,"  1902,  vol.  iii,  p.  467:  Sibley,  "Trans.  Path.  See.  of  London." 
1S92,  vol.  xliii,  pp.  189  and  426;  Hanscmann.  "Centralbl.  f.  Bakt.."  1903,  xxxiv. 
p.  212,  also  Friedmann,  "Deu'    .iied.  Woch.."  Jan.  28,  1904,  No.  5,  p.  166. 


148  GENERAL    PATHOLOGY. 

that  they  are  closely  related  strains.  Practically  all  warm-blooded 
animals  may  be  infected  with  tubercle  bacilli;  some,  however,  are  much 
more  susceptible  than  others;  the  ass  and  the  goat  are  much  more 
resistant  than  the  horse  or  cow.  In  man  the  disease  is  exceedingly 
prevalent.  In  Germany  during  1894  diphtheria  and  croup,  whooping- 
cough,  scarlet  fever,  measles,  and  typhoid  gave  a  total  mortality  of 
116,705;    tuberculosis,  123,904. 

Susceptibility. — Mortuary  statistics  go  to  show  that  practically  all 
adults  have  at  some  time  harbored  the  tubercle  bacillus.  The 
fact  that  a  large  number  escape  the  ravages  produced  by  the  organism 
clearly  indicates  that  those  who  succumb  must  offer  less  resistance  to  the 
inroads  of  the  infection  than  those  who  survive.  Exactly  what  deter- 
mines this  increased  susceptibility  is  not  known.  Children  of  tuberculous 
parents  are  clearlv  more  susceptible  than  those  having  a  healthy  parent- 
age. Overcrowding,  bad  sanitary  conditions,  and  dust  occupations 
undoubtedly  favor  the  occurrence  of  the  infection. 

Paths  of  Infection. — Prenatal  Tuberculosis. — Tubercle  bacilli  have 
been  demonstrated  in  the  semen  of  tuberculous  animals,  including  man, 
and  it  is  equally  possible  that  the  ovum  might  contain  the  bacilli; 
proof,  however,  of  conceptional  tuberculosis  is  not  conclusive,  although 
the  possibilitv  must  be  admitted.  Transplacental  injection  has  been 
proved  experimentally  in  the  lower  animals  and  also  observed  in  man ; 
Auche  and  Chambrelent  ^  have  been  able  to  find  twent}'  reported  in- 
stances in  which  infection  took  place  through  the  placenta,  which, 
whenever  examined,  has  been  found  infected.  - 

Inoculation  tuberculosis  is  seen  in  the  postmortem  nodule,  verruca 
necrogoiica  of  Wilks.  The  author  has  had  an  opportunity  to  observe  a 
rather  extensive  local  tuberculosis  of  the  tendon-sheaths  of  the  hand  and 
wrist,  resulting  from  infection  of  an  open  wound  upon  the  thumb;  the  pa- 
tient had  nursed  a  son  suffering  from  pulmonary  tuberculosis,  and  during 
his  illness  had  accidentally  wounded  her  thumb.  The  wound  was  slow  to 
heal,  and  even  before  its  disappearance  tuberculosis  of  the  adjacent 
tendon-sheath  developed;  later  the  infection  extended  to  a  number  of 
tendons  in  the  wrist,  eventually  following  the  course  of  these  structures  in 
both  the  dorsal  and  palmar  tissues.  Ware^  has  been  able  to  collect  21 
cases  of  inoculation  tuberculosis  following  ritual  circumcision,  and 
Bruns  "*  reported  four  instances  of  cutaneous  inoculation  bv  the  hypo- 
dermic needle.  Ravenel  '"  has  collected  the  recorded  instances  of  in- 
oculation of  man  by  bovine  bacilli. 

Inhalation  Infection. — It  is  the  consensus  of  opinion  that  tubercle 
bacilli  most  commonly  enter  the  system  with  the  inhaled  air;  in  this 
way  infection  may  reach  the  nose,  tonsils,  pharynx,  larynx,  trachea, 
bronchi,  and  lungs.  Infection  through  the  nasal  mucosa  must  be 
rare;  oral  and  laryngeal  infection  will  be  again  referred  to  when  dis- 
cussing food  infection.  Kingsford,**  studying  tuberculosis  in  children, 
thought  that  49  per  cent,   of  his  patients   were  infected  through  the 

*  "Arch,  de  Med.  Exp.,"  1889,  xi,  p.  521. 

^  See  Giepel,  "Miinch.  med.  Woch.,"  Sept.  20,  1904,  p.  1676,  on  "Tubercu- 
losis of  the  Human  Placenta." 

2  "N.  Y.  Med.  Jour.,"  Feb.  26,  189S. 
^  "Miinch.  med.  Woch.,"  Sept.  13,  1904. 

*  "Proc.  Path.  Soc.  of  Phila.,"  May,  1902,  p.  iSi. 
^  "Lancet,"  Sept.  24.  1904.  p.  S89. 


HACTKKIA    AS   CAUSKS  ol'   DISEASK.  1  49 

mucosa  of  the  trachea  or  hirjjer  bronchi.  Anatoniii-  stu<hes  k<»  to  show 
that  the  pulmonary  tissues  are  more  commonly  affected  in  this  wav  than 
are  the  larger  bronchi,  trachea,  or  larynx. 

Iiiiicstioii  Tnhcrc itlos is. —^Inhaled  tubercle  bacilli  must  IreiiuciUlv 
be  deposited  upon  the  oral  and  pharyngeal  mucosa  and  on  the  tonsil,  and 
to  these  must  be  added  organisms  entering  with  the  food.  There  can 
be  no  doubt  that  bacilli  may  reach  the  cervical  glands  from  lesions  in 
the  mouth  or  from  the  tonsils  and  pharynx.  The  frequency  with  which 
tuberculosis  attacks  the  cervical  lymph-nodes,  ])articularly  in  child- 
hood and  adolescents,  argues  strongly  for  this  route  of  infection.  Kings- 
ford  '  from  the  tonsils  of  i  7  children  found  evidence  of  tuberculosis  in 
7.  although  in  only  one  of  these  was  there  reason  to  l)elieve  that  the 
tonsillar  lesion  might  be  primary.  Infection  through  the  esophagus  and 
stomach  is  rare.  With  regards  to  the  frequency  of  intestinal  infection 
there  has  been,  within  recent  years,  the  warmest  controversy.  Certainly 
primary  intestinal  tuberculosis  is  rare.  Behring^  strongly  contends 
for  infection  through  the  intestine,  holding  that  it  is  not  necessar)'  to 
prove  a  primary  lesion  of  the  mucosa,  although  this  may  have  been 
present.  Ravenel,^  Dobroklonski,^  and  Bisanti  and  Pansiet  '  have 
shown  that  in  animals  tubercle  bacilli  may  pass  through  an  intestinal 
mucnsa  in  which  there  is  no  demonstrable  lesion." 

Morbid  Anatomy  of  Tuberculosis. — In  order  that  the  tubercle  bacillus 
may  produce  its  characteristic  lesions  the  organism  must  pass  the 
epithelial  barriers  and  enter  the  connective  tissues.  The  exception  to 
this  general  statement  is  found  when  the  organism  colonizes  on  epi- 
thelial surfaces,  for  example,  the  mucosa  of  the  middle  ear,  the  pul- 
monary air  vesicles,  or  in  the  Fallopian  tubes.  When  growing  in  such 
locations,  the  bacillary  products  promptly  incite  a  reactive  inflamma- 
tion accompanied  by  accumulation  of  the  leukocytes,  necrosis  of  the 
overlying  epithelium,  and  caseous  changes  in  the  exudate.  Unless 
promptly  circumscribed  the  extending  necrosis  exposes  the  connective 
tissue  into  which  the  bacillus  enters,  giving  rise  to  a  characteristic- 
lesion — the  histologic  tubercle.  This  structure — ordinarily  called  a 
miliary  tubercle— is  primarily  an  accumulation  of  cells  derived  largely 
from  the  blood  and  adjacent  lymph-spaces.^  The  tubercle  bacillus 
both  dead  and  living  exerts  a  strong  chemiotactic  power  on  the  mononu- 
clear leukocytes;  deposited  in  the  tissues,  an  accumulation  of  these 
cells  rapidly  forms  around  the  organism.  There  soon  a|)pear  in  the 
mass,  cells  much  Jarger  than  the  lymphoid  elements,  about  the  origin 
of  which  there  is  less  certainty.  Some  hold  that  they  are  derived  from 
mononuclear  leukocytes,  others  from  the  endothelium  of  the  blood- 
vessels, or  from  the  connective-f''^-'!<'  ■■'>H<      Tt  is  iirdb.-iblr-  that   thc\ 

'    "Lancet."  Jan.  g.  1904,  p.  Sq. 

-  For  recent  papers  supporting   Brhring's  vi.  Hcitzke,    "Bim 

\V<>ch.."  Jan.  0.  1905. 

'    Jour.  Med.  Research."  Dec.  IQ03.  p.  460. 

'    "Arch,  de  med.  Exp.,"  March  i.  1890.  p.  253. 

'  ■Soc.  dc  Biol.."  Jan.  28,  1905. 

•  For  further  discussion  of  infection  path«!  in  ttiSerculosis  «•«•  Wassermann. 
•  Berl.   klin.   Woch.."    Nov.   28.    1904:     Bart' '        "V  klin.    W     '  'i.ril    14. 

IQ04;  and  Fischer.  "Munch,  med.  Woch  ."  At:  i. 

'See  Miller.  "Jour,  of  Path,  and  Bact  -  ;  

"Histopenesis  of  the  Tulxrclc." 


GENERAL    PATHOLOGY. 


are  of  leukocytic  origin.  Near  the  center  of  the  young  tubercle,  giant 
cells  are  the  next  conspicuous  structures  observed.  These  var}-  in 
size,  but  may  attain  a  maximum  diameter  of  75  !j-  .  In  the  typical 
cell  of  this  kind  the  remaining  nuclei  are  peripherally  distributed  and 
the  center  of  the  cell  granular,  while  from  its  margin  spiculated  ex- 
tensions project  among  the  adjacent  cells.  By  appropriate  methods 
tubercle  bacilli  in  varying  numbers  can  be  found  in  its  interior.  With 
regard  to  the  origin  of  these  structures,  two  views  are  held:  (i)  Thev 
result  from  confluence  of  the  epithelioid  cells  and  increase  in  size  bv 
the  continued  merging  of  these  elements.  (2)  It  is  not  impossible  that 
some  of  the  giant  cells  are  derived  from  proliferated  endothelial  or  fixed 
connective-tissue  cells,  in  which  the  nuclei  have  divided  without  divis- 
ion of  the  protoplasm.  Miller  is  strongly  inclined  to  the  origin  first 
suggested.  Within  the  developing  tubercle  there  is  usually  demon- 
strable a  reticulum  which  is  more  conspicuous  in  some  places  than 
in  others.  Miller  believes  that  it  represents  prolongations  of  con- 
nections between  the  original  cells 
of  the  tubercle, — a  view  long  ago 
advanced  by  Rindfleisch,  and  which 
best  explains  its  general  characters. 
It  is  possible  that  part  of  the  re- 
ticulum is  residual  connective  tissue 
that  has  not,  as  yet,  disappeared 
under  the  influence  of  the  bacillary 
toxins.  With  regard  to  the  non- 
cellular  constituents  of  the  tubercle, 
fewer  accurate  data  are  obtainable. 
In  young  tubercles  it  may  be  possi- 
ble to  demonstrate  the  presence  of 
fibrin,  and  this  is  usually  considered 
an  evidence  of  coagulation  necrosis. 
The  mass  just  described  varies  in 
size,  being  rarely  larger  than  a  pin- 
point (one  or  two  millimeters),  al- 
though it  may  be  much  larger;  as  a 
rule,  a  number  of  these  develop  con- 
jointly, and  become  confluent.  The  tubercle  large  enough  to  be  seen  bv 
the  unaided  eye  contains,  as  a  rule,  many  small  tubercles,  such  as  that 
described.  By  the  changes  already  noted,  the  capillary  blood-supply  is 
cut  oft'  from  the  center,  favoring  the  occurrence  of  necrotic  and  degenera- 
tive processes  brought  about  by  the  specific  action  of  the  bacillus,  or,  more 
properly,  of  the  bacillary  products.  Coagulation  necrosis  terminates  in 
solidification  of  any  Hquid  exudate  the  product  of  which,  with  the  dead 
cells,  proceeds  to  caseation.  In  the  beginning  of  this  process  granular  and 
fatty  changes  occur  in  the  cell  protoplasm,  the  cell  outlines  become  in- 
distinct or  disappear,  and  the  nuclei  shrivel  and  disintegrate;  the  nuclear 
fragments  often  retain  their  affinity  for  basic  dyes  long  after  the  struc- 
turally perfect  cell  has  disappeared.  The  caseous  area  produced  by  the 
foregoing  changes  may  follow  the  peripheral  extension  of  the  process 
until  two  or  more  tubercles  join  by  confluence  into  the  formation 
of  a  single  mass.  Caseation  may  be  accompanied  by  liquefaction, 
coagulation,  or  hyaline  necrosis;   eventually,  the  mass  is  converted  into 


Fig.  83. — Diagram  of  the  Structure  of  a  Tuber- 
cle; A  Purely  Theoretic  Idea,  Rarely 
Demonstrated. — (Gottld.) 


n.\(   IKKIA    AS   CVrSKS  ol-    DISEASK. 


i5» 


a  yellowish  nodule  of  structureless  detritus, the  so-called  yellow  tubercle; 
prior  to  the  stage  of  softening  the  mass  was  referred  to  as  a  gray  tubercle  ; 
where  a  number  of  these  run  together,  tlie  collection  shows  a  decided 
tendency  to  evacuate  itself  hy  discharge  through  the  most  feasible 
route,  leaving  behind  a  cavity  or  ulcer.  If  not  in  all,  certainly  in  a 
large  percentage  of  the  cases,  dissolution  of  the  tubercle  is  brought 
about  through  a  secondary  infection  by  the  organisms  of  suppuration. 
The  tuberculous  ulcer  and  abscess  are  more  commonly,  particularlv 
in  the  respiratory  organs,  hastened  to  their  full  development  bv  the 
added  pyogenic  invasion.  This  terminates  the  process  of  softening,  and 
is  an  unfavoral)le  ending  of  the  tuberculous  lesion. 

Cured  and  Healed-in,  Latent,  or  Quiescent  Tuberculosis. — Grancher' 
found  that   m   Syf)  cliildrcii,    141    maniteslcd  unniistakalile  evidence  of 


>Cr;^^T-^V^^w,     '^ 


Fig.  84. — AccTE  Disseminated  Tc'sercolosis  of  the  Lu.ng— (5iAwjuj.)     X40  dianieierj. 
a.  Tubercle  undergoing  caseation.    Just  below  the  letter  b  are  two  tubercles:    the  one  on  the  left  contain}  three 
giant-cells;   the  one  on  the  right    shows   beginninu    caseation.     6i.  '■i-    Tubercles,     e.    Nodule  cootAiniOK 
at  least  four  tubercles;  two  show  beginning  caseation  and  two  cont.-un  giant-cells,     d.    Alveolus.     To  the  left 
of  e  is  a  blood-vessel.     /.   .\rea  of  beginning  caseation.     Other  tubercles  are  also  shown. 

latent  ganglio-pulmonary  tuberculosis.  Mortuary  statistics  by  careful 
observers  show  that  a  careful  postmortem  examination  reveals  evidences 
of  healed-in  or  cicatrized  tuberculous  lesions  in  from  eighty-five  to 
ninety  per  cent,  of  all  cadavers  examined.  In  most  cases  the  tubercu- 
lous nodule  is  of  the  caseous,  calcareoca.seous.  or  fibrocaseous  tvpe:  less 
commonlv  it  is  fibrous.  There  can  be  no  doubt  that  tuberculous  inflam- 
mation of  the  peritoneum,  pleura,  and  meninges  may  completely  recover, 
often  leaving  no  healed-in  or  latent  area  of  quiescent  infection.  When 
colonization  of  the  l)acillus  is  widely  disseminated  in  an  organ  the 
process  is  rarely  arrested,  but  even  extensive  infiltration  is  sometimes 
suppressed;  with  Prof.  Hearn  and  Dr.  Thornton,  at  operation,  I 
case  of  tuberculous  peritonitis  the  bacterial  nature  of  which  was 
'  •'Bull,  de  I'Acad.  de  Med.  Paris."  Ixviii,  No.  25. 


152  GEXERAL    PATHOLOGY. 

lished  by  examination  of  excised  portions;  beneath  the  hepatic  capsule, 
wherever  the  Hver  was  exposed,  innumerable  tubercles  were  present; 
the  patient,  however,  made  an  eventual  recovery.  Spengler  ^  reports 
an  instance  of  healed  miliary  tuberculosis  of  the  lungs.  These  organs 
contained  numerous  small,  dense  nodules  of  scar  tissue,  a  few  necrotic 
foci,  but  neither  giant  cells  nor  bacilli.  The  common  impression  that 
tuberculosis  is  an  incurable  disease  has  long  been  shown  to  be  incorrect, 
and  it  is  now  generally  accepted  that  a  very  large  percentage  of  the 
infected  fully  recover.  When  recovery  does  not  take  place,  there  is  not 
infrequently  more  or  less  successful  effort  at  local  limitation  of  the 
infection.  In  favorable  cases  this  is  brought  about  by  the  production  of 
a  dense  wall,  through  which  any  fluid  that  results  from  the  degenerative 
changes  may  be  partly  absorbed,  leaving  behind  the  caseous  detritus, 
containing  not  uncommonly  tubercle  bacilli ;  into  the  fil:)roid  capsule 
and  caseous  material  calcareous  infiltration  may  occur,  forming  a 
stone-like  mass,  in  which  the  tuberculosis  virus  may  be  destroyed  or 
indefinitely  stored.  Sometimes  the  fibroid  change  (fibrosis)  may  be 
conspicuous  and  the  calcareous  infiltration  but  slight ;  in  other  in- 
stances the  calcific  matter  may  obscure  the  whole  mass.  The  tubercle 
bacilli  contained  within  such  nodules  may  retain  their  viability,  and 
hence  their  pathogenicity,  or,  in  the  course  of  time,  mav  be  no  longer 
demonstrable.  At  first  the  organism  stains  with  its  characteristic 
activity — a  reaction  that  becomes  less  and  less  manifest,  and  eventuallv 
disappears,  so  that,  in  old  tubercles,  under  suitable  conditions,  the 
organism  may  be  destroyed,  or  at  least  not  demonstrable,  and  the 
degenerated  contents  of  the  mass  may  be  no  longer  infective.  During  the 
later  stages  in  the  development  of  this  bodv  it  is  known  as  a  quiescent 
tubercle  or  tuberculous  area.  Such  "healed-in"  tubercles  may  remain 
inactive  or  may,  if  they  contain  viable  bacilli,  manifest  recrudescence. 
The  length  of  time  during  which  the  bacilli  retain  their  pathogenic 
activity  can  never  be  foretold;  therefore,  a  quiescent  tuberculous  area 
must  always  constitute  a  menace  to  health,  as,  under  favorable  con- 
ditions, the  bacilli  may  at  any  time  be  rapidly  disseminated,  giving  rise 
to  miliary  tuberculosis. 

Other  Anatomic  Divisions  of  Tuberculosis. — When  the  infection  is 
restricted  to  a  small  area,  it  is  called  localized  tuberculosis.  If  miliary 
tubercles  are  scattered  through  an  organ,  the  condition  is  one  of  miliary 
tuberculosis  of  the  organ  involved;  for  example,  miliary  tuberculosis 
of  the  lung,  miliary  tuberculosis  of  the  liver,  etc.  If  the  bacilli  have 
been  widely  distributed  through  the  body,  many  organs  containing 
characteristic  tubercles,  the  condition  is  called  general  miliary  tuber- 
culosis. Chronic  caseous  tuberculosis  is  that  form  in  which  confluence 
of  tubercles  and  extensive  caseation  give  rise  to  cheesy  masses  which 
may  be  large  or  small.  When  such  caseous  areas  discharge  their  con- 
tents on  the  surface  or  into  one  of  the  body -passages  communicating 
with  the  exterior  and  permitting  escape  of  the  cheesy  material,  the  term 
cJiroiiic  ulcerative  tuberculosis  is  used.  The  last  is  the  form  frequently 
present  in  the  lung,  where  it  gives  rise  to  excavations  called  cavities.  In 
some  cases  the  evolution  of  the  disease  is  associated  with  the  pro- 
duction of  a  large  amount  of  fibrous  tissue, — a  condition  called  chrome 
fibroid  tuberculosis.  A  less  frequent  type  of  tuberculous  infection,  involv- 
^  "Zeit.  f.  Hyg.  u.  Infectkrank.,"  1904,  xlvii.  p.  1^3. 


BACTERIA    A>   I  Al   >i;>  OF   DISKASK.  i  •,  > 

ing  particularly  the  intestine  in  the  neighhorhood  oi  the  ileoceial  valve. 
but  also  occurring  in  the  larynx  and  on  the  serous  memhranes,  is  known 
as  chronic  hypcrf^Uistic  tithcrcnlosis.*  in  this  form  a  large  amount  of 
fibrous  tissue  is  produced  often  without  any  caseation  and  contaming 
but  few  tubercle  bacilli.  The  enormous  increase  in  hbrous  tissue  is 
shown  bv  the  fact  that  the  intestinal  wall  may  be  i  cm.  or  even  2  cm. 
in  thickness.  Stenosis  of  the  larynx,  intestine,  or  other  tube  may  result 
from  the  formation  of  such  masses.  Surgeons  have  found  that  this  type 
of  tuberculosis  yields  to  treatment  l)y  excision,  which  often  results 
in  a  cure.  Histologically  the  tissue  is  composed  of  fibrous  and  fibro- 
hyaline-elements  containing  perivascular  accumulations  of  lymphoid 
cells;  giant  cells  are  frequently  absent  and  tubercle  liacilli  scanty  and 
difficult  to  demonstrate. 

The  name  tuhcrcitlonia  has  been  ajjplied  to  more  or  less  perfectly 
circumscribed  masses  of  granulation  and  hyaline  fibrous  tissue  often 
possessing  a  structure  closely  resembling  the  gumma  of  syjihilis.  I  be- 
lieve that  this  form  of  tuberculosis  is  nothing  more  than  a  nodular  type 
of  the  hyperplastic  lesion.  The  histology  of  the  two  conditions  is 
strikingly  similar.  Tuberculomas  are  found  particularly  in  the  larynx, 
but  are  occasionally  encountered  Ijeneath  the  nasal  mucosa  and  some- 
times in  the  viscera.  1  have  seen  such  a  nodule  in  the  heart,  although 
in  that  location  thev  are  rare.  Some  writers  speak  of  chronic  caseous 
collections  as  tuberculomata;  the  term,  however,  should  be  restricted 
to  the  type  of  lesion  just  described. 

Secondary  Infection  in  Tuberculosis. — In  ordinary  forms  of  tuber- 
culosis the  symptoms  are  largely  due  to  pyogenic  infection  of  tubercu- 
lous areas;  this  is  especially  true  of  chronic  caseating  lesions  associated 
with  the  formation  of  cavities  or  ulcers.  The  character  of  the  infection 
has  been  especially  investigated  by  Sata,-  Ophiils.''  Weismayr.*  Oes- 
tern,'  Petroff."  and  Bruns";  the  organisms  chiefly  found  have  been 
the  white  and  vellow  staphylococci  and.  in  the  lungs,  streptococci,  pneu- 
mococci.  influenza  bacilli,  "tetracocci,  and  less  commonly  mould  fun^i. 
Bv  the  introduction  of  additional  bacteria,  tissue  necrosis  is  rapidly 
extended  and  the  systemic  poisoning  produced  l>y  the  absorption  of 
microbic  poisons  proportionately  increased.  Under  suitable  conditions 
saprophytic  organisms  may  infiltrate  the  necrosing  tissues,  hastening 
liquefai  tion  and  a-Ming  their  quota  of  absorbable  toxins. 

Extension  of  Tuberculosis.— Tuberculosis  develops  as  an  initial  lesion. 
inoculation,  or  point  of  primary  invasion,  from  which  local  or  general 
extension  mav  occur.  The  necessity  of  a  recognizable  initial  lesion  is 
not  always  to  be  insisted  uj)on.  for' when  a  guinea-pig  is  fed  tubercle 
bacilli,  infection  of  the  Ivmph-nodes  of  the  mesentery  may  occur 
without  any  recognizable  focus  in  the  alimentary  canal.  Tuberculosis 
of  the  mesenteric  nodes,  as  seen  in  children,  is  similarly  ex[)lained.  par- 
ticularly when  we  take  into  consideration  the  frequency  with  which 
milk  contains  tubercle  bacilli.     The  local  tuberculous  le^-.n  .....n  ,n  th.- 

'  Sec  Tuberculosis  of  the  Intestine. 

=  •Zieijler's  Bcitrapc."   iSgg.  Supplement. 

^  •  Airier.  ]out.  Med.  Sci.,"  igoo. 

'    "Zcit.  f.'Hcilk."  Bd.  xxii.  iqoi.  •      •   •      , 

''  '  Centralbl   f    Bakt..'  x.xxvii,  review  of  literature  and  onginal 

•  'Ann.  dcl'bist.  Pasteur."  .Aug.  23.  1004 

"    'Deut.  Zeit.  f.  Chir..'"  i<jo4.  Bd  Ixxv. 


154  GENERAL   PATHOLOGY. 

lymph-nodes  of  the  neck  must  have  resulted  from  infection  through 
the  oral  cavity,  possibly  the  tonsil,  without  there  having  been  any  history 
to  indicate  a  past  or  associated  initial  lesion  of  the  mucous  membranes 
at  the  point  of  ingress.  The  possibility,  however,  of  superficial  initial 
lesions  has  already  been  pointed  out.  (See  p.  148.)  Tubercle  bacilli 
may  enter  the  body  without  the  production  of  any  recognizable  super- 
ficial lesion.  The  occurrence  of  tuberculosis  of  the  body  of  a  vertebra, 
or  of  primary  tuberculosis  of  a  joint,  without  other  evidences  of  the 
disease,  indicates  such  a  possibility.  The  fact  that  a  local  lesion  is 
not  produced,  and  that  bacilli  may  apparently  pass  into,  and  travel  by, 
the  circulation,  eventually  inducing  tuberculosis  in  distant  parts,  indi- 
cates that  the  induction  of  a  primary  tuberculous  nidus  is  dependent 
upon  factors  other  than  the  mere  presence  of  tubercle  bacilli.  These 
factors  are  probably  the  lessened  resistance  of  certain  tissues,  or,  we 
might  say,  greater  susceptibility,  and  the  occurrence  of  points  of  least 
resistance.  The  latter  may  be  produced  by  associated  lesions  or  by  injury. 
The  fact  that  certain  tissues  possess  a  higher  degree  of  susceptibility  to 
tuberculosis  is  indicated  by  the  frequency  with  which  the  disease  occurs 
in  the  lungs,  bone,  and  lymph-nodes.  The  presence  of  such  heightened 
susceptibility  also  indicates  a  relative  immunity  in  other  tissues:  for 
example,  the  muscles,  in  which  typical  tuberculous  lesions  are  rare. 
From  the  initial  or  primary  lesion  propagation  may  occur  by  one  of  the 
following  routes  ; 

I .  By  the  Blood. — The  wide-spread  dissemination  of  tubercles  neces- 
sarily implies  that  the  organisms  have  been  transported  by  the  circulat- 
ing blood. ^  The  initial  lesion  from  which  the  bacilli  are  poured  into 
the  circulation  may  be  a  tuberculous  endangeitis  {endo phlebitis  or  en- 
darteritis tuberculosa)  due  to  the  production  of  a  cheesy  nodule  in  the 
vessel  wall,  probably  through  infection  by  the  vasa  vasorum.  In  other 
cases  the  bacilli  may  be  implanted  directly  on  the  intima,  or,  less  com- 
monly, on  the  endocardium  including  the  valve  leaflets.  Growing  in  such 
locations,  hematogenous  dissemination  is  to  be  expected.  The  initial 
lesion  may  be  in  the  tJioracic  duct,  which  can  be  infected  by  bacilli  travers- 
ing its  lumen  or  from  mesenteric,  retroperitoneal,  or  mediastinal  lymph- 
nodes,  either  by  drainage  from  these  structures  or  by  erosion  of  a  caseous 
node  through  the  duct.  A  caseous  lymph-node  in  the  lung  or  elsewhere 
or  a  primary  focus  in  bone  may  discharge  its  contents  into  a  vein,  or, 
less  commonly,  an  artery.  In  a  study  of  1 23  cases  of  acute  miliary  tuber- 
culosis Schmorl  found  that  the  largest  percentage  arose  from  erosion  of 
vessels  by  contiguous  caseous  lymph-nodes ;  in  5  cases  he  observed  tuber- 
culous nodules  in  atheromatous  ulcers.  Tubercle  bacilli  may  be  present 
in  the  circulation  in  sufficient  numbers  to  be  demonstrated  in  drawn 
blood,  constituting  a  true  tubercnlous  bacillemia  or  septicemia. 

Dissemination  of  tubercle  bacilli  by  means  of  the  blood  usually  results 
in  the  wide-spread  distribution  of  the  germ,  followed  by  an  eruption  of 
numerous  tubercles  in  various  organs.     Such  a  condition  is  called  general 

^  See  recent  papers  by  Benda,  "Berl.  klin.  Woch.,"  1899,  Nos.  26,  27,  and  29; 
Landsteiner  and  Mucha,  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.,"  Sept.  30, 
1904;  Silbergleit,  "Virch.  Arch.,"  Feb.  i,  1905,  Bd.  179,  p.  283;  and  Forssner, 
"Centralbl.  f.  allg.  Path.  u.  path.  Anat.,"  1905,  Bd.  xvi,  No.  7.  Longcope  has 
recently  reported  dissemination  secondary  to  tuberculosis  of  the  thoracic  duct; 
the  paper  will  appear  in  the  Report  of  the  Ayer  Clinical  Laboratory  of  the  Penn- 
sylvania Hospital,  vol.  iii. 


BACTKKIA   AS  CAUSKS  OK   DlSlvASK. 


iiiiluirv  tiibi-rcnlosis  and  is  associated  with  more  or  less  marked  febrile 
and  other  toxic  ])henomena.  In  such  cases  not  only  do  the  viscera  sutTer, 
but  infection  of  one  or  more  serous  membranes,  especially  the  meninj,'cs, 
is  not  infretiuently  present.  The  tubercles  rarely  attain  any  consider- 
able size,  as  the  patient  usually  dies  before  sullicicnt  time  hasehqjscd.  In 
other  instances  the  amount  of  infectious  material  disseminated  was  cvi- 
dentlv  small,  giving  rise  only  to  a  few  tubercles  scattered  here  and  there 
through  the  viscera.  Under  such  circumstances  the  jjatient  may  survive 
long  enough  for  the  tubercles  to  attain  considerable  size,  and  even  to 
caseate.  Whenever  there  is  a  general  miliary  tuberculosis  such  as  just 
indicated,  there  is  reason  to  believe  that  a  primary  caseous  nodule  has 
communicateil  in  some  way  with  the  general  circulation.  Often  a  most 
careful  postmortem  will  fail  to  show  the  primary  lesion.  The  author 
recalls  a  case  of  general  miliary  tul)erculosis  involving  nearly  all  the  vis- 
cera, in  which  a  most  thorough  search  was  about  to  be  abandoned  when 
the  primarv  nodule  was  discovered  in  the  anterior  part  of  the  body  of  a 
dorsal  vertebra.  Subsequent  inquiry  elicited  the  fact  that  the  patient 
had,  a  few  weeks  before  admission  to  the  hospital,  encountered  a  severe 
fall,  which  strained  his  back,  and  to  which  he  attributed  his  illness. 
The  slight  inflammatory  changes  that  surrounded  the  nodule  indicated 
that  possibly,  indeed  probably,  the  injury  had  caused  the  caseous 
area  to  break  into  the  surrounding  cancellous  bone  and  favored  the 
dissemination  of  the  contained  infectious  matter.  The  possibility  of 
disseminating  tubercle  through  the  blood-stream  as  the  result  of  m- 
complete  operative  procedure  has  been  pointed  out  by  many  surgeons. 
The  breaking  up  of  a  tuberculous  area,  without  at  the  same  time  com- 
pletelv  eradicating  infection,  may  be  followed  by  general  dissemination 
of  the  poison,  miliary  tuberculosis,  and  death. 

2.  Another  means  of  extension  is  by  the  lymph-stream.  This  is  mani- 
fested in  the  tul)erculous  lvm]^h-nodes  of  the  neck  in  children,  which  result 
from  infection  through  the  tonsils  and  through  diseases  of  the  teeth,  gums, 
and  oral  mucosa ;  the  same  method  of  spread  is  shown  by  the  occurrence  of 
tuberculous  processes  in  the  structures  along  the  course  of  the  lymph- 
stream,  in  tuberculous  ulceration  of  the  intestine.  Infection  from  the 
thoracic  duct,  referred  to  above,  might  with  propriety  be  included  with 
this  group. 

3.  In  addition  to  the  Ivmph  and  blood,  the  bacdli  may  follow  the 
course  of  other  fluids.  Thus,  tuljerculosis  of  the  ahmentan.'  canal  may 
be  secondarv  to  tuberculosis  of  the  respiratory  passages,  and  may  be  due 
to  swallowing  bacilli-laden  sputum;  tuberculosis  of  the  bladder  or 
tuberculous  abscess  of  the  perineum  may  be  secondary  to  tuberculosis 

of  the  kidnev. 

4.  Locallv.  tuberculosis  mav  spread  by  continuity  or  continuity  ot 
tissue;  this  mav  occur  even  against  the  ordinary  course  of  fluid  cur- 
rents, as  in  tuberculosis  of  the  ureter,  which  may  be  secondary  to  tuber- 
culosis of  the  bladder;  tuberculosis  of  the  prostate  may  be  secondary 
to  tuberculous  processes  in  the  rectum  or  in  other  contiguous  structures : 
tuberculosis  of  the  intracranial  tissues  may  be  due  to  extension  ot 
tuberculosis  from  the  middle  or  internal  ear,  mastoid  cells,  or  frontal 

sinuses.  .  e  •   c    ».- 

Site  of  Tuberculosis.— One  of  the  most  common  points  of  infection  is 
the  lung;  following  this  in  frequency,  tuberculous  affections  of  the  joint-. 


156  GENERAL    PATHOLOGY. 

bones,  and  lymph-nodes  are  next  in  order;  these  are"  followed  bv  tubercu- 
losis of  the  mucous  membranes  other  than  the  lungs,  tuberculosis  of  the 
serous  memljranes,  tuberculosis  of  the  skin,  tuberculosis  of  the  spleen, 
tuberculosis  of  the  liver,  tuberculosis  of  the  brain,  tuberculosis  of  the 
generative  organs,  and  tuberculosis  of  the  heart  and  voluntarv  muscles, 
in  about  the  order  given. 

Tuberculosis  of  the  organs  is  further  considered  in  Part  III.  The 
only  form  of  local  tuberculosis  that  will  be  described  at  this  point  is 
lupus. 

Tuberculosis  of  the  Skin  (Lupus).' — This  condition  usually  begins 
as  a  lymphoid  infiltration  following  the  course  of  the  vascular  loops 
m  the  corium.  The  process  slowly  extends  by  the  development  of 
outlying  tubercles  that  coalesce  with  the  olde'r  nodules.  The  fullv 
formed  tubercle  in  lupus  may  be,  and  indeed  usually  is,  structurallv 
identical  with  tubercles  seen  elsewhere.  Sometimes  the  miliary  tubercle 
in  the  skin  is  quite  atypical,  and  in  the  absence  of  the  bacilli  a  satis- 
factory diagnosis  can  not  be  made.  In  the  ulcerative  form  of  lupus 
(lupus  exedens)  the  coalescence  of  tubercles  in  the  corium,  and  even 
for  some  distance  in  the  subcutaneous  tissue,  associated  with  the  oblitera- 
tive  changes  in  the  capillaries  followed  by  caseation,  leads  to  necrosis 
of  the  overlying  derma  and  the  formation  of  an  ulcer.  Occasionallv, 
superficial  necrosis  does  not  occur,  and  hence  ulceration  is  absent.  In 
such  cases  the  infiltration  commonly  shows  more  fibrous  tissue  than 
in  the  ulcerative  form  of  the  lesion;  the  skin  is  slightly  raised,  and  is 
usually  somewhat  more  adherent  than  normal;  occasionally,  outlines 
of  caseous  masses  can  be  detected  beneath,  even  when  superficial  ne- 
crosis does  not  follow.  This  form  of  cutaneous  tuberculosis  is  known  as 
lupus  nonexedens.  It  is  probable  that  cutaneous  tuberculosis  results 
from  local  inoculation;  the  author  has  seen  one  well-marked  and  pro- 
tracted case  of  lupus  that  followed  vaccination,  and  two  cases  of 
extensive  cutaneous  tuberculosis  in  which  the  lesions  followed  the  appli- 
cation of  the  actual  cautery,  the  ulcerative  process  having  been  pur- 
posely prolonged  for  its  so-called  alterative  action.  Lupus  is  a  particu- 
larly chronic  and  intractable  disease,  and  may  be  associated  with,  or 
followed  by.  more  general  tuberculous  dissemination. 

Pseudo-tuberculosis-  includes  a  number  of,  probably  manv,  infectious 
processes,  usually  subacute  or  chronic,  characterized  by  the  production  of 
tubercles  which  macroscopically  and  microscopically  may  be  almost,  if 
not  quite,  indistinguishable  from  similar  structures  re.-=ulting  from  infec- 
tion by  the  tubercle  bacillus.  A  large  number  of  organisms  entering 
the  tissue  in  man  and  certain  lower  animals  are  endowed  with  this 
property.  Not  only  do  such  germs  produce  tubercles,  but  often  the 
morphology  and  stain  reaction  of  the  microbe  so  closely  resemble  the 
tubercle  bacillus  that  differentiation  becomes  extremely  difficult.     Cer- 

1  For  recent  papers  on  tuberculosi.s  of  the  skin  see  Hartzell.  "Amer.  Med.." 
July  2.  1904,  also  Jtiliusberg,  "Mitthcihrngen  a.  d.  Grenzegebieten  d.  Med.  it. 
Chir.."  1904.  Bd.  13,  Heft  4  and  5. 

2  See  works  referred  to  in  foot-note,  p.  81 .  The  earlier  literature  will  be  found 
m  Muir's  article.  "Jour,  of  Path,  and  Bact.."  May,  1898.  and  Flexner,  "Jour. 
Exper.  Med..'"  vol.  iii.  1898.  More  recent  papers  may  be  traced  from  the  articles 
by  Sanfelice.  "Centralbl.  f.  Bakt.,"  Bd.  xxxviii,  Jan.  2^5,  1905,  p.  30;  Citron,  "Zeit 
f.  .Hyg.  u.  Infektkrank.,"  1905.  Bd.  49:  Vincenzi,"  Gazette  degli  Osped.  e  delle 
Clin.."  1904:    Koehler  and  Hall.  "Jour,  of  Cutaneous  Dis.."  Dec.  1904. 


HACTKkIA   AS  CAUSES  OF   DISKASIJ. 


tain  animal  parasites  (\v<jrnis  aiul  ova)  ina\'  prodiuc  pulmonary  lesions 
not  unlike  those  of  tuberculosis.  Of  the  vejL^etuhle  parasites  endowed 
with  this  ([uality  special  mention  should  be  made  of  the  organisms 
isolated  from  butter  and  nnlk  by  Rabinowitseh.  Horn.  Moller.  and 
others,  and  the  organisms  ft)und  in  grass  by  Moller,  in  sewage  by  Hous 
ton,  in  earth  1)V  Karlinski,  and  in  manure  by  Moller,  and  others.  A 
number  of  these  organisms  injected  into  the  lower  animals  give  rise 
to  nodules  possessing  the  histology  of  similar  structures  produced  by 
the  tubercle  bacillus.  The  lesions  resulting  from  infection  by  some 
of  the  saccharomvces  may  also  resemble  tuberculosis.  I'vXactly  how 
common  these  ])rocesses  are  in  man  is  not  known,  but  it  is  highly  prob- 
able that  manv  cases  of  atypical  or  irregular  tuberculosis,  if  carefully 
studied,  would  be  found  to  be  instances  of  pseudotuberculosis  and 
could  ]irobablv  be  traced  to  a  yeast,  mould,  or  bacterium  other  than 
the  tubercle  bacillus. 

Leprosy'  is  an  extremely  refractory,  chronic  infectious  disease 
commuiiKablc  under  certain  conditions  and  due  to  the  Bacillus  leprae 
(Hansen).  The  organism  resembles  the  bacillus  of  tuberculosis  both  in 
mor])hologv  and  stain  reaction.  It  is  non-motile  and  measures  4  ,"  to  6  ," 
in  length  and  o.b  ,".  in  thickness.  Rost  believes  that  he  has  succeeded 
in  cultivating  the  organism  on  sodium-chlorid-free  media.  From  fluid 
cultures  of  the  organism  he  has  produced  a  leprolin,  which,  when  in- 
jected into  patients  affected  with  the  disease,  gives  rise  to  a  reaction 
resembling  that  produced  l)y  tuberculin  in  cases  of  tuberculosis,  although 
of  somewhat  longer  duration.  Leprolin  is  made  and  used  in  essentially 
the  same  wav  as  tuberculin.  Rost  reports  cases  of  leprosy  cured  by 
the  administration  of  the  fluid  i^repared  by  his  method.  According 
to  the  report  of  Rudolf.  16  ]jatients  have  been  discharged  cured.  So 
far  as  I  am  aware.  Rost's  observations  have  been  neither  disproved 
nor  verified. 

Dcntoitstration. — The  bacillus  of  leprosy  can  be  colored  by  the  same 
methods  used  for  demonstrating  the  tubercle  bacillus  and  also  by  ordi- 
narv  aqueous  solutions  of  anilin  dyes.  The  organism  is  Gram-positive. 
For  demonstrating  the  presence  of  the  bacillus  in  tissues  small  fragments 
are  macerated  in  a  glass  mortar  with  a  few  droj)s  of  normal  salt  solution 
and  the  resulting  tissue  emulsion  spread  on  cover-glasses,  dried,  fixed, 
and  stained  as  directed  for  tul)ercle  bacilli.  When  excised  tissues 
can  not  be  obtained  the  leprous  nodule  may  be  s(iueezed  between  the 
blades  of  a  forceps,  punctured  with  a  large  needle  or  a  small  knife, 
and  the  expressed  juice  s])read  on  covers  and  stained.  The  bacilli  are 
often  found  in  clumps  or  irregular  masses,  or  within  the  so-called 
lepra  cells,  especially  in  properly  fixed  and   stained   sections  i)repare<i 

'  See  works  referred  to  in  foot-note.  \>.  Si.      Nicolle.  "Aead.  '[^'^  ^},-''}''-\^'=> 
and  27.  iQo;;.   'La  Presse  Med."  .March  i.  1905,  p.  1^4.   "La  Soin.  Med..     March  N. 
100s   p.  I  16'    McDonald.   '  jour  .\mer.  Med.  A-ssoc."  June  6.  i()0,%.y.  1567.    Ihomi- 
son'  ■■  Report  of  the  Board"  of  Health  on  Lepmsv  in  New  South  W  ales  for  the  Vear 
iQov''      Rost.   •Indian   .Med    Cazette."   May.  Jun^--  *'"^1    ^^^''■-   ">°-».  «'»"     'B"! 
Med.   lour..-  Feb.   ii.  iqov      Ru.l-.lf.    'MedKine."  March,  "ios.  P.  i75-       \?^*^"' 
•Brit^    Med.    lour."  Sept."  17.   i0O4.     Orinshy.     Jour.  Amcr.  Med.  Assoc         Dee 
,1.  1Q04.     Sukurane.  ■'Centralhl.  f.  allj,'.   Path.  u.  path.  Anat..     100.?     Bd.    xiv. 
p.    no.      leanselme.    "La     Presse     M^-d."    Sept.    21.    1904.    P-    601.      Dorendorf. 
•Annalcs  of  Otol     Larvnjjol..  and  Rhinol.."  June.  1904-      In  addition  to  the  lort- 
jioing.  good  studies  of' leprosy  will  be  found  in   the  records  of  the  vanous   con- 
gresses devoted  to  the  subject. 


158 


GENERAL    PATHOLOGY. 


from  excised  tissues.  Beaded  and  granular  forms  are  usually  present. 
The  organisms  are  rarely  found  in  the  circulating  blood,  although  post- 
mortem they  may  be  demonstrated  in  the  organs. 

Pathogenesis. — Leprosy  as  a  disease  is  restricted  to  man.  By  in- 
oculation, Nicolle  has  succeeded  in  producing  a  typical  leprous  nodule 
in  the  Macacus  simensis.  The  tissues  removed  from  two  inoculated 
animals  contained  bacilli  identical  with  those  found  in  the  original 
lesion,  and  the  structure  of  the  nodule  produced  was  essentially  similar 
to  that  of  the  nodules  found  in  man.  With  regard  to  the  propagation 
of  the  disease  we  are  indifferently  enlightened.  It  is  feebly  contagious 
and  in  susceptible  individuals  easily  inoculated.  Jonathan  Hutchin- 
son's belief  in  a  fish  diet  as  a  predisposing  factor — if  not  actually  the 
cause — ^has  not  been  received  with  general  approbation.  The  period  of 
incubation  is  in  some  cases  longer  than  that  of  any  other  disease  of 
which  we  have  accurate  knowledge.  Cases  of  leprosy  have  been  re- 
ported in  which  the  first  symptoms  appeared  two  or  three  decades  after 

exposure  to  infection.  Leprosy 
occurs  in  two  chief  clinical  forms, 
although  be  th  of  these  may  be  pres- 
ent in  a  single  case. 

Anesthetic,  smooth,  or  trophoneu- 
rotic leprosy  involves  the  nerves, 
skin,  bones,  and  viscera.  The  nerves 
most  commonly  affected  are  the 
ulnar,  median,  radial,  musculospiral, 
intercostohumeral,  external  cuta- 
neous, posterior  tibial,  and  peroneal. 
The  nerve  affected  is  red,  swollen, 
and  rounded  in  shape;  later  it  be- 
comes harder,  pale  and  grayish  in 
color,  with  nodular  or  fusiform 
enlargements.  Microscopically,  the 
neurilemma  may  or  may  not  be 
changed;  in  most  cases,  however,  it 
becomes  thickened,  fibrous,  and  in- 
filtrated with  granule  cells  (lepra  cells  and  lymphoid  cells).  Cicatrization 
and  contraction  may  arrest  function  and  eventually  destroy  the  diseased 
nerve.  The  nerve  lesion  of  leprosy  begins  as  a  perineuritis;  the  later  de- 
generative changes  are  apparently  due  to  the  pressure  upon  the  nerve  and 
to  interference  with  nutrition.  Occasionally,  the  central  nervous  system 
shows  some  edema,  and  there  may  be  an  excess  of  fluid  in  the  ventricles 
and  in  the  subarachnoid  space.  The  larger  nerve-trunks  are  likely  to  show 
some  fibroid  hyperplasia,  with  slight  atrophy;  the  cutaneous  nerves  are 
degenerated,  hence  the  skin  is  anesthetic;  the  hair-bulbs,  the  sweat- 
glands,  and  the  sebaceous  glands  are  atrophied  and  fibroid.  The 
eruptions  of  leprosy  assume  a  number  of  forms.  They  are  sometimes 
erythematous;  frequently  attended  by  pigmentation,  and  at  other 
times  by  reduction  in  the  normal  pigment.  In  purely  anesthetic  leprosy 
the  maculae  are  never  elevated  until  late  in  the  disease.  As  the  result 
of  the  trophoneurotic  disturbance,  muscular  contractures  occur;  these 
may  be  followed  by,  or  associated  with,  a  varying  quantity  of  muscle 
atrophy.     The  fact  that  the  patient  feels  no  pain  as  a  result  of  injury 


Fig.  85. — Bacillus  lepre  (Extracellular). 


BACTKKIA   AS  CAUSES  OF   DISEASK.  151; 

of  the  affected  i)art  teiuls  to  imrcasc  the  danger  Ironi  this  source.  I 
have  seen  a  case  ot  lc])rosy  in  wliich  the  ])aticnt,  a  pipe-smoker,  had 
burne<l  oft'  the  ends  of  liis  fingers  by  i)ressing  the  tobacco  down  into  his 
pipe.      Necrosis  and  rarics  of  the  long  bones  have  been  observed. 

Tubercular  or  Nodular  Leprosy.— Witli  infection  of  the  skin  or  mucous 
membranes,  preceded  l)y  the  so-called  prodromal  eruptions,  typical 
leprous  tubercles  are  developed;  "they  may  be  flat  or  prominent,  oblong 
or  round,  isolated  or  confluent,  and  in  color  varying  from  pale  violet 
to  dark  l)rown;  ....  they  are  generally  soft,  but  may  be  hard" 
(Danielssen  and  Boeck).  These  tubercles  occur  anywhere  on  the  body, 
with  the  exception  of  the  scalp;  they  are  also  rare  in  the  palms  of  the 
hands  and  on  the  soles  of  the  feet.  Microscopically,  each  tubercle  is 
made  up  of  granulomatous  tissue,  composed  of  lymphoid  and  epithelioid 
cells  retained  in  a  loose  connective-tissue  matrix;  in  these  masses 
the  bacilli  abound,  both  between  and  in  the  cells.  Liquefaction  necrosis 
occurs,  followed  by  infection  with  pyogenic  organisms,  terminating  in 
ulceration;  such  ulcers  often  heal  rapidly;  others,  by  extension,  may 
give  rise  to  large  sloughing  areas ;  the  nodules  occur  also  on  the  mucous 
membranes,  particularly  those  of  the  nose  and  larynx.  The  bacilli 
mav  invade  the  viscera— lung,  liver,  spleen,  and  kid- 
nevs— in  which  thev  occasionally  give   rise  to   leprous  /> 

nodulo.  v/|V\ 

Mixed  forms  of   leprosy  are  not  uncommonly  seen,  ^''^''1' 

both  the  anesthetic  and  the  tubercular  types  being  pres-  (V^ 

ent.     In  other  cases  an  attack  of  the  anesthetic  form  N^S^^ 

terminates  in  the  tubercular,  or  a  patient  having  the  '^ 

tubercular  type  develops  evidences  of  extensive  anes-     vir..^  "'^Rrs^^rH^. 
thesia.     It  is  held  by  many  observers  that  the  so-called  oMA'"''°o'r<^* 

mixed  form  is  not  truly  a  variety  of  leprosy,  but.  is  the  .liamctert. 

ideal,  complete,  fully  develo])ed  disease,  and  that  the 
anesthetic  and  nodular  types  are  incompletely  evolved  forms.  Lepra 
mutilans  and  the  so-called  ganiircnoiis  leprosy  are  inappropriate  names 
intended  to  describe  the  conditions  rather  than  the  disease.  Leprosy 
mav  be  complicated  by  the  occurrence  of  other  processes ;  tuberculosis 
is  frequent,  and  inflammations  of  the  kidney,  septicemia,  pyemia, 
extensive  intestinal  ulceration,  amyloid  disease,  etc..  are  frequent  as- 
sociated  lesions. 

Rhinoscleroma '  is  an  affection  characterized  by  thickening  an.l 
induration  of  the  nasal  submucosa,  but  occasionally  mvolving  the 
pharvnx  or  larvnx.  The  tumefaction  usually  begins  in  the  nose;  the 
affected  areas  are  at  first  red  or  pink  and  very  tender,  later  they  become 
white.  In  these  masses  of  granulation  tissue  numerous  large  round  or 
oval  cells  (Mikulicz  cell)  containing  many  bacilli  are  constantly  present, 
and  the  same  organisms  are  found  free  in  the  lym])h-spaces  of  the  tissue. 
The  rod-shaped,  encapsulated  germ  (Bacillus  rhinoscleromatis)  closely 
resembles  the  bacillus  of  Friedlander.  some  believing  that  the  two 
organisms  are  identical.  It  is  stated  that  cultures  of  the  bacillus  of 
rhinoscleroma  are  a  little  more  transparent,  the  nail-head  surface  growth 
slightlv  more  grav.  and  the  capsules  persist  longer  in  cultures  on  solid 
media'     The  r)acillus  is  not  completely  decolorized  by  Gram's  method 

'  See  works  referred  to  in  fo..t.n,,t.v  p.  3i. 


i6o 


GENERAL    PATHOLOGY. 


Glanders'  is  an  infectious  disease  due  to  the  Bacillus  mallei,  a  rod- 
shaped,  motile/  facultative  anaerobic  organism  measuring  2  //.  to  5  //.  in 
length  and  0.5  ,".  to  i  //  in  breadth;  ovoidal,  pyriform,  and  swollen  ele- 
ments are  found  in  most  cultures,  and  sometimes  long  filaments  are 
formed.  Marx  has  described  branching  types,  resembling  the  clado- 
thrix  or  streptothrix.  Some  of  the  bacilli  contain  stained  and  unstained 
areas.  The  optimum  temperature  is  37°  C,  the  minimum  25°  C,  maxi- 
mum 42°  C,  and  the  thermal  death-point  between  55°  C.  and  60°  C. 
It  is  not  probable  that  the  Bacillus  mallei  forms  spores,  although  upon 
this  point  there  is  some  doubt. 

The  glanders  bacillus  grows  well  on  all  the  ordinary  media,  but 
glycerin-agar  is  especially  adapted  to  the  organism.  The  surface  growth 
consists  of  a  pale,  white,  moist,  transparent,  and  slimy  film,  following 
the  track  of  the  inoculating  needle;  transverse  striations  are  sometimes 
present.  In  bouillon,  it  produces  turbidity  followed  by  sedimentation. 
Potato  cultures  are  the  most  characteristic ;  by  the  second  dav  the  bacillus 

gives  rise  to  a  thin,  slightly  yellow- 
ish, transparent  layer,  which  in  the 
course  of  a  week  takes  a  reddish- 
brown  (chocolate  or  "cafe-au-lait") 
color  with  yellow  or  greenish-yel- 
low tinging  of  the  medium  at  the 
margin  of  the  growth. 

Dcnioustration. — The  Bacillus 
mallei  recjuires  prolonged  staining 
with  the  usual  anilin  dyes,  is  easilv 
decolorized,  and  Gram-negative. 
For  diagnostic  purposes  the 
method  of  Strauss  is  commonlv 
employed.  A  small  fragment  of 
infected  tissue  or  a  minute  quantitv 
of  the  culture  thoroughly  macer- 
ated in  sterile  water  is  injected 
into  the  peritoneal  cavitv  of  a 
male  guinea  -  pig.  Frothingham 
recommends  that  an  ordinary  swab,  such  as  is  used  for  diphtheria  diag- 
nosis (see  page  118),  be  rubbed  over  the  infected  area  and  expressed  in 
3  c.c.  of  sterile  water  which  is  used  for  the  injection.  As  the  animal  mav 
die  from  associated  pyogenic  infection,  more  than  one  guinea-pig,  prefer- 
ably a  number,  should  be  injected.  Within  twenty-four  to  fortv-eight 
hours  foci  of  suppuration  attack  the  peritoneal  lining  of  the  scrotal  sac, 
forming  adhesions  to  the  testicle,  which,  later,  also  becomes  involved. 
Usually  both  sides  are  aflfected,  but  to  difTerent  degrees.  Abscesses  mav 
develop   along  the   needle  track,  and   later  inflammation  of  the  nasal 

■See  references  given  in  foot-note  on  p.  Si.  Frothingham,  "Jour.  Med.  Re- 
search," Nov.,  1901.  Coleman  and  Ewing.  "Jour.  Meu-  Research,'"'  Mav,  1903,  p. 
223.  Gutowski,  "Arch.  gen.  de  Med.,"  Sept.  i,  1903.  Kleine,  "Zeit.'f.  Hv;?.  u. 
Infectkrank.,"  1903,  Bd.  44,  H.  2.  Heanley,  "Lancet,"  Feb.  6,  1904,  p.  364. 
MacCallum,  "Beitr.  zur  path.  Anat.."  1902,  Bd.  xxxi,  p.  440.  Wherrv,  Bulletin 
No.  24,  November,  1904,  Biological  Laboratories,  Dept.  of  the  Interior.  Bureau 
of  Government  Laboratories. 

'  Motility  is  not  a  constant  phenomenon,  and  some  observers  (Muir  and 
Ritchie)  denv  its  existence. 


Fig.  87. — Bacillus  mallei,  Pure  Culture. 


BACTKRIA   AS   CAUSES  OK   DISKASK.  1  f)  J 

mucosa,  joint  swelling,  ami  tharacteristic  nodules  may  be  found  in  the 
viscera.  Gutowski  rccommemls  a  modilication  of  Mari's  method,  which 
consists  in  inoculating  kittens  which  are  killed  at  the  expiration  of 
forty-light  hours  and  cultures  made  upon  agar  from  the  spleen  and  Idood. 

Mallein  is  prepared  in  the  same  manner  as  tuberculin  (see  page  147) 
and  for  diagnostic  purposes  is  used  in  the  same  manner.  The  maximum 
temperature  rise  is  determined  in  from  eight  to  eighteen  hours,  and 
should,  for  a  positive  diagnosis,  exceed  1.5°  C.  A  positive  reaction  is 
also  manifested  by  more  or  less  prostration  and  marked  local  swelling 
(12  cm.  to  15  cm.  in  diameter),  which  does  not  subside  for  a  week  or 
more.  Heanley  does  not  think  that  confidence  should  be  i)laced  in  the 
agglutination  test,  although  animals  may  yield  sera  containing  agglu- 
tinins for  the  bacillus. 

Patliogotcsis. — The  Bacillus  mallei  is  pathogenic  for  horses,  asses, 
mules,  sheep,  goats,  dogs,  cats,  lions,  tigers,  field-mice,  and  ground 
squirrels;  cattle,  white  mice,  rats,  and  birds  are  immune.  The  rabbit 
is  refractory  but  susceptible. 

Glanders  in  man  occurs  in  two  forms:  (i)  Localized,  circumscribed, 
or  chronic  glanders,  or  farcy;  (2)  general,  disseminated,  acute,  or  septi- 
cemic glanders. 

Localized  Glanders. — Infection  by  the  Bacillus  mallei,  involving 
the  skin  and  adjacent  lymph-glands,  is  called  farcy;  when  the  mucous 
membranes  are  affected,  the  condition  is  spoken  of  as  glanders.  At 
one  time  it  was  customary  to  describe  acute  and  chronic  glanders  and 
acute  and  chronic  farcy,  but  it  is  now  recognized  that  glanders  and 
farcy  are  due  to  the  same  cause,  and  that  there  is  no  essential  difference 
between  the  pathology  of  the  "farcy  bud"  and  the  glanders  nodule. 
Bv  some  the  local  or  chronic  manifestation  of  infection  with  the  bacillus 
mallei  is  called  glanders,  while  the  term  farcy  is  applied  to  the  general, 
disseminated,  acute,  or  septicemic  glanders. 

It  does  not  seem  probable  that  the  organism  can  gain  ingress  except 
through  an  abraded  or  wounded  surface,  although  experiments  are 
not  wanting  to  show  that  the  bacillus  may  be  forced  into  the  skin  when 
applied  by  inunction  with  even  slight  friction.  As  communicated 
to  man,  the  disease  usually  is  contracted  from  the  horse,  and  is  there- 
fore most  common  in  hostlers  and  those  employed  around  stables,  etc. 
When  the  glanders  bacilli  localize  in  the  su1)cutaneous  or  submucous 
tissue,  there  develops  a  small  nodule,  rarely  as  large  as  a  pea,  made  up 
of  an  almost  pure  leukocytic  infiltrate,  containing  a  few  giant-cells  and 
the  characteristic  l)acilli.  By  necrosis,  the  nodule  and  adjacent  mucous 
membrane  or  skin  soften  and  disintegrate;  the  resulting  ulcer  is  usually 
foul,  without  any  abundant  discharge;  when  a  number  of  ulcers  are 
located  near  one  another,  they  not  uncommonly  show  a  decided  dis- 
position to  become  confluent,  forming  irregxdar  serpiginous  ulcers. 
There  is  likelv  to  be  lymi)hangitis  extending  to  the  neighboring  lymph- 
nodes,  which  may  become  large  and  suppurate.  This  constitutes  the 
so-called  chronic  glanders  or  chronic  farcy.  Chronic  glanders  not 
infrequentlv  runs  an  extremely  ])rotraited  cour.se:  von  Baracz  reported 
a  ca.se  in  which  the  disease  lasted  fifteen  years,  during  which  time  it  was 
wholly  latent  for  an  interval  of  five  years. 

Acute  Glanders. — In  the  acute  form  the  condition  more  closely 
resembles  miliarv  tuberculosis  in  the  rapid  dis^emin.ition  nf  the  noi.son 


l62  GENERAL  PATHOLOGY. 

and  the  wide-spread  distribution  of  the  lesions.  Weichselbaum  describes 
a  case  of  acute  glanders  in  which,  without  any  apparent  initial  lesion, 
there  occurred,  throughout  the  viscera,  multiple  nodules,  the  character  of 
which  was  not  diagnosticated  during  life ;  at  the  postmortem  a  thrombus 
was  found  in  one  of  the  meningeal  veins,  and  from  this,  no  doubt,  had 
arisen  infected  emboli,  which  had  given  rise  to  the  general  dissemination 
of  the  lesion.  In  this  condition  the  bacilli  are  found  in  the  blood 
and  in  the  discharges ;  multiple  cutaneous  eruptions  are  likely  to  occur ; 
the  larger  joints  may  be  implicated,  as  in  other  forms  of  septicemia;  in 
the  male  the  testicles  may  be  involved.  Multiple  abscesses  may  occur 
throughout  the  body,  closely  resembling  pyemia.  Death  usually  occurs 
from  exhaustion.  This  constitutes  the  septicemic  form  of  the  disease, 
and  may  occur  (i)  without  any  initial  lesion  that  can  be  discerned; 

(2)  it  may  be  associated  with  an  initial  lesion  that  runs  a  rapid  course; 

(3)  it  may  terminate  the  chronic  form  of  farcy  or  glanders,  as  already 
described. 

The  secondary  changes  that  may  occur  in  a  farcy  nodule  resemble  in 
some  respects  those  seen  in  tubercles.  Latent  or  "healed-in"  nodules 
are  not  infrequent;  they  commonly  show  peripheral  fibrosis  and  cal- 
careous infiltration  similar  to  that  already  described  when  considering 
"healed-in"  tubercles.  (See  p.  151.)  Such  latent  masses  are  seen  in 
lymph-nodes  and  in  the  lung,  and  occasionally  in  other  viscera.  During 
the  development  of  the  farcy  node  interstitial  and  peripheral  hemor- 
rhages are  not  infrequent,  and  in  the  lung  an  associated  pneumonia  is 
usually  present.  The  latter  may  be  restricted  to  a  small  zone  around  the 
node  or  it  may,  as  in  tuberculosis,  involve  a  large  area  of  the  pulmon- 
ary tissue,  giving  rise  to  alterations  that  closely  resemble  those  of  croup- 
ous pneumonia .  The  routes  of  infection  and  dissemination  are  practically 
the  same  as  those  already  given  for  tuberculosis.  The  occurrence  of 
multiple  abscesses  scattered  throughout  the  body,  containing  staphylo- 
cocci as  well  as  the  specific  organism  of  the  disease,  is  indicative  of  the 
pyemic  character  of  the  lesion.  The  erythematous,  papular,  phlyctenu- 
lar, bullous,  and  pustular  eruptions,  are  also  evidences  of  general 
infection;  the}^  have  led  to  confusion  in  diagnosis,  the  disease  having 
been  mistaken  for  measles,  chicken-pox,  smallpox,  syphilis,  etc. 

HYPHOMYCETES. 

The  Hyphomycetes  or  mould  fungi  consist  of  a  branched,  septate, 
filamentary  meshwork  composed  of  mycelium,  from  which  arise  hyphae 
and  conidia  producing  small,  spheric,  highly  refractile  bodies  called 
spores.  The  special  organs  by  which  spores  are  produced  are  not  always 
the  same.  Members  of  the  higher  group  of  moulds  are  easily  identified, 
but  as  the  scale  is  descended  some  of  the  special  forms  are  not,  with 
our  present  knowledge,  readily  classified.  A  number  of  the  moulds  are 
pathogenic  for  lower  animals,  but  under  ordinary  conditions  a  few  only 
give  rise  to  disease  in  man. 

Aspergillosis^    is    a  morbid    process    induced    by   members   of    the 

*  Renon,  "Etude  sur  I'Aspergillose  chez  les  Animatix  et  chez  rhomme," 
Paris,  1897.  Bosin,  "Centralbl.  f.  Bact.,"  xxxii,  p.  589.  Pearson  and  Ravenel, 
"Univ.  of  Penna.  Med.  Magazine,"  August,  1900.  .  Ritter,  "Prag.  med.  Woch.," 
Feb.  2,  1902.  Cook,  "Amer.  Med.,"  Dec.  5,  1903.  Elliott,  "Ophthalmic  Record," 
Nov.,  1902,  p.  582.  Nakaj^ama,  "Zeit.  f.  Heilk.,"  1903,  Bd.  xxiv,  Abth.  f.  path. 
Anat.,  H.  4,  p.  548.      Birkett  and  NichoUs,  "Montreal  Med.  Jour.,"  May,  1904. 


BACTERIA   AS   CAUSES  OP  DISEASE.  I  63 

aspergillus  group.  Tlic  Aspergillus  fumigatus,  Aspergillus  flavus,  and 
Aspergillus  niger  are  the  most  important  (liseasc-i)rocluiing  species. 
They  occasionally  give  rise  to  inflammation  of  the  external  and  middle 
ear,  and  a  definite  form  of  aspcrgilltis  keratitis  has  heen  described.  A 
most  important  morbid  process  produced  by  the  parasite  is  pneumo- 
aspergillosis,  which  may  be  primary  or  secondary.  It  is  probable  that 
in  a  considerable  percentage  of  cases  the  fungus  is  engrafted  upon,  and 
extends  into,  some  previously  existing  pulmonary  lesion.  The  disease  is 
seen  particularly  in  millers  and  in  other  persons  handling  grain,  and  in 
pigeon-feeders  addicted  to  moistening  seeds  in  the  mouth.  The  Asper- 
gillus fumigatus  grows  at  a  higher  temperature  (35°  C.  to  40°  C.)  than  the 
niger  (25°  C),  which  may  account  for  the  fact  that  the  former  is  more 
commonly  pathogenic.  The  pulmonary  lesion  produced  by  the  fungus 
is  essentially  a  pseudotuberculosis  and  may  be  acute  or  chronic.  The 
bronchi  are  frequently  dilated,  cavities  form,  and  in  the  chronic  cases 
there  is  a  notable  interstitial  pneumonia.  Histologically  the  lesions 
consist  of  masses  of 
leukcoytes,  among 
which  the  mycelium 
of  the  fungus  is  widely 
distributed.  There 
is  usually  marked 
bronchial  thickening 
continuous  with  the 
increased  connective 
tissue  in  the  lung. 

It  is  not  known 
that  the  members  of 
this  group  produce  a 

toxin,  all  experiments                                               ___^ 
going    to    show  that                               ^"^^        ^9/^  ^y^ 
they  do   not;   it   has  ^ -^v- 

been    claimed,^     how-  tic.  SS.— Aspergillus. 

ever,   that   pellagra  is  .1.  Mycelium.    B.  opened  sionuigium.    C.  Free  spore. 

due  to  a  toxic    sub- 
stance produced  in  maize  by  mould  fungi,  among  which  the  aspergillus 
is  thought  to  be  active. 

The  dermatomy coses-  are  specific  fonns  of  cutaneous  inflammation 
due  to  other  members  of  the  mould  family.  The  most  important  of 
these  are  favus,  herpes  tonsurans  (tinea  tonsurans  or  barbers'  itch), 
tinea  versicolor  (pityriasis,  mycosis  versicolor,  or  demiatomycosis 
furfuracea),  and  ervthrasma. 

Favus  is  usually  restricted  to  the  scalp,  although  Moms  reported 
a  case  in  which  the  lesion  occurred  on  the  scalp,  trunk,  and  arms  and 
also  involved  the  finger-nails.  Sulphur  yellow  crusts  form  about  hairs 
which  the  mvcelia  and  conidia  penetrate;  the  undcriying  skin  inflames, 
the  hair  sheds,  and,  as  a  result  of  inflammatory  and  atrophic  changes 
in   the   bulbs,   may   not   be   reproduced.     The   parasite   producing   the 

'  Ceni  and  Besta,  "Rivista  sper.  di  Feniatria."  1904.  vol.  xxx.  P- 865. 

»Sabouraud,  *Les  Tricophvtics  Humaincs."  Pans.  1894.  Bodin  Lcs 
Champignons  Parasites  de  Ihommc."  1902.  Bunch.  "Lancet."  Feb.  18.  1905. 
Minne,  "An.  de  la  Soc.  de  Med.  de  Fland.,"  1904.  Ixxxin. 


164 


GENERAL  PATHOLOGY. 


lesion  is  the  Achorion  schbnleinii.     The  spores  of  the  thread  penetrate 
the  hair-foUicle  and  may  be  found  surrounding  the  bulb. 

The  organism  is  not  difficult  to  grow,  but  on  account  of  the  large 
number  of  associated  bacteria,  isolation  in  pure  culture  is  not  easy;  the 
extracted  hair  may  be  washed  in  sterile  water  and,  by  sterile  instruments, 
divided  into  many  fragments,  of  which  inoculations  may  be  made. 
Parts  of  the  bulb  are  most  likely  to  yield  pure  cultures.  On  agar  the 
outlines  are  clear,  the  surface  scaly,  and  in  old  growths  cerebriform: 
the  surface  takes  on  a  fine,  whitish,  powdery  appearance.  On  gelatin, 
irregular,  whitish,  downy  growths  develop  with  slowly  advancing  lique- 
faction of  the  medium.  The  organism  may  be  successfully  inoculated 
on  the  gray  mouse.  There  are  other  members  of  the  favus  group  that 
affect  the  lower  animals  and  occasionally  are  communicated  to  man. 

Herpes  or  tinea  tonsurans  is  a  form  of  ring^^orm  attacking  the  scalp 
and  due  to  the  trichophyton  tonsurans,  of  which  there  are  two  principal 
forms,  the  trichophyton  microsporon  and  the  trichophyton  megalosporon. 
The  small  spore  parasite,  called  by  Sabouraud  the  microsporon  Audouini, 

affects  children,  and  its  lesions 
are  practically  restricted  to  the 
scalp;  the  mycelia  penetrate  the 
hairs,  which  become  brittle  and 
readily  fragment.  Usually  there 
is  not  much  inflammation,  although 
the  thread  attaches  itself  to  the 
cuticle  of  the  hair-shaft.  The 
spores  vary  from  3  //  to  4  //.  and 
extend  into  the  hair  a  short  dis- 
tance above  the  bulb.  On  agar 
containing  one  per  cent,  peptone 
and  three  per  cent,  maltose  the 
organism  produces  a  central  eleva- 
tion, and  an  areola  of  powder- 
like  rays,  creamy-white  in  color. 
Tinea  versicolor  is  due  to  the 
microsporon  furfur,  a  parasite  the 
hyphse  and  myceHa  of  which  are  smaller  than  the  parasites  described 
above.  The  disease  affects  particularly  the  trunk  and  limbs,  giving 
rise  to  yellow,  yellowish,  or  dark-brown  spots  or  larger  areas;  the 
hands,  feet,  and  face  usually  escape.  If  small  fragments  of  the  des- 
quamating lesion  be  softened  in  liquor  potassae,  washed  in  alcohol  and 
ether,  and  mounted  in  glycerin,  mycelial  threads  3  //  to  4  //  in  diameter, 
curved  and  U-shaped  but  not  ramified,  mav  readily  be  recognized; 
round  and  double  contoured  spores  are  also  present.  "  Reports  of  suc- 
cessful cultivation  have  been  made,  but  remain  unverified. 

Erythrasma  is  due  to  the  Microsporon  minutissimum.  The  lesion  is 
seen  particularly  on  the  inner  aspect  of  the  thighs  and  is  manifested 
by  the  occurrence  of  brownish  patches  with  but  little  desquamation. 
The  parasite  can  be  demonstrated  in  the  desquamated  epithelial  cells  as 
short  mycelia  from  0.6  'j-  to  i  ,".  in  diameter  and  varving  in  length  from 
ovoids  to  threads  extending  beyond  the  cell  boundaries. 

For  the  demonstration  of  fungi  in  dermatomy coses  the  crusts,  epi- 
thelial scales,  or  hairs  may  be  shaken  with  ether,  the  excess  of  which 


Fig.  89. — Favus  from  a  Mouse. — {Coplin  and  Bevan.) 

X  800  diameters. 
a.  Germinating  tube  from  gelatin  culture.    &.  Conidia. 

c.    Formation    of    fruit.       d.    Mycelial    threads 

with  fructification. 


HACTKkIA   AS  CAUSES  OF   DISEASE.  165 

is  poured  off  and  the  specimen  covered  with  liquor  potassiE;  in  from  a 
few  hours  to  several  days,  dependinj^'  \ipon  the  size  of  the  specimen, 
the  tissue  softens,  dissociates,  and  can  be  crushed  and  examined  micro- 
scopicall)'.  After  dissociation  in  liquor  potass^e,  staining  is  usually  dif- 
ficult, although  alcoholic  solutions  of  eosin  or  safranin  may  he  made 
to  tinge  the  parasites.  For  staining  the  hyphomycetes  in  horny  tissues 
Kraus'  recommends  the  methyl-grcen-j)yronin  blood  stain  of  Papj)en- 
heim,  which  should  be  obtained  from  Grubler.  Stain  for  five  minutes, 
wash  and  examine  in  water;  sometimes  better  results  are  obtained 
by  the  method  recommended  for  staining  the  spirocha?ta  found  in 
syphilis  (see  page  175). 

Thrush,  muguet,  soor,  or  preferably  mycotic  stomatitis,  is  a  parasitic 
affection  attacking  the  various  mucous  membranes,  but  esj>ecially  that  of 
the  mouth ;  it  is  manifested  by  redness,  more  or  less  catarrhal  inflammation , 
and  the  development  of  whitish  spots  resembling  flakes  of  curdled  milk. 
The  causative  fungus  infiltrates  between  the  epithelial  cells,  sometimes 
extending  downward  into  the  connective  tissue.  Mace^  believes  that  the 
infiltration  of  the  epithelium  is  brought  about  by  change  in  the  action  of 


Fig.  go. — MiCROSPORON  furfur. — (Coplin  and  Bevan.)      X6oo  diameteri. 

the  saliva  depending  upon  antecedent  or  associated  infection  by  pus 
cocci,  colon  bacilli,  and  possibly  other  organisms.  This  explanation, 
if  correct,  accounts  for  the  well-known  fact  that  the  disease  is  much 
more  common  in  the  debilitated,  and  rarely,  if  ever,  attacks  a  previ- 
ouslv  healthy  individual.  The  infection  may  involve  the  esophagus, 
and  rarelv  other  parts  of  the  alimentary  canal.  Smith  and  Radkey' 
report  an  instance  in  which  the  vagina  was  affected  (vaginitis  or 
colpitis  mvcotica).  Dark  or  l)rownish  thrush  areas  may  result  from 
extravasated  blood  infiltrating  the  diseased  tissue.  Oliver*  reports  a 
series  of  cases  of  mouth  infection  with  a  fungus  resembling  the  oidium; 
some  of  the  patients  were  otherwise  in  good  health,  and  most  of  the 
cases  were  chronic.  Frisch  has  found  the  bladder  involved.  Hiibner'^ 
records  a  general  infection  by  the  thrush  fungus  and  states  that  Concetti 

'  "Centralbl.  f.  Bakt.,"  St-pt.  2x,  1904,  p.  153. 

'  "  L'Obstretique."   IQ04,  viii.  No.   6. 

'  "Medical  News,"  June  27,  190,^.  P-  i204- 

*  "California  State  Jour,  of  Medicine,"  August,  1904,  p.  240 

*  "Deut.  mcd.  "Woch.."  1903,  p.  281. 


l66  GENERAL  PATHOLOGY. 

has  shown  conclusively  that  the  organism  produces  an  energetic  toxin. 
Zenker  and  Ritter  have  reported  brain  abscesses  due  to  the  parasite, 
and  Schmorl  has  found  it  in  abscess  of  the  kidney  and  spleen. 

The  parasite  causing  thrush  has  been  variously  classified  by  different 
writers;  the  names  given  the  germ — oidium  albicans,  monilia  conidia, 
saccharomyces  albicans,  thrush  fungus,  soorpilz,  and  muguet — indicate 
the  varied  views  that  have  been  held  as  to  its  botanical  position ;  oidium 
albicans  is  generally  preferred.  By  some  authorities  the  parasite  is 
believed  to  be  intermediate  between  the  moulds  and  3^easts.  It  forms 
branched  mycelia  and  spheric  or  oval  conidia.  The  branched  hyphse 
consist  of  short  cylindric  cells,  which  vary  slightly  in  thickness.  On 
milk,  bread-paste,  potato,  and  other  culture-media  the  oidium  albicans 
rapidly  forms  a  milk-white  growth,  extending  as  thready,  almost  color- 
less projections  into  the  substratum.  It  stains  with  the  usual  anilin 
dyes  and  by  Gram's  method. 


Fig.  91.— Oidium  .'Albicans  (Thrush  Fungus).—  Fig.  92.— Actinomyces  (Ray  Fungus).  From  Bovine 

(Cophn  and  Bevan.)  AcnNOMYCOSis.— (Ca/>/»»    atid    Sevan.)     X    800 

diameters. 

Actinomycosis*  is  a  disease  affecting  man  and  a  number  of  the  lower 
animals,  and  may  be  due  to  any  one  of  several  closely  allied  fungi  upon 
the  classification  of  which  authorities  are  not  agreed.     The  prevailing 

/  See  works  referred  to  in  foot-note,  p.  81.  Feistmantel,  "Centralbl.  f.  Bact.," 
XXXI,  1902,  p.  433.  Lignieres  and  Spitz,  "Arch.  Parasitologie,"  vol.  vii,  1903.  Foul- 
erton,  "Path.  Soc.  of  London,"  Nov.  4,  1902.  Levy,  "Sixth  Annual  Report  of  the 
Michigan  Acad,  of  Sci.,"  pp.  169-172.  McDonald,  "Edinburgh  Med.-Chir. 
Soc.,"  Feb.  3,  1904.  Biagi,  "Sperimentale,"  Iviii,  4,  1904.  Neukirch,  "Zeitsch. 
f.  Hyg.  u.  Infectionskr.,"  xlviii,  3,  1904.  Lagrange,  "Gaz.  hebd.  des  scienc. 
nied_.  de  Bordeaux,"  Nov.  6,  1904.  Knox,  "Lancet,"  Oct.  29,  1904,  p.  1204. 
Bodin,  "Bull,  de  la  Soc.  scient.  et  med.  de  I'Ouest,"  xii,  1903.  Enriquez  and 
Sicard,  "Soc.  Med.  des  Hop.,"  Paris,  May  13,  1904.  Bumham,  "Johns  Hop- 
kins Hospital  Bull.,"  April,  1904,  p.  136.  Wright,  "Amer.  Jour,  of  the  Med. 
Sci.,"  July,  1904.  Poncet,  "Acad,  de  Med.,"  April,  1904.  Meier,  "Diss.  med. 
Munchen,"  1904.  Thevenot,  "Gaz.  des  Hop.,"  Nov.  27,  1904.  Graff,  "Zeit.  f  . 
Heilkunde,"  1904,  Heft  10.  Heinrichs,  "Arch.  f.  Laryng.  u.  Rhinol.,"  1904,  Bd. 
16,  p.  350.  Lowe,  "Diss.  med.  Greifswald,"  1904.  Sanfelice,  "Centralbl.  f. 
Bakt.,"  June  16,  1904,  p.  355.  Dopke,  "Miinch.  med.  Woch.,"  Dec.  22,  1903. 
Gilbert^  "Zeit.  f.  Hyg.,"  Sept.,  1904,  p.  3S3.  Langer,  "Zeit.  f.  Hyg.  u.  Infectk.." 
1904,  Bd.  47,  H.  3.  Di  Donna,  "Ann.  Ig.  sperim.,"  t.  xiv,  f.  3,  1904,  pp.  449- 
459-  Warthm  and  Olney,  "Amer.  Jour,  of  Med.  Sci.,"  1904,  vol.  cxviii  p  637 
MacCallum,  "Centralbl.  f.  Bakt.,"  Bd.  xxxi.  No.  12,  May  14,  1902.  Stokes, 
"Amer.  Jour,  of  Med.  Sci.,"  Nov.,  1903,  p.  861.  Howard,  "Jour.  Med.  Research,'"' 
May,  1903,  and  Jan.,  1904. 


BACTERIA   AS   CAUSES   OF   DISEASE.  167 

custom  is  to  regard  the  parasite  of  actinomycosis  as  a  strcptothrix;  the 
terms  nocardia  and  cladothrix  are  also  used.  MacCallum  argues  strongly 
in  favor  of  the  generic  name  actinomyces,  and,  as  I  strongly  concur  in 
his  views,  I  shall  adhere  to  the  nomenclature  followed  in  the  preceding 
edition  of  this  book.  Studies  of  the  last  few  years  appear  to  have 
established  that  there  are  a  number  of  closely  allied  organisms  belonging 
to  this  group  and  that  the  clinical  phenomena  ordinarily  called  actinomy- 
cosis may  be  due  to  any  one  of  several  closely  related  parasites;  Stokes 
gives  a  table  recording  a  number  of  the  difTerences  between  indivulual 
members  of  the  group.  All  of  the  actinomyces  are  branching  fungi, 
non-motile,  spore-forming.  Gram-positive,  and  give  rise  to  dense,  ad- 
herent, often  shaggy  colonies  that  at  first  are  white  or  light  yello\y  in 
color,  but  in  older  gro\vi;hs  may  be  dark,  almost  brown.  The  actino- 
myces bovis  liquefies  gelatin;  none  of  the  organisms  produce  fermenta- 
tion; members  of  the  group  occurring  in  man  are  acid-fast,  showing  a 
stain  reaction  similar  to  that  of  the  tubercle  bacillus.  The  actinomyces 
in  culture  are  both  anaerobic  and 
aerobic,  although  some  forms  can 
not  be  grown  in  the  absence  of 
oxvgen;  attempts  to  make  this 
property  a  basis  of  classification 
have  been  unproductive.  The  germ 
is  extremely  pleomorphous.  giving 
rise  to  structures  so  dissimilar  that 
it  often  seems  difficult  to  believe 
that  the  culture  is  not  contamin- 
ated by  bacteria.  Of  the  various 
forms  assumed  by  the  parasite  the 
following  merit  special  considera- 
tion: The  branching  filaments 
rarelv  exceed  0.5  /'-  in  diameter  and 
in  young  cultures  are  uniform;  in 
older  growths  they  may  break  up 
into  rods  or  coccoid  bodies;  the 
filaments,  bacillus-like  and  coccoid 
bodies,  usually  possess  a  demon- 
strable outer  layer  or  sheath.     In 

cultures  the  mvcelia  extending  upward  develop  spores  or  gonidia.  Toward 
the  peripherv  of  the  masses  (actinomyces  granules)  in  the  tissues, 
pvriform.  club-like  bodies  possessing  great  diagnostic  significance  are 
u'suall V  found .  Such  bodies  develop  particularly  in  the  yellowish  granules 
frequentlv  present  in  actinomycotic  tissues  and  in  the  pus;  club-con- 
taining niasses  resemble  grains'of  iodoform,  or— as  a  result  of  calcareous 
deposit — grains  of  sand. 

Demonstration. — It  is  well  to  remember  that  in  demonstrated  acti- 
nomycotic lesions  the  fungus  is  often  absent  or  can  not  be  detected  during 
long' periods.  It  is  most  readily  found  in  the  discharges  from  freshly 
opened  lesions,  and  becomes  more  difficult  to  recognize  in  the  presence 
of  active  concurrent  infection,  particularly  when  the  latter  is  due  to 
other  pvogenic  organisms.  In  order  to  demonstrate  the  fungus  in  sus- 
pected material  (usually  pus),  spread  the  matter  on  a  sterile  gla.<;s  plate 
and  search  carefullv   for  yellow  or  yellowish-white  grains  that  closely 


Fig.  9j.— Actinomyces,  fbom  CiLniir 
The  spedmen  shows  branching  threads  .in.i  a  few 
slightly  dubbed  Ulomenu. 


l68  GENERAL  PATHOLOGY. 

resemble  granules  of  iodoform.  The  largest  of  these  tufts  will  appear 
about  the  size  of  a  pinhead.  With  a  needle  pick  out  one  of  these  grains, 
transfer  it  to  a  microscope  slide,  and  gently  cover;  examined  with  a  ^- 
inch  or  |-inch  objective,  these  grains  appear  spheroid  or  globular,  greenish 
in  color,  and  quite  opaque.  While  still  in  focus,  with  a  needle  make 
pressure  on  the  cover-glass,  focusing  slowly  downward;  when  the  granule 
falls  to  pieces,  as  it  soon  will,  under  a  higher  power  ({r-inch  dry  lens  or 
Y^2-iiich  oil  immersion),  the  club-shaped  masses  become  clearly  defined. 
Staining  is  not  necessary,  but  in  sections  or  cover-glass  spreads  beautiful 
results  may  be  obtained  by  the  following:  (i)  Carbolfuchsin,  ten 
minutes,  gently  warming  the  solution;  (2)  rinse  in  water;  (3)  saturated 
alcoholic  solution  of  picric  acid,  five  to  ten  minutes;  (4)  water,  five  to 
ten  minutes;  (5)  fifty  per  cent,  alcohol,  fifteen  minutes;  (6)  dehydrate 
in  absolute  alcohol;  (7)  clear  in  clove  oil;  (8)  mount  in  balsam  (Crook- 
shank-Plaut).  Sections  may  also  be  stained  in  carbolfuchsin,  largely 
decolorized  in  fifty  per  cent,  alcohol,  washed  in  water,  and  followed  by 
hematoxylin  in  the  usual  manner.  From  cultures,  the  fungus  stains 
with  most  of  the  anilin  dyes  and  by  Gram's  method. 

Pure  cultures  are  obtained  by  plating;  the  grains,  after  washing  in 
sterile  water,  are  crushed  in  the  nutrient  gelatin,  and  this  is  spread  as 
usual.  In  order  to  break  up  the  grains  and  to  diffuse  them  in  such  a 
way  as  to  secure  pure  cultures,  it  ;s  recommended  that  they  be  rubbed 
up  with  sterile  sand  and  plated  in  the  usual  manner.  In  from  four  to 
seven  days  the  colonies  appear,  and  are  then  inoculated  on  agar  or 
gelatin. 

The  path  of  infection  in  actinomycosis  may  be  through  almost 
any  surface  or  cavity  communicating  with  the  exterior.  The  frequency 
with  w^hich  the  disease  affects  the  head  and  neck  speaks  strongly  for 
oral  infection,  probably  through  some  abrasion  of  the  mucous  membrane 
or  possibly  a  diseased  tooth.  According  to  Wright,  there  are  six  cases 
of  established  tonsillar  infection.  This  observer  found  that  in  117 
cases  of  actinomycosis  the  jaws,  mouth,  or  pharynx  were  involved  in 
72.  Chiari  first  described  a  case  of  primary  infection,  probably  by 
mural  implantation,  of  the  intestinal  wall.  Burnham  has  been  able  to 
collect  32  cases  of  primary  actinomycotic  appendicitis. 

Morbid  Anatomy. — Once  the  fungus  secures  admission  to  the  con- 
nective tissues,  there  is  engendered  a  granulation  tumor  containing  large 
masses  of  lymphoid  cells,  a  few  epithelioid  elements,  and  giant-cells, 
very  closely  resembling  a  tubercle ;  the  lessened  tendency  to  necrosis 
or  caseation,  however,  permits  these  masses  to  accumulate  and  to 
become  of  considerable  size,  when,  prior  to  the  discovery  of  the  cause, 
thev  "were  not  uncommonly  mistaken  for  sarcomata.  The  size  of  the 
actinomvcotic  masses  varies.  The  larger  nodules,  which  ma}"  attain 
the  dimensions  of  a  fetal  head,  are  not  uncommonly  honeycombed, 
resembling  a  trabecular  structure,  the  stroma  of  which  is  formed  from 
the  connective  tissue  of  the  affected  part.  The  irregular  alveoli,  produced 
by  the  connective  tissue,  are  distended  by  inflammatory  products  con- 
taining the  parasite.  When  occurring  in  bone  or  on  the  skin,  the  resem- 
blance to  sarcoma  may  be  striking.  The  contents  of  actinomycotic 
masses  may,  as  a  result  of  the  pyogenic  powers  of  the  germ,  be  composed 
of  pus.  At  other  times  the  necrosing  and  pus-producing  properties  of 
the  parasite  are  absent,  and  in  some  of  these  cases  a  hyaline  fibrous 


BACTERIA   AS  CAUSES  OT   DISEASE.  I  69 

tissue  is  produced,  rendering  the  affected  structure  denser  than  normal 
{wooJoi  tongue);  this  type  corresponds  to  the  chronic  productive  or 
hyperplastic  form  of  tuberculosis  mentioned  on  page  153.  Like  tuber- 
culosis, actinomycotic  areas  may  calcify  or  encapsulate,  or  both  these 
changes  may  be  present.  Ulcers  formed  on  the  skin  are  crater-like,  and 
discharge  a  clear,  mucilaginous  fluid,  sometimes  in  large  ciuantities.  The 
local  extension  of  the  process  is  peculiar,  in  that  it  advances  steadily, 
involving  contiguous  tissues,  and  does  not  appear  to  follow  the  y^ath 
of  least  resistance,  such  as  the  course  of  a  muscle,  blood-vessel,  or  nerve, 
or  the  lymph-stream.  Penetration  of  venous  walls  permits  the 
formation  of  actinomycotic  thrombi,  which,  becoming  fragmented,  give 
rise  to  emboli  containing  the  specific  organism.  In  Ponfick's  case  such 
a  thrombus  occurred  in  the  jugular  vein,  and  later  embolic  metas- 
tasis showed  itself  in  the  heart,  lungs,  spleen,  and  brain.  Probably  on 
account  of  the  large  size  of  the  germ,  dissemination  by  the  lymph -stream 
is  less  common  than  by  the  blood-supply. 

In  over  fifty  per  cent,  of  the  cases  in  man  the  lesion  is  located  in  the 
tissues  of  the  head  and  neck.  The  intra-abdominal  organs  arc  next  in 
point  of  frequency,  the  lungs,  tongue,  and  skin  following  in  the  order 
given.  Actinomycosis  has  been  observed  in  the  generative  organs, 
particularly  in  the  Fallopian  tube;  the  reported  cases  of  actinomycosis 
of  the  female  reproductive  organs  are  of  special  interest,  particularly 
when  we  take  into  consideration  the  fact  that  only  about  one-third  of 
all  the  cases  of  actinomycosis  occur  in  women.  Actinomycosis  is  also 
seen  in  the  medulla  of  long  bones  and  in  the  cancellous  tissue  of  small 
bones,  and  has  been  described  in  the  mastoid  cells  and  middle  ear. 
Primary  pulmonary  actinomycosis  is  not  a  rare  form  of  the  affection ; 
primary  cerebral  actinomycosis  occurs,  although  brain  involvement  is 
usually  due  to  metastasis,  the  fungus  reaching  the  brain  from  a  jiriman.- 
lesion  elsewhere.  The  frequency  and  mortality  in  different  forms  of 
actinomycosis  are  shown  by  the  following  statistics  by  Poncet  and 
Th^venot.'  Of  the  306  cervico-facial  cases.  10  are  dead,  3  improved, 
168  cured,  while  in  125  the  result  is  not  known.  Among  25  infections 
of  the  thoracic  or  abdominal  wall,  4  are  dead.  16  cured,  and  in  5  the 
result  is  unknown.  The  viscera  of  the  abdomen  were  involved  in  84 
cases,  16  of  which  are  believed  to  have  been  cured,  17  are  dead,  and  51 
could  not  be  traced.  Of  71  pleuro-pulmonary  cases,  4  are  cured,  25 
dead  and  in  42  the  subsequent  history  could  not  be  obtained. 

Mycetoma,  also  called  Madura  foot  or  fungus  foot  of  India,  is  due  to 
a  parasite  possessing  the  general  characters  of  other  members  of  the 
actinomyces  group,  called  the  Streptothrix  madurae.  Two  forms 
of  the  disease  have  been  recognized,  one  in  which  the  discharged 
granules  are  black  (gunpowder  grains)  and  the  other  in  which 
thev  are  white  or  yellow  (ochroid).  Laveran^  believes  that  the  two 
varieties  are  distinct,  and  that  both  differ  from  the  ordinary 
actinomyces  of  man  and  cattle;  he  would  make  the  streptothrix  myce- 
toma a  distinct  parasite. 

De^nonstration. — The  parasite  may  be  identified  in  the  tissues  or 
discharges  bv  a  method  similar  to  that  recommended  for  actinomyces. 
The  ochroid  and  melanoid  granules  may  be  crushed  and  examined  under 

'  "M6d.  Mod.,"  Tune  10,  1903,  p.  181.  . 

»  •Bull,  flc  I'Acad.  de  MM,"  190.3,  vol.  xlvii.  p.  773. 


lyo  GENERAL  PATHOLOGY. 

the  microscope,  when  mycehal  threads  will  usually  be  recognized. 
There  is  a  similar  ray-like  gro^\^h  with  slight  enlargement  at  the  ends 
of  the  filaments,  but  not  the  typical  clubs  of  actinomyces. 

Usually  but  one  foot  is  affected.  Both  macroscopically  and  micro- 
scopically the  lesion  resembles  actinomycosis,  and  is  essentially  chronic, 
often  persisting  for  years.  It  is  a  slowly  spreading  inflammatory  process, 
characterized  by  the  formation  of  granulation  tissue  in  which  necrotic, 
degenerative,  and  suppurative  processes  occur;  the  overlying  skin 
breaks,  giving  rise  to  sinuses  from  which  a  serous  or  serosanguineous 
discharge  escapes.  It  commonly  begins  in  the  sole  of  the  foot  or  in  a 
toe,  and  rarely  extends  beyond  the  ankle;  the  bones  soften  and  necrose, 
and  even  such  dense  structures  as  tendon  and  ligament  yield  before  the 
advancing  granulation  tissue.  The  parasite  shows  practically  no 
tendency  toward  generalization. 

Streptothricosis  is  commonly  used  to  cover  all  lesions  produced  by 
fungi  resembling  the  streptothrix,  usually  including  infections  by  the 
actinomyces.  The  most  important  type  of  streptothrix  infection  not 
already  considered  is  that  involving  the  lung — pulmonary  streptothri- 
cosis. Warthin  and  Olney^  have  recently  reported  a  case  and  collated 
others  from  literature.  The  acid-fast  branched  threads  are  abundant 
in  the  sputum,  which  may  also  yield  cultures.  Similar  streptothrix 
elements  may  be  found  in  the  sputum,  coming  from  large  tubercular 
cavities,  dilated  bronchi,  or  gangrenous  areas  in  the  lungs;  in  many 
of  these  cases  the  infection  is  clearly  secondary;  it  may  intensify 
previous  lesions  or  give  rise  to  independent  extension. 

Leptothricosis^  is  an  infectious  process  due  to  invasion  of  the  tissues 
by  members  of  the  leptothrix  group.  The  botanical  position  of  these 
germs  is  even  less  accurately  determined  than  that  of  the  actinomyces, 
from  which  they  dift'er  in  that  true  branching  is  not  present.  In  one 
of  Pearce's  cases  the  parasite  was  the  only  organism  present  in  gall- 
stones. Mycosis  tonsillaris  benigna  and  Pharyngomycosis  leptothrica 
are  names  applied  to  a  chronic  infection  involving  the  tonsils,  pharynx, 
or  base  of  the  tongue;  rarely  the  larynx  and  esophagus  are  affected. 
In  this  condition  the  whitish  patches  on  the  surface,  or  the  plugs  ex- 
tending into  the  tonsil,  are  composed  largely  of  leptothrix  mycelia. 
The  organism  may  readily  be  detected  by  the  usual  anilin  dyes,  but 
is  not  easilv  cultivated. 


SACCHAROMYCETES.' 

Blastomycosis  or  Saccharomycosis,  preferably  the  former,  is  applied 
to  diseases  produced  by  yeasts.  These  bodies,  well  known  in  the  arts, 
consist  of  oval,  round,  or  nearly  spheroidal  cells  of  varying  sizes,  com- 
monly slightly  larger  than  a  red  blood-cell.  Proliferation  by  budding 
is  the  usual  method  of  reproduction,  and  if  the  Saccharomyces  cere- 
visicB — ordinary    domestic   yeast — be   watched    under   the   microscope, 

'  "Amer.  Jour,  of  Med.  Sci.,"  vol.  cxxviii,  p.  637. 

^  Leptothrix  infection  in  man  and  animals  has  been  considered  in  detail 
by  Pearce,  "Univ.  of  Penna.  Med.  Bull.,"  Aug.,  1901,  and  November,  1902; 
full  bibliography. 

'  "Centralbl.  f.  Bakt.,"  Aug.  19,  1904,  p.  529.  An  elaborate  systematic 
classification  of  the  Saccharomycetes.  Guilliermond,  "Bull,  de  I'lnst.  Pasteur," 
March  15,  1905,  p.  178. 


BACTERIA   AS   CAUSES  OF  DISEASE. 


171 


the  toniKition  of  buds  which  cnhirgc  and  j^ive  rise  to  new  cells  can  readily 
be  recognized.  Often  the  new  cell  adheres  to  the  parent,  and  by  con- 
tinuation of  this  process  short  chains  and  irregular  groups  are  ff)rmed. 
Most  yeasts  may  be  cultivated  on  all  the  laboratory  media,  and  grow 
especially  well  on  nutrients  containing  sugar,  whieh  they  ferment  with 
the  production  of  alcohol.  HiK-hner  has  shown  that  the  activity  of 
yeasts  depends  upon  a  ferment  containetl  in  the  interior  of  the  cell; 
this  substance  he  has  expressed  from  the  plant  and  utilized  for  the 
production  of  fermentation. 

With  regard  to  the  pathogenic  action  of  yeasts  in  man  our  informa- 
tion is  incomplete  ;  they  are  sometimes  found  in  the  stomach,  occasion- 
allv  in  the  stools,  and  Bendeler'  has  shown  that  they  may  occur  in  the 
urine.  Recently  Klein  and  Gordon-  have  reported  an  epidemic-  affec- 
tion of  the  throat  resembling  diphtheria,  tonsillitis,  and  scarlet  fever, 
but  apparently  due  to  a  yeast,  which  they  call  the  Saccharomyccs  liowi- 
}ns.  Yeasts  have  been  found  in  tumors,  and  certain  observers  believe 
them  to  be  a  cause  of  neoplasm.'' 
The  Saccharomyces  neoformans  has 
not  been  generally  received  with 
enthusiasm,  and  the  observations 
of  Sanfelice  still  lack  confirmation. 
Cleary^  reports  a  case  of  generalized 
blastomycosis,  and  collates  four 
others  from  literature.  When  the 
parasite  enters  the  circulation,  pul- 
monary localization  is  an  almost 
constant  phenomenon. 

The  name  blastomycetic  derma- 
titis' is  applied  to  a  form  of  cutaneous 
blastomycosis  due  to  a  pleomorphous 
organism  resembling  and  usually 
classed  with  the  yeasts.  In  the 
tissues  and  discharges  the  parasite  is 
found  as  a  spherical  cell  10  ,"  to  i  5  ," 
in  diameter,  double  contoured,  often 
budding,  and  sometimes  containing 

intracellular  structures  that  may  be  spores  ;  it  grows  best  on  beerwort, 
glycerin  and  glucose  agars,  which"  should  be  slightly  acid.  Successful  cul- 
tures develop  in  from  two  to  sixteen  days,  and,  according  to  Ricketts,  on 
agar,  or  beerwort  agar  slants,  may  be  (i)  a  smooth,  whitish,  pasty  growth 
without  aerial  hypha?,  and  may  or  may  not  penetrate  the  medium.     In 


Fic.    94.— Vkast    Cklls    from    Pubk    Clxivkc. 
BuDDrNc;  Forms  ark  I'rksknt. 


'  "Centralbl.  f.  Bakt.,"  Jan..  1905,  p.  55. 

of   the 


'Thirty-second    Annual    Report 


Local    Government     Board.     1004. 


P-  550. 


''Sanfelice  has  been   a  most  ardent  advocate   of  this  view;    his  extensive 
observations  and  writings  on  the  subject  may  be  traced  from  his  papers  in  the 
"Rif.  Med,"  Sept.  0.  1902.  and  "Zeit.    f.  Hyg.     Infcctkrank.,"   1903,    Bd 
p.  64. 

*  "Trans.  Chicago  Path.  Soc."  May.  1904.  P-  105. 

'  Mont  gome  r\-,  "Jour.    Amer.   Med.  Assoc."    Tunc  7.   190?.     Wilder. 
Amer.  Med.  Assoc.."' Dec.  .31.  1904.     Sequcira.  "Brit.  Jour,  of  Dermat  .  ' 
1903,  p.   12  1.     Koehler  and    Hall.  "Jour,  of  Cutaneous    Diseases."    Die  , 
Gilchrist,  "Johns  Hopkins  Hosp.  Bull."  Feb..  1904. 


xliv, 


'Jour. 
.\pril. 
1904. 


172  GENERAL  PATHOLOGY. 

this  form  budding  is  usually  conspicuous,  although  mycelial  growth  is 
often  present.  ( 2 )  The  surface  is  granular  or  plicated ;  sometimes  spicules 
extend  upward,  but  aerial  hyphae  are  absent.  (3)  Growths  resembhng 
either  of  the  first  groups,  but  conidia  with  aerial  hyphse  are  also  present.^ 
Gilchrist  believes  that  the  second  and  third  forms  are  identical. 

Alorbid  Anatomy. — The  disease  is  a  chronic  inflammatory  process, 
primarily  local,  developing  as  a  papule  which  becomes  a  pustule  covered 
by  crusts.  It  extends  laterally  by  the  formation  of  minute  dermal  and 
subdermal  abscesses  which  usually  are  of  microscopic  dimensions.  Ex- 
tensive hyperplasia  is  present  in  the  rete,  the  cells  of  which  can  pro- 
ject into  the  corium.  Mast-cells  and  giant-cells  are  frequently  present, 
the  latter  often  containing  parasites.  The  organisms  can  be  recog- 
nized in  sections  stained  with  hematoxylin  and  eosin,  but  better  results 
are  obtained  with  methylene-blue.  The  fungus  may  be  demonstrated 
by  placing  fresh,  hardened,  or  teased  particles  of  tissue,  or  pus,  on  a  sHde, 
dropping  on  a  ten  to  thirty  per  cent,  solution  of  potassium  hydrate  or 
equal  parts  of  liquor  potassae  and  glycerin,  and  applying  a  cover-glass. 
In  such  preparations  the  organisms  appear  as  double-contoured,  highly 
refractile  bodies,  in  some  of  which  granular  contents,  vacuoles,  or 
shining  spore-like  bodies  can  be  demonstrated  (Montgomery). 


SPIROCH-^TA. 

There  are  a  number  of  diseases  occurring  in  man  in  which  spiral 
organisms  of  an  imperfectly  determined  nature  are  found.  Usuallv 
these  parasites  have  been  grouped  with  the  bacteria,  but  the  recent 
studies  of  Schaudinn-  strongly  controvert  this  view  and  place  them 
with  the  animal  parasites,  making  them  closely  related  to  the  try- 
panosomes.  Parasites  of  this  type  have  been  found  in  the  owl  and  the 
goose.  In  man  the  diseases  in  which  spiral  organisms  of  this  kind  have 
been  found  are  relapsing  fever,  Vincent's  angina, 
and,  more  recently,  syphilis.    From  none  of  these  has 

Vthe  organism  been  obtained  in  pure  culture. 
Relapsing  fever ^  is  due  to  an  actively  motile,  deli- 
v-v^  v^-^^         cate,  flexible  spiral  organism,  16  !>-  to  40  //  in  length 
^/vP^Vrf^  and  of  scarcely  measurable  thickness.     The  number 

^J"^^  ^^  of  complete  spirals  in  one  organism  may  be  from  ten 

,^— "^^  to  fifteen.      According  to   Sandwith,   the   motion  is 

Pj       -  _  s  chiefly  lateral  and  rotary.     The  parasite  may  be  so 

'  o  B  E  R  M  E I  E  R  I     actlvc  that  it  is  with  difflcultv  kept  in  the  field  of  the 

(Spirillcm    of   Re-       rniVrncirnnP 
LAPSING     Fever).—       miCrOSCOpC. 

)<&^"c5^efeTs'"''''  Demonstration. — During  the  crisis  the  organisms 

are   present  in  the  blood  in  large  numbers.     They 

are  less  abundant  just  before  the  occurrence  of  the 

crisis,   and   after   it   is   past    they    disappear    rapidly.     They    are    not 

present  in  the  peripheral  circulation  during  the  nonfebrile  period.     In 

^  Ricketts,  "Trans.  Chicago  Path.  Soc,"  May  9,  1904,  p.  113. 

'"Generations  und  Wirtswechsel  bei  Trypanosoma und  Spirochaete,"  Arbeit. 
a.  d.  kais.  Gesundheitsamte,  Bd.  xx,  H.  3,  1904,  pp.  387-439. 

^ Quite  full  references  to  the  older  articles  will  be  found  in  Allbutt's  "Sys- 
tem of  Medicine."  vol.  i,  p.  958.  See  also  recent  paper  by  Sandwith,  "Practi- 
tioner," May,  1904,  p.  653. 


BACTERIA   AS  CAUSES  OF    DISEASE. 


'7.? 


order  to  demonstnitc  the  presence  of  the  organism  in  the  Moinl,  the 
rtnger  or  lobe  of  the  ear  is  properly  cleansed,  disinfected,  and  pricked 
by  a  needle.  (See  Part  III,  chapter  on  Diseases  of  the  Blood.)  A 
drop  of  blood  is  received  on  a  slightly  warmed  slide  and  a  cover-glass 
is  at  once  applied.  As  soon  as  the  blood  flows  near  the  margin  of  the 
cover-glass  a  ring  of  oil  or  vaselin  should  be  ])ainted  around  the  cover- 
glass  in  order  to  prevent  too  rapid  drying  tluring  the  progress  of  the 
examination.  As  the  organism  jjossessed  a  transverse  diameter  approxi- 
mately that  of  the  cholera  spirillum,  it  will  l)e  necessary  to  conduct  the 
examination  with  high  powers.  The  presence  of  spirilla  is  indicated 
by  the  agitation  of  the  corpuscular  elements.  At  first  the  spirals  may 
be  too  active  to  be  readily  focused  upon,  but  in  a  short  time  they  be- 
come sufficiently  quiet  to  permit  examination.  Just  before  and  during 
the  crisis  the  number  of  spirilla  may  approach  one  organism  for  every 
twenty  erythrocytes.  After  the  disappearance  from  the  ]jeripheral 
circulation  Metchnikoff  has  succeeded  in  demonstrating  them  in  the 
splenic  pulp.  In  moist  films  or  in 
suspension  in  normal  salt  solution 
the  motility  may  be  evident  for 
twelve  hours  or  longer.  The  organ- 
ism is  evidently  destroyed  by  a 
comparatively  low  temperature,  a 
fact  which  has  been  taken  to  indi- 
cate the  absence  of  spores,  but  also 
supporting  the  belief  that  it  belongs 
with  the  animal  parasites.  Dry 
films,  prepared  as  described  in  the 
chapter  on  The  Blood,  may  be 
stained  as  directed  for  other  bac- 
teria. It  is  probable  that  the 
spirillum  of  relapsing  fever  will 
stain  by  the  same  methods  as  the 
organism  found  in  syphilis,  and 
also  by  Wright's  method.  It  can 
also  be  tinged  by  aqueous  solutions 
of  gentian-violet,  Bismarck  brown, 
or  fuchsin. 

Pathogenesis. — The  parasite  is  always  demonstrable  in  some  stage 
of  relapsing  fever;  with  the  advancing  pyrexia  the  organisms  increase, 
and  disappear  during  defervescence.  The  disease  may  be  transmitted 
to  man  and  monkeys  by  inoculation  with  the  infected  blood.  When 
death  has  resulted  from  relapsing  fever,  the  skin  commonly  shows  a 
characteristic  yellowish  hue.  Various  changes— fatty  and  granular — 
have  been  described  in  the  heart;  the  spleen  is  enlarged  and  softened, 
the  follicles  swollen,  and  the  pulp  darker  than  normal.  The  liver  may 
be  enlarged,  the  cells  fatty  and  granular,  and  in  some  cases^  round- 
cell  infiltration  in  the  neighi)orhood  of  the  portal  vein  occurs.  Granular 
and  fatty  changes,  sometimes  with  hemorrhages,  are  found  in  the  kidney. 
In  some  cases  the  interstitial  tissue  is  infiltrated,  but  the  change  is  not 
characteristic. 

Ulcero-raembranous   stomatitis    or   angina,   also   called   diphtheroid 


Fic.  96.— Spirillum  of  Vi.nte.vt  and  the  Fusi- 
form Baollus;  Othkr  Organisms  are  also 
Present. — (From  case    rtporltd  by   Or.  Rostn- 

bfrgfr.) 


174 


GENERAL  PATHOLOGY. 


angina  and  angina  of  Vincent/  is  a  disease  affecting  particularly  the 
tonsils  and  uvula,  less  commonly  the  oral  and  pharyngeal  mucosa 
or  lips;  it  is  characterized  by  the  formation  of  a  superficial  membrane, 
and,  in  marked  cases,  necrosis  extending  into  the  submucosa.  In  severe 
infection  parts  of  the  uvula  may  be  destroyed.  The  membrane  is  vellow, 
or  greenish-yellow,  and  when  detached  leaves  a  bleeding  or  eroded  sur- 
face; glandular  enlargement  is  variable.  The  actively  motile  spiro- 
chasta  varies  in  length  from  lo  //  to  30  //,  and,  like  the  organism  found  in 
relapsing  fever,  is  extremely  tenuous  and  never  stains  with  the  same 
intensity  as  the  symbiotic  bacillus.  The  spirillum  is  usually  associated 
with  a  fusiform  rod-shaped  organism  (Bacillus  fusiformis)  5  /«  to  10  //  in 
length  and  0.6  /^  at  its  widest  point.  The  bacillus  stains  by  Gram's 
method,  the  spirillum  does  not.  Wright  believes  that  the  fusiform 
organism  is  not  a  bacillus,  and  calls  attention  to  the  fact  that  the  incessant 
whip-like  movements  of  the  spirillum  vividly  recall  the  actively  moving 
flagellate  bodies  seen  in  malarial  blood;  he  suggests  that  both  organisms 

may  be  modifications  or  stages  in  the 
evolution  of  the  same  parasite. 

Syphilis^  is  a  chronic  infectious 
disease  the  exact  cause  of  which  has 
eluded  accurate  determination.  Lust- 
garten  described  a  bacillus  to  which  he 
attributed  the  disease.  Other  bacteria 
alleged  to  be  the  specific  causes  of 
syphilis  have  been  brought  forward  by 
de  Lisle  and  Jullian,  Joseph  and  Pior- 
kowski,  and  others;  Schuller  describes 
an  animal  parasite  which  he  believes  to 
be  the  cause.  The  relation  of  these 
organisms  to  syphilis  is  far  from  estab- 
lished, and  at  present  the  tendency  is 

Case    of 

'  See    works    referred    to    in    foot-note, 
p.   Si;     also    Rosenberger,    "Anier.    Med.," 
July   23,    1904,    p.    161;     Bruce,    "Lancet," 
July   16,    1904,    p.    135;   Wright,   "Lancet," 
July    9,    1904;     Veszpremi,    "Centralbl.    f.    Bakt.,"    Bd.    xxxviii,    1905,    p.    136, 
"Cultivation    and    Animal    Experiments    on    the    Bacilkis   fusiformis  and  Asso- 
ciated Spirillum." 

^  References  to  bacteriology  of  syphilis  can  be  obtained  from  the  current 
works  named  in  the  foot-note  on  p.  Si.  "Successful  Inocvilation  of  Syphilis 
on  Apes,"  see  Metchnikoff  and  Roux,  Third  Memoir,  "Annales  de  I'lnst.  Pas- 
teur," Nov.  25,  1904,  p.  657,  where  reference  to  their  own  and  other  previous 
studies  may  be  found;  also  Lassar,  "Dermatolog.  Zeit.,"  xi.  No.  8;  Neisser, 
"Deut.  med.  Woch.,"  1904,  p.  1369;  Zabolotny,  "Arch.  sci.  Biol.,"  vol.  xi,  Nos. 
I  and  2,  p.  155;  full  discussion  before  Tenth  Congress  of  Dermatology,  Berlin, 
Sept.,  1904;  Salmon,  "C.  R.  Soc.  de  Biol.,"  June  11,  1904;  Arnal  and  Salmon, 
"Annales  de  ITnst.  Pasteur,"  July  25,  1904;  Tomasczewski,  "Deut.  med.  Woch.," 

1903,  No.  26;  Hoffmann,  "Berl.  klin.  Woch.,"  Feb.  6,  1905,  and  Queyrat,  "Soc. 
med.    des   Hop.,"   Jan.    13,    1905.      Piorkowski,    "Berl.   klin.   Woch.,"   Sept.     19, 

1904,  "Successful  Inoculation  of  a  Horse."  Klingmiiller  and  Baermann,  "Deut. 
med.  Woch.,"  1904,  "Non-filterability  of  Syphilitic  Virus."  For  recent  study 
of  immunity  in  syphilis  see  Nagelschmidt,  "Ueber  Immunitat  bei  Syphilis  nebst 
Bemerkungen  ttiber  Diagnostik  und  Scrotherapie  der  Syphilis,"  Berlin,  1904. 
Literature  of  the  recent  work  on  the  spirochaeta  of  syphilis  is  given  in  full  by 
Flexner  and  Noguchi,  "Med.  News,"  June  17,  1905,  p.  1145;  also  McWeeney, 
"Brit.  Med.  Jour.,"  June  10,  1905,  p.  1262. 


Fig.    97. — Spiroch.eta     from     a 
Syphilis  — {McWeeney.) 
A,  A.    Pairs  united  at  one  end     B,  B.  Twisted 
forms.    C.   Double  length  forms. 


BACTERIA    AS   CAUSES  OF   DISEASE.  I  75 

to  look  with  favor  upon  the  Spirochaeta  pallida  discovered  by  Schaudinn 
and  Hoffmann.  This  organism  has  been  identilied  in  syphilitic  lesions, 
both  natural  and  experimental,  and  has  not  been  found  in  any  other 
infection.  The  organism  may  also  be  found  in  the  fluids  aspirated  from 
enlarged  glands  and  in  the  curetings  and  expressed  juices  of  the  initial 
lesion.  It  is  4  ,"  to  14  ,"  in  length  and  does  not  exceed  0.5  /^  in  diam- 
eter; it  is  actively  motile,  rotating  on  its  axis,  bending,  shortening,  and 
lengthening  the  spirals.  In  some  organisms  a  suggestion  of  an  undulat- 
ing membrane  has  been  observed;  flagclla  have  not  been  demonstrated. 
In  the  superficial  lesions  of  syphilis  the  parasite  is  associated  with  a 
larger  and  more  readily  stained  spirochaeta  (Spirochaeta  refringens); 
the  latter  has  not  been  found  in  the  deeper  syphilitic  lesions. 

Demonstration. — The  organism  is  difficult  to  stain;  indifferent  results 
are  obtamed  by  the  use  of  anilin-oil-gentian-violet  solution,  and  most  of 
the  ordinary  bacterial  stains  are  unsatisfactory.  For  its  demonstration 
the  discoverers  recommend  the  following:  Giemsa's  eosin  solution 
(2.5  c.c.  of  a  one  per  cent,  solution  of  eosin,  in  500  c.c.  of  water),  12  parts; 
azure  I  (i  to  1000  aqueous  solution),  3  parts;  azure  II  (0.8  to  1000  aque- 
ous solution),  3  parts;  the  prepared  stain  does  not  keep.  Air-dried, 
thinly  spread  films  are  fixed  in  absolute  alcohol  for  ten  minutes  and  left 
in  the  stain  twenty-four  hours,  washed  in  water,  dried  in  the  air.  and 
examined  in  cedar  oil. 

Syphilis  may  be  inherited  or  acquired.  Hereditary  syphilis  may  re- 
sult from  parental  infection  of  the  ovum  or  spermatozoon,  or  the  mother 
may  infect  the  fetus  by  syphilis  acquired  after  impregnation.  Syphilis 
transmitted  to  the  child  during  delivery  is  an  acquired  form  of 
the  disease. 

Syphilitic  poison  exerts  a  deleterious  influence  on  the  developing 
infant,  which  as  a  result  not  uncommonly  dies;  fibroid  and  thrombotic 
processes  occur  in  the  placenta  or  maternal  sinuses  and  interfere  with 
proper  nutrition  of  the  child.  A  large  percentage  of  syphilitic  women 
abort;  when,  however,  the  offspring  survives,  it  is  usually  ill-nourished, 
wasted,  and  may  be  bom  with  some  of  the  external  manifestations  of 
syphilis,  or  these  may  develop  later.  At  birth  there  may  be  numer- 
ous blebs  on  the  skin  with  areas  in  which  the  surface  is  excoriated, 
resembling  the  cutaneous  maceration  seen  in  still-born  infants.  A 
catarrhal  rhinitis  (snuffles)  and  other  disturbances  of  the  mucous  mem- 
branes may  be  present.  The  pathognomonic  eruption  of  hereditary 
syphilis  is  a  pemphigus,  which  may  be  present  at  birth;  in  the  affected 
areas  the  epidermis  is  elevated,  giving  rise  to  characteristic  blebs  con- 
taining a  sanguinolent  or  greenish  fluid.  Pustular  eruptions  resembling 
the  skin  lesions  of  variola  sometimes  occur.  The  vesicular  pemphigus 
is  most  frequent  on  the  palms  and  soles,  and  the  pustular  form  on  the 
buttocks  and  around  the  genitalia;  erythematous  rashes  are  common. 
Paronychia,  dactylitis,  and  interstitial  keratitis  further  illustrate  the 
protean  nature  of  the  affection.  A  characteristic  form  of  osteochon- 
dritis develops  in  the  epiphyseal  junction  of  the  long  bones.  On  section, 
these  structures,  particularly  the  lower  end  of  the  femur,  the  apophyso- 
epiphyseal  junction,  is  l)roadened,  yellowish  in  color,  and  mav  contain 
areas  of  pus-like  softening;  this  condition  is  called  syphilitic  osteo- 
chondritis. Microscopically  the  zone  of  <leveloping  bone  is  broadened, 
irregular,  contains  an  excess  of  embr\-onal  and  giant  mil-    nn,l  ivlnli. 


176  GENERAL  PATHOLOGY. 

at  first  the  calcific  deposit  is  excessive,  later  calcification  ceases  and 
the  previously  deposited  lime  salts  may  be  absorbed.  The  epiphyses 
may  be  enlarged  and  occasionally  they  separate  from  the  shafts  (epi- 
physeolysis).  Marfan  found  that  in  one-half  of  the  cases  of  congenital 
syphilis  the  spleen  is  increased  in  size,  and  that  splenic  enlargement 
in  infants  is  most  commonly  due  to  syphilis.  The  liver  in  hereditary 
syphilis  is  usually  larger  than  normal  as  a  result  of  diffuse  interstitial 
hepatitis  with  or  without  gummata.  Stoerk^  reports  an  instance  of 
renal  hypoplasia  attributed  to  congenital  syphilis.  Massalongo^  and 
Guthrie^  have  reported  chronic  interstitial  nephritis  due  to  congenital 
syphilis.  Coupland^  and  Stroeb^  record  instances  of  acute  interstitial 
nephritis  in  congenital  syphilis;  Speiss^  found  renal  disease  in  ten 
of  thirty-four  syphilitic  children.  Barlow,^  Chiari,^  and  others 
have  reported  true  arteritis  occurring  in  congenital  syphilis  and  lead- 
ing to  various  visceral  alterations  due  to  interference  with  blood-supply. 
The  teeth  erupt  irregularly,  develop  unevenly,  are  structurally  altered, 
and  frequently  decay  early.  One  of  the  most  characteristic  lesions  of 
hereditary  syphilis  is  seen  in  the  upper  permanent  median  incisors. 
These  are  peg-like,  short,  and  the  cutting-edge  marked  by  a  crescentic 
excavation.  According  to  Paton,^  hereditary  syphilis  may  cause  the 
following  joint  manifestations:  (i)  simple  synovial  effusion;  (2)  joint 
disease  associated  with  syphilitic  epiphysitis;  (3)  primary  gummatous 
infiltration  of  the  synovial  membrane;  (4)  osteitis  associated  with 
effusion  only;  (5)  osteitis  with  gummatous  disease  of  the  synovial 
membrane;  this  variety  has  been  termed  pseudo-white-swelling;  (6) 
deforming  arthritis  or  "the  deforming  arthropathy  of  Fournier.  Orch- 
itis was  present  in  5  of  Still's '"  64  cases.  Oligocythemia  and  oligochro- 
memia  are  commonly  marked.  Mucous  patches  are  almost  always 
present  and  deep  refractory  fissures  at  the  angle  of  the  mouth  may, 
on  healing,  leave  radiating  scars. 

Fournier's"  recent  statistics  show  what  a  disastrous  influence  syphil- 
itic poison  exerts  on  gestation  and  on  the  infant.  In  366  pregnancies 
there  were  115  abortions,  and  174  of  the  infants  born  alive  died  during 
the  first  years  of  life;  31  (8.5  per  cent.)  of  the  remainder  were  in  good 
health.  In  45,  mental  and  physical  development  was  retarded;  43 
showed  lesions  of  the  skeleton;  in  42  there  was  ocular  disease.  The 
nervous  system  was  affected  in  39.  He  also  records  19  observations 
clearly  establishing  that  inherited  syphilis  may  be  transmitted  to  the  off- 
spring. Of  the  333  pregnancies  recorded  by  Neumann, ^^  156  termin- 
ated in  abortion;  24  children  were  still-born,  43  were  syphilitic,  and 
79  showed  no  evidence  of  the  disease. 

^  "Wien.  klin.  Woch.,"  1901,  No.  41. 
2  International  Congress,  Rome,  1894. 

*  Report  of  the  Society  for  the  Study  of  Diseases  in  Children,  1901,  p.  69. 

*  "Trans.  Path.  Soc.  of  London,"  1876,  vol.  27,  p.  303. 
^  "Centralbl.  f.  allg.  Path.,"  1891,  vol.  ii,  p.  1009. 

*  Inaug.  Diss.,  Berlin,  1877. 

^  "Trans.  Path.  Soc.  of  London,"  vol.28,  p.  287. 

8  "Wien.  klin.  Woch.,"  1898. 

'  "Brit.  Med.  Jonr.,"  Nov.' 28,  1903,  p.  1389. 

'"  "Lancet,"  Nov.    19,   1904. 

"  "Societe  Francaise  de  Dermatologie  et  de  Syphiligraphie,"  July  6,  1904. 

*^  "Wien.  klin.  Woch.,"  No.  20,  1904,  p.  262. 


nACTERIA   AS   CAUSKS  OF   OlSKASK 


Altliough  acquired  syphilis  is  essentially  a  venereal  disease,  Huekley' 
has  been  able  to  collect  over  9000  cases  of  extragenital  infection.  In 
4634  cases  of  syphilis  Xeuniann-  found  207  instances  of  extragenital. 
and  157  of  perigenital  chancre;  of  the  former.  106  were  on  the  lips  and 
27  on  the  hands. 

Syphilitic  manifestations  may  be  grouped  in  seven  stages:  (i)  local 
incubation,  (2)  period  of  initial  lesion,  (3)  secondary  or  systemic  incuba- 
tion, (4)  period  of  secondary  symptoms,  (5)  intermediate  period.  (6) 
tertiary  period,  (7)  period  of  jiarasyphilitic  manifestations.  These 
arbitrarv  divisions  commonly  made  by  systematic  writers  are  convenient 
for  descriptive  purposes,  but  often  the  disease  is  disinclined  to  follow 
them.  The  period  of  incubation  varies  from  ten  days  to  six  weeks, 
averaging  about  three  weeks.  The  secondary  symptoms  come  on  in 
about  six  weeks  to  two  months  after  the  beginning  of  the  chancre,  and 
last  from  two  weeks  to  three  years.  The  intermediate  period  is  of 
indefinite  duration  and  often  absent.  The  tertiary  and  parasyphilitic 
manifestations  are  essentially  late  and  permit  of  no  trustworthy  state- 
ment as  to  their  duration.  The  lesions  occurring  in  the  i)arasyphilitic 
stage  of  syphilis  are  differentiated  from  all  the  earlier  manifestations 
by  the  fact  that  they  are  uninfluenced  by  the  usual  antisyphilitic  reme- 
dies. 

Morbid  Anatomy. — The  initial  lesion  of  syphilis — the  chancre — 
occurs  at  the  point  of  inoculation,  and  is  usually  solitary,  although 
Pierron^  records  an  instance  of  six  separate  chancres  on  the  penis. 
Quevrat*  reported  a  casein  which  ii  chancres  developed  in  succession. 
Metchnikoff  inoculated  an  ape  on  October  26  and  again  on  November  5. 
1904;  a  chancre  at  the  point  of  first  inoculation  appeared  in  twenty-six 
davs.  and  a  second  chancre  followed  twenty  days  after  the  second 
inoculation.  These  and  similar  observations  go  to  show  that  insus- 
ceptibility to  further  infection  is  not  coincident  with  the  appearance 
of  the  initial  lesion. 

Histologically  the  chancre-'  consists  essentially  of  a  new  growth  in  the 
skin  or  mucous  surface,  followed  by  hyaline  degenerative  and  necrotic 
processes,  which  usually  terminate  in  ulceration.  The  first  changes 
occur  at  the  point  of  infection,  and  consist  of  slight  edema  which  be- 
comes more  marked  and  contains  demonstrable  fibrin;  this  serous 
exudate  extends  into  the  underlying  connective  tissue  and  is  promj.tly 
followed  bv  a  cellular  infiltration  composed  of  plasma  and  typical  lymph- 
oid cells,  and  round  cells  containing  vesicular  nuclei;  in  the  absence  of 
mixed  pvogenic  infection  polymorphonuclear  leukocytes  are  not  present. 
The  cellular  accumulation  is  most  conspicuous  around  the  capillaries  and 
small  veins,  in  both  of  which  thromln  form;  the  vascular  endothelium 
proliferates.  Over  the  center  of  the  chancre  the  epidermal  strata  are 
thinned,  while  at  its  margin  the  epithelium  proliferates.  The  mass 
is  now  an  indurated  node  the  firmness  of  which  constitutes  one  of  its 
most   characteristic   features,   hence   the   name   "hard    chancre."     The 

'  'Svphilis  of  the  Innocent,"  p.  30 

»  "\Vien.  klin.  Woch.,"  Sept.  25.  iqoj.  p.  looi. 

"  "Arch,  de  Med.  et  dc  Phann.  Mil.."  No.  2,  190; 

*  "Lancet."  Sept.  lo.  1904.  p.  779.  . 

*  Recent  literature  on  histology  of  chancre,  see  Amal  and  Salmon.  Ann 
de  rinst.  Pasteur,"  lulv  2^,  1904.  p'  465.  Ehrman.  "Arch.  d.  Dinnat  ii  Syph  . 
1904,  Ixviii,  No.  i;   Bosc,  "C.  R.  Soc.  de  Biol.  "  1904.  vol.  57.  p.  104 

13 


178  GENERAL  PATHOLOGY. 

extreme  hardness  of  the  mass  is  often  useful  to  differentiate  the  lesion 
from  ulcerative  or  inflammatory  processes  arising  from  other  causes. 
When  the  process  is  associated  with  a  mixed  infection,  inducing  more 
or  less  rapid  liquefaction  of  the  proliferate,  induration  is  sometimes  in- 
conspicuous, or  may  even  be  absent.  The  view  that  absence  of  indura- 
tion is,  to  a  certain  extent,  dependent  upon  the  character  of  the  tissue 
infected,  does  not  seem  to  be  tenable,  as  so  distinguished  an  observer 
as  Hutchinson  maintains  that  any  tissue  may  suffer  induration,  and 
that  chancre  in  any  area  is  commonly  associated  with  the  occurrence  of 
this  phenomenon.  As  the  blood-vessels  are  the  seat  of  endothelial  pro- 
liferation and  thrombosis,  the  blood-supply  is  proportionately  lessened, 
leading  to  liquefaction  necrosis  of  the  overlying  epithelium;  an  ulcer 
does  not  always  form,  licpefaction  necrosis  does  not  always  occur, 
and  occasionally  a  chancre  will  be  observed  in  which  the  epithelial 
covering  remains  unbroken.  When  ulceration  does  occur,  a  cup-like 
or  scooped-out  ulcer  forms,  its  edges  are  not  undermined,  and  it  is  not 
likely  to  be  sloughing  or  phagedenic.  With  the  subsidence  of  cellular 
infiltration,  repair  begins;  the  fluid  exudate  and  cells  are  removed, 
fibroblasts  are  formed,  and  gradually  resolution  is  accomplished. 

Associated  with  the  initial  lesion,  the  nearest  anatomic  lymph- 
nodes  show  the  alterations  incident  to  infection.  In  some  instances 
the  local  lymphatic  involvement  usually  manifested  during  the  activity 
of  the  initial  lesion  escapes  observation,  or,  possibly  it  is  not  present. 
During  this  process  the  lymphoid  structures  proliferate  and  become 
more  or  less  edematous,  thereby  bringing  about  induration  and  con- 
siderable enlargement  of  the  lymph-nodes  functionally  nearest  the 
initial  lesion.  If  pyogenic  bacteria  gain  ingress  through  the  ulcer  or 
by  other  routes,  the  glandular  swelling  and  hyperplasia  may  terminate 
in  suppuration;  when  suppuration  does  not  ensue,  which  is  usually  the 
case,  the  infiltration  and  induration  gradually  subside. 

Following  the  phenomena  just  described,  a  stage  of  apparent  quies- 
cence ensues,  which,  as  in  other  infective  diseases,  constitutes  the 
period  of  systemic  incubation.  This  persists  for  from  ten  days  to  six 
months;  the  extremes  given  are  unusual,  the  secondary  phenomena 
commonly  manifesting  themselves  in  about  six  weeks.  The  lymph- 
nodes  (it  is  probable  that  all  the  lymphatic  structures  participate ;  cer- 
tainly, all  that  can  be  discerned  from  the  surface)  show  a  varying  amount 
of  induration  and  swelling;  not,  however,  manifesting  any  tendency 
to  suppuration.  The  affected  lymph-nodes  are  freeh^  movable,  show 
no  tendency  to  become  confluent  or  adherent  to  adjacent  structures, 
and  vary  in  density  from  relatively  soft  masses  to  extreme  induration. 
Syphilis  has  now  passed  into  the  secondary  stage,  and  multiple  cutaneous 
lesions  occur;  these  are  clinically  important,  but  pathologically  they 
are  not  essentially  different  from  many  skin  lesions  that  arise  independent 
of  syphilis.  Syphilitic  eruptions  are  commonly  characterized  by  their 
polymorphism  and  their  symmetric  distribution.  The  exanthem  is 
not  restricted  to  the  skin,  but  appears  also  on  the  mucous  membranes. 
The  cutaneous  and  mucous  lesions  of  secondary  syphilis  usually  involve 
the  superficial  layers  of  the  mucosa  and  the  skin,  rarely  extending  suf- 
ficiently deep  to  justify  their  being  considered  ulcerative.  During  this 
stage,  usually  at  its  beginning,  there  is  commonly  malaise  and  slight 
fever  (syphilitic  fever).     The  intensity  of  the  infectious  processes  may 


UACTKkIA    AS   CAUSKS   OF   DISKASE.  1  ;<; 

be  further  iiulicated  by  the  occurrence  of  inHammation  of  the  ins  or 
retina,  joint  and  bone  pains,  splenic  and  lieinitic  enlarj^cments,  and 
alopecia. 

A  most  conspicuous  lesion  of  this  sta^e  is  the  so-callcfl  mu- 
cous patch.  This  ai)pears  on  the  mucosa  of  tlie  mouth,  on  the  j^'cnital 
mucous  membranes,  and  upon  the  anal  mucosa;  a  similar,  if  not  iden- 
tical, lesion  is  seen  on  the  skin  near  the  anus.  A  typical  mucous  patch 
rarely  attains  a  maximum  diameter  of  i  cm.  and  is  sometimes  covered 
by  a  bluish -white  membrane,  in  which  case  it  is  called  an  opaline  patch. 
These  patches  result  from  superficial  necrosis  and  exfoliation  of  the 
epidermis  involving  part  of  the  Malpighian  layer,  with  degenerative  and 
proliferative  changes  in  the  latter;  there  is  also  more  or  less  infiltration 
of  the  underlying  connective  tissue.  The  round-cell  elements  ];resent 
in  the  base  of  the  ulcer  are  never  so  abundant  as  in  the  initial  sore; 
the  resemblance,  however,  is  striking,  and  the  essentially  infectious  nature 
of  the  lesion  is  further  indicated  by  the  fact  that  the  disease  may  be 
as  readily  communicated  by  the  discharges  from  such  surfaces  as  from 
the  initial  lesion.  The  spirochieta  described  by  Schaudinn  and  Hoff- 
mann is  present  in  the  primarily  enlarged  lymph-nodes,  the  general 
lymphatic  enlargements,  and  in  the  mucous  patches.  F"emales  transmit 
syphilis  more  frequently  by  the  last  named  lesions  affecting  the  vulva 
and  vagina  than  by  the  chancre,  and  syphilis  of  the  innocent  is 
usually  the  result  of  contact,  immediate  or  mediate,  with  the  highly 
infective  discharges  to  which  it  gives  rise.  Instruments,  soiled  linen, 
dressings,  drinking  cups,  knives,  forks,  and  spoons  may  be  carriers  of 
the  poison,  which  has  also  been  transmitted  by  the  tattooing  needle 
and  communion  cup  and  by  kissing. 

The  tertiarv  lesions,  which  are  pathognomonic,  are  the  gummata, 
syphilomata,  or  granulation  tumors  of  syphilis.  Gummata  are  develojjcd 
as  masses  of  embryonic  cells,  containing  lymphoid  and  epithelioid  cells, 
with  a  very  slight  amount  of  tral)eculai;  occasionally,  giant  cells  are 
present;  coagulation  necrosis,  hyaline  degeneration,  and  fatty  change 
mav  cause  the  center  to  resemble  caseous  material.  Rarely  a  true 
caseation,  indistinguishable  from  that  seen  in  tuberculosis,  occurs.  The 
retrograde  changes  attacking  gummata  are  necroses  rather  than  de- 
generations, and  are  probably  due  to  the  syphilitic  poison  and  not  to  the 
obliterative  processes  affecting  the  native  and  newly  formed  vessels 
in  the  growth;  both  the  vascular  alterations  and  the  necrosis  are  due 
to  the  same  cause.  Occasionally  secondary  infection  may  give  rise 
to  suppuration.  When  superficially  situated,  necrosis  of  the  overlying 
tissue — skin  or  mucous  membrane^leads  to  infection  and  suppuration. 
With  destruction  of  the  overlying  tissue  there  commonly  appears  a 
central  necrotic  core,  which  separates  slowly.  In  the  absence  of  treat- 
ment the  necrosis  (ulceration;  extends  i»eripherally,  and  in  .some  in- 
stances in  depth  as  well.  At  the  present  time  necrosis  and  ulceration 
are  rare  in  recognized  gummata.  Granulation  tumors  of  syphilitic 
origin  vary  in  size  from  purely  microscopic  bodies  to  masses  five,  ten. 
or  even  fifteen  centimeters  in  diameter,  the  latter  commonly  resulting 
from  confluence  of  smaller  primary  gummatous  areas.  At  first  the 
gumma  is  hard;  later,  with  beginning  degeneration  in  the  newly  for'  ' 
elements — or  more  frequently  as  the  result  of  necrosis — it  bee 
sufficiently  soft  to  resemble  a  cold  abscess  or  to  manifest  pseudofluctua- 
tion  and  be  mistaken  for  a  cvst. 


l8o  GENERAL  PATHOLOGY. 

Gummata  are  sometimes  multiple,  occurring  simultaneously  in  a 
number  of  the  tissues  and  organs.  A  single  nodule  is,  however,  the  rule. 
Syphilomata  may  occur  in  nearly  all  the  tissues,  but  are  most  fre- 
quently observed  in  connection  with  the  periosteum,  particularly  that 
of  the  cranial  bones.  Frequently,  they  are  situated  in  the  subcutaneous 
tissue;  they  also  occur  in  the  liver,  kidney,  and  lung,  and  even  in  the 
heart.  The  brain  is  not  infrequently  affected.  In  the  mucous  mem- 
branes— particularly  of  the  larynx,  trachea,  nose,  and  pharynx — and  in 
the  rectum  extensive  tissue  destruction  may  result.  With  ulceration,  or 
even  in  its  absence,  the  subsequent  cicatrization  may  give  rise  to  nar- 
rowing of  those  tubes  the  walls  of  which  are  involved.  Such  strictures 
are  seen  in  the  rectum  and  in  the  trachea. 

Parasyphilitic  manifestations  follow  syphilis,  but  have  little  or  no 
morphologic  resemblance  to  the  frank  changes  which  it  induces.  For 
the  term  parasyphilis^  and  its  derivatives  Fournier,  the  eminent  French 
syphilographer,  is  responsible.  Ogilvie  happily  defines  a  parasyphilitic 
affection  as  syphilitic  in  origin  but  not  in  nature.  There  is  some  want 
of  distinction  between  the  really  syphilitic  and  parasyphilitic  affections. 
The  diseases  of  the  nervous  system  following  syphilis  (for  example, 
dementia  and  tabes  in  acquired  syphilis,  and  mental  defect  and  internal 
hydrocephalus  in  the  congenital  form)  develop  none  of  the  histologic 
changes  seen  in  the  familiar  lesions  of  syphilis;  that  they  may  follow 
and  be  due  to  syphilis,  there  can  be  no  doubt. 

'  Foumier's  monograph  is  in  French.  Post,  "Boston  Med.  and  Surg. 
Jour.,"  Oct.  15,  1903,  summarizes  this  subject;  see  also  Ogilvie,  "Lancet," 
June  13,  1903,  p.  1647. 


CllAl'TI-.R   \  1. 
ANIMAL  PARASITES  AS  CAUSES  OF  DISEASE. 

The  animal  parasites  tliat  occur  in  man  may  l>e  ct^nsidered  in  three 
general  groups:  (I)  Protozoa,  (II)  Vermes,  (111)  Arthropoda.  It  is 
not  within  the  scope  of  this  work  to  deal  with  the  general  zoology  of 
parasites  or  to  consider  them  exactly  in  their  zoologic  order.  For 
special  consideration  of  these  facts  the  reader  is  referred  to  standard 
treatises   on   the   subject.* 

Amebiasis  is  a  term  proposed  by  Musgrave  and  Clegg  for  diseases 
due  to  amebas.-  Amebas  are  protozoa^  belonging  to  the  rhizopoda. 
Forms  not  known  to  be  pathogenic  have  been  found  in  the  mouth,  feces, 
vaginal  discharges,  and  in  the  urine.  The  relation  of  the  Amoeba  gingi- 
valis  and  the  Ama-ba  buccalis  to  disease  processes  remains  undetermined. 
The  most  important  members  of  this  group  are  those  found  in  the  intes- 
tine, called  bv  Schaudinn  entameba,  of  which  he  recognizes  two  forms, 
(i)  The  Entamoeba  coli  he  regards  as  a  normal  inhabitant  of  the  upper 
portion  of  the  colon  and  present  in  the  stools  whenever  any  diarrheal 
process  hastens  evacuation  of  the  intestinal  contents.  (2)  This,  the 
second  form,  he  calls  the  Entamoeba  histolytica,  or,  from  the  disease 
with  which  it  is  quite  commonly  associated,  the  Entamoeba  dysenteric. 
He  shows  by  certain  peculiarities  in  its  encystment  and  repro<luctive 
phenomena  that  it  diflers  materially  from  non-jiathogenic  amebas. 
The  Entamoeba  histolvticais  12  ,".  to  35  ,"or  40  ,"  in  diameter,  and  while 
living  and  fullv  developed  actively  motile.  The  nucleus  when  demonstra- 
ble is  round  or  ovoid,  the  protoplasm  granular  and  often  vacuolated;  the 
phagocvtic  power  of  the  parasite  is  shown  by  the  frequency  with  which 
its  ]jrotoplasm  contains  red  blood-cells,  leukocytes,  bacteria,  and  granu- 
lar detritus.  Pure  cultures  of  the  ameba  have  not  been  obtained ;  they 
mav,  however,  as  shown  by  Musgrave  and  Clegg,  be  grown  in  symbiosis 
with  bacteria. 

Demonstration. — For  the  technic  of  cultivation  the  reader  is  re- 
ferred to  the  monograph  by  Musgrave  and  Clegg.  A  satisfactory 
recognition  of  the  parasite,  particulariy  in  the  hands  of  the  novice,  de- 
mands that  he  should  see  it  send  out  pseudopodia ;  he  should  observe 
active  movement.  In  order  to  do  this,  the  material  should  he 
reasonablv  fresh.  In  the  case  of  feces,  admixture  with  unne  is 
to  be  avoided.     A  drop  of  the  suspected  material  is  placed  upon  a 

•Braun,  '•  Parasitcn  dcs  Mcnchen,"  190.?  AKso  Doflcin.  "  Protozfxn  als 
Parasiten  u.  Krankhcitscrreecr."     Zweite  AuflaRC,  Jena,  iQo.v 

»See  papers  bv  Harri.s,  and  bv  Futchcr,  "Jour.  Amer.  Med.  Assoc  Auk- 
22  1Q02.  Craig,  ''Amer.  Med.,"  feb.  20,  IQ04.  Schaudinn,  "Arb.  a.  d.  Kais. 
Ge'sundheitsammte,"  Bd.  xix  and  xx.  Musgrave  and  CIcrr  Bulletin  No.  18. 
Bureau  of  Government  Laboratories,  1904.  Calkins.  "Arch.  f.  Protistenk..  1904. 
p.  1.     Castellani,  "Centralbl.  f.  Bakt.,"  Jan.  as,  1905.  P-  66. 

'Calkins,    "The   Protozoa."    looi.     Clarkr        P- "-.   and   Disea^.       ,oa, 

Doflcin,  reference  given  above. 

181 


I 82  GENERAL  PATHOLOGY. 

slide  and  a  cover-glass  applied.  The  slide  may  be  gently  warmed,  or 
the  microscope  may  be  kept  in  a  reasonably  warm  place,  under  which 
conditions  movement  will  be  more  active.  Fresh  specimens  may  be 
best  stained  by  mixing  with  the  suspected  material,  placed  upon  a  slide, 
a  drop  of  a  watery  solution  of  toluidin  blue.  This  reagent  acts  as  a 
fixative  and  at  the  same  time  stains  the  amebas  intensely  and  rapidly. 
Pieces  of  tissue  are  best  fixed  in  corrosive  sublimate,  embedded  in  paraf- 
fin, and  the  sections  stained  in  eosin,  followed  by  toluidin  blue  for 
twenty  or  thirty  minutes;  wash  and  differentiate  in  alcohol,  clear  in 
cedar  oil  or  xylol,  mount  in  balsam.^  For  the  demonstration  of  amebas 
in  tissue  or  pus  Mallory^  recommends  the  following  method,  which  does 
not  yield  satisfactory  results  when  the  parasites  are  in  feces:  (i)  Fix 
in  alcohol;  (2)  section  by  celloidin  or  paraffin  method,  preferably  the 
latter;  (3)  stain  sections  in  a  saturated  aqueous  solution  of  thionin 
three  to  five  minutes;  (4)  wash  in  water;  (5)  differentiate  in  2  per  cent, 
aqueous  solution  of  oxalic  acid  one-half  to  one  minute;  (6)  w^ash  in 
water;  (7)  dehydrate  (celloidin  sections  95  per  cent,  alcohol,  paraffin 
sections  absolute  alcohol);  (8)  clear  (celloidin  sections  in  oleum  origani 
cretici  or  oil  of  bergamot,  paraffin  sections  go  direct  to  xylol);  (9)  wash 
in  xylol;  (10)  balsam.  The  nuclei  of  amebas  and  granules  of  mast  cells 
are  brownish-red,  other  nuclei  are  blue. 

Pathogenesis, — The  morbid  anatomy  of  amebic  dysentery  and  its 
complications  will  be  considered  in  Part  III  of  this  l30ok,  in  chapter 
dealing  with  Diseases  of  the  Alimentary  Canal;  amebic  abscess  is  de- 
scribed with  abscesses  of  the  liver.  Of  the  other  amebas  associated  with 
suppurative  and  inflammatory  processes  we  possess  no  accurate  infor- 
mation establishing  their  disease-producing  function.  With  this  group 
should  be  classed  the  ameba  found  in  serous  exudates  and  in  abscesses 
about  the  mouth,  and  the  ameboid  organisms  which  have  been  encount- 
ered in  the  urine.  The  ameba  described  by  Behla  in  the  sputum  of  pertus- 
sis has  not  been  established  as  holding  any  causal  relation  to  the  disease. 

Among  the  flagellated  mastigophora  are  a  number  of  parasites  occa- 
sionally found  in  man;  several  of  these  have  been  grouped  under  the 
name  Cercomonas  hominis.  Systematic  writers  have  incorrectly  in- 
cluded with  this  group  parasites  possessing  more  than  one  flagellum. 
True  cercomonads  are  pear-shaped,  8  />.  to  12  !>.  long,  and  possess  a  single 
flagellum  at  the  anterior  end.  They  are  not  uncommonly  found  in 
stools  and  probably  have  no  important  pathogenic  property.  The 
trichomonas  group  includes  several  closely  allied  parasites.  The 
Trichomonas  intestinalis  is  10  ,".  to  12  ,".  long,  pear-shaped,  spiculated 
at  one  end,  ciliated  along  a  part  of  one  margin,  and  may  have  three 
or  four  flagella.  A  similar  organism  is  sometimes  observed  in  vaginal 
discharges  and  is  called  the  Trichomonas  vaginalis. 

The  Balantidium  coli^  is  a  protozoal  parasite,  but  belonging  to  a 
family  differing  from  the  cercomonas;   it  has  been  shown  to  be  capable 

^  See  remarks  on  the  use  of  anilin  dyes,  p.  49. 

^"Jour.  Exper.  Med.,"  vol.  ii,   1897,  p.  529. 

^Solovieflf,  "  Russki  Vratch,"  vol.  i,  No.  14.  Brooks,  "X.  Y.  Univ.  Bull, 
of  the  Med.  Sci.,"  vol.  ii,  Jan.,  1902.  Strong  and  Musgrave,  "Bulletin  Johns 
Hopkins  Hospital,"  Feb.,  1901.  Solojew,  "Centralbl.  f.  Bakt.,"  Abt.  I,  1901, 
xxix,  821-831,  849-860.  Klimenko,  "Ziegler's  Beitrage,"  1903,  Bd.  2,7,,  p.  281. 
Janowski,  "Zeit.  if.  klin.  Med.,"  Bd.  32,  p.  415.  Ehmrooth,  "Zeit.  f.  klin.  Med.," 
Bd.  xlix,  p.  321. 


ANIMAL   PAKASITKS   AS  CAUSES  1)1"   DISKASI 


'83 


of  producing  disease  in  man.  The  orj,'anism  is  ovuidal,  sligluly 
broader  at  the  anterior  end,  and  measures  50,"  to  100,"  in  lenj,'th  anil 
40  n  to  60  ."  in  hreadlli.  A  funnel-shaped  o])eninj^^  (peristome)  is  situ- 
ated in  the  anterior  cntl;  the  macronuclcus  is  reniform  and  the  micro- 
nucleus  globular.  The  motility  of  the  parasite  depends  upon  the 
activity  of  the  long  cilia  that  cover  it.  About  100  cases  of  diarrhea  or 
dysentery  believed  to  be  due  to  the  balantidium  have  been  recorded. 
That  the  parasite  may  enter  the  mucosa,  and  even  the  muscuiaris,  of 
the  intestine,  has  been  abundantly  shown.  Necrotic  foci,  hemorrhagic 
areas,  and  irregular  ulcers  are  found  in  the  colon.  The  parasite  has  been 
observed  in  the  lymphatics  of  the  intestinal  wall  and  in  the  pus  from 
an  hepatic  abscess. 

Most  of  the  trypanosomiases  are  diseases  of  lower  animals,  but  one 
occurs  in  man;    all  are  due  to  organisms  of  the  trypanosomida  group.' 
The  Trypanosoma  Icivisi  is  quite  common  in  rats,  often  without  producing 
any   symptoms.      Nagana, 
surra,    mal    de    caderas, 
and    dourine    are    affec- 
tions usually  occurring  in 
the  horse  and  due  to  the 
Trypanosoma  brucei,   Try- 
panosoma evansi,   Trypan- 
osoma equimmi,  and    Try- 
panosoma   cquipcrdnm   re- 
spectively.    Galzeikte  is  a 
disease  of   bovines  due  to 
the    Trypa)wsoma    theilcri. 
Trypanosomes    have    also 
been  found  in  birds,   rep- 
tiles, batrachians,  and  fish. 
Human  trypanosomiasis  is 
due    to   the   Trypanosoma 
gambiense,    a    flagellate 
parasite  15  /i  to  30  ,"  long, 
1 . 5  /'.  to    2   ,"    thick  ;    one 
margin  of   the  parasite  is 
outlined  by  an  undulating 
membrane,  along  the   free 
margin    of    which    is    at- 
tached a  flagellum  arising  from  the  centrosome  posteriorly  and  i)rojecting 
as  a  free  lash  from  the  anterior  end  of  the  parasite  (see  Fig.  gg.  p.  184). 
The  disease  is  inoculated  by  a  tsetse-fly — the  Glossina  palpalis— and  has 
been  communicated  to  a  number  of  mammalia.     In  man  the  organism 
appears  to  remain  as  a  blood  parasite  for  a  considerable  length  of  time, 
eventually   entering   the  cerebrospinal   fluid  and  giving  rise  to  a  fatal 
disease  called  sleeping  sickness  (African  lethargy). 

'  Laveran   and    Mcsnil.    'Trypanosomes  et   Trj'panosoniiases."    I' 
An  enormous  amount  of  literature  has  recently  accumulated  cnnav- 
parasites.     The  interested  reader  will  fmd  the  most  important  artic' 
files  of  the  "Jour,  of  Tropical  Med.,"  "Brit.  Med.  Jour.."  The  R' 
ports  of  the  Sleeping  Sickness  Commission.  "Ccntralhl.  f.  Bakt.."  i-  ■     ■  -•  ■ . 
and  xxvi.     Annales  dc  ITnst.  Pasteur."  and  •Bulletin  de  I'lnst.  Pasteur. 


Fig.  qS.—  Trypam'-"ma  i  \  ui-i. 
I_-ivcran  and  Mcsnil  stain,     ij  homo,  im.,  i  in.  oc. 


i84 


GENERAL  PATHOLOGY. 


Morbid  Anatomy. — In  the  earlier  stages  there  may  be  no  noteworthy 
alterations;  neuralgias,  edemas,  skin  eruptions,  enlargement  of  the 
lymph-nodes,  and  emaciation  with  irregular  fever  may  be  present.  After 
the  affection  attacks  the  central  nervous  system  Mott  has  shown  that 
a  meningo-encephalitis  results.  Frequently  terminal  infection  by  a 
streptococcus  (hypnococcus  of  Castellani)  produces  a  definite  meningitis 
found  at  autopsy. 

The  possible  relation  of  these  organisms  to  the  spirochaetae  has  been 
mentioned  on  page  172. 

Coccidiosis  is  a  condition  produced  by  invasion  of  cells — mostly 
epithelium — by  parasites  called  coccidia.  They  are  particularly  prone 
to  infect  the  biliary  passages ;  coccidial  cysts  of  the  liver  are  frequent  in 
some  of  the  lower  animals,  especially  the  rabbit,  and  are  occasionally 
observed  in  man.  Once  within  the  epithelial  cell  the  parasite  increases 
in  size  and  divides  into  a  number  of  small,  crescentic  bodies  grouped 

around  a  central  portion  of  inert, 
residual  protoplasm;  the  cell  so 
dividing  is  called  a  schizont,  the  pro- 
cess is  termed  schizogony,  and  the 
resulting  sporules  are  the  merozoites. 
This  method  of  increase  Doflein  calls 
inidtiplicative  reproduction.  The  ac- 
tively motile  merozoites  enter  new 
epithelial  cells  and  repeat  the  pro- 
cess of  schizogony.  Propagative  re- 
production (Doflein)  occurs  through 
the  evolution  of  sexual  stages,  cer- 
tain of  the  merozoites  being  con- 
verted into  sexuall}'  mature  organ- 
isms, called  gametes.  A  merozoite 
enlarges,  its  protoplasm  becomes 
granular  (macroganietocyte)  and 
finally  maturates,  becoming  the  fe- 
male cell  or  niacrogamete.  The  male 
cell  is  also  developed  from  a 
merozoite;  it  is  smaller  than  the 
female  and  the  protoplasm  is  clearer;  its  nucleus  divides,  the  resulting 
chromatin  masses  collecting  at  the  periphery  and  eventually  passing 
out  as  flagellate  bodies.  The  male  cell  is  called  the  micro gametocyte 
and  the  extruded  motile  flagella  containing  chromatin  particles  are 
micro  gametes.  The  flagellated  microgamete  at  once  seeks  and  enters  a 
receptive  eminence  developed  on  the  surface  of  a  macrogamete,  w^th 
the  nucleus  of  which  it  fuses,  completing  the  act  of  fertilization;  the 
resulting  body  is  called  the  zygote.  This  sexual  reproduction  is 
called  sporogony,  which  proceeds  as  follows:  The  fertilized  cell  {zygote), 
possessed  of  active  movement,  is  called,  during  its  migration,  the 
ookinet;  when  it  comes  to  rest  and  acquires  a  capsule  it  becomes  the 
oocyst,  copula,  or  sporont,  and  is  composed  of  a  central  nuclear  mass 
surrounded  by  protoplasm  and  enclosed  in  a  shell  which,  in  some  coccidia, 
is  extremely  resistant.  By  proliferation  of  the  nucleus  and  separation  of 
the  protoplasm,  four  sporoblasts  are  developed.  Each  sporoblast  ac- 
quires a  protecting  membrane  and  is  now  called  a  sporocyst;  by  segmen- 


FlG.     99. — TkYPANUSOMA       GAMBIENSE       IN       HU- 
MAN Blood. 
From  specimen   prepared    by    Dr.   Jimenez    and 
kindly   presented   to   the  writer. 


AN'IMAL   I'AKASrrHS   AS   CAUSES  OK   DISEASE.  185 

tation  of  its  nucleus  two  sf>orozoih-x  arc  dcvcloi)C(l  in  tlic  sjjorocyst.  The 
latter  l)odies  are  sickle-shaped,  possess  a  relatively  hij^h  (Ic^rcc  of  resist- 
ance, and  constitute  a  resting  stage  in  the  cycle  of  the  parasite.  Ivntering 
a  new  host,  the  capsule  of  the  sporocyst  is  digested  or  ruptures,  the  con- 
tained sporozoites  are  liberated,  and,  if  conditions  are  favorable,  at  once 
attack  the  somatic  cells.'  Zoologists  propose  to  classify  coccidia  accord- 
ing to  the  number  of  sporozoites  contained  in  the  sporocyst  developed  by 
each  particular  organism. 

Probably  the  best  known  of  the  coccidia  is  the  Coccidium-  oviforme,  a 
common  ]Kirasitc  in  the  liver  of  the  rabbit  and  occasionally  causing  coc- 
cidia! cvsts  in  the  human  liver.  Such  cysts  have  the  appearance  of  semi- 
solid or  partlv  caseous  nodtiles  resulting  from  jiroliferative  and  necrotic 
changes  in  the  epithelial  cells  of  the  bile-duct.  The  masses  vary  in  size 
and  are  frequently  encapsulated.  The  oocyst  of  the  Coccidium  oviforme 
is  25  ,".  to  30  ,".  long  and  about  half  as  wide.  The  intracellular  j)osition  of 
the  parasite  in  some  of  its  stages  can  frequently  be  seen  in  scrapings,  frag- 
ments, or  sections  from  such  'cysts.  A  skin 
affection  due  to  a  coccidium  has  been  described. 
The  coccidial  origin  of  tumors  has  been  strongly 
advocated  by  a  number  of  observers:  as  the 
demonstration  seems  to  me  to  be  incomplete,  I 
have  not  incorporated  the  various  views  that 
have  been  advanced."* 

There  are  a  number  of  morbid  conditions  of 
obscure  or  undetermined  etiology  in  some  of 
which  parasites  believed  to  be  protozoa  have 
been  described.  Where  the  evolutionary  cycle 
of  the  parasite  has  not  been  worked  out  it  is 
impossible  to  sav  exactlv  to  wnicn  group  tnc  »orme  mom  thk  Human 

alleged  organism"  belongs.     Since  the  observa-  ^ouU.)^""   '"'^^'"' 

tions  of  Van  der  Loeff,^  Pfeiffer,-^  and  Guarnien"  ..\.  x  200  diameters,  b.  c.  x 
numerous  investigators  have  patiently  continued  soodiamcter*. 

attempts    to    establish    the   parasitic    origin  of 

smallpox.  That  this  disease  is  due  to  a  living  contagion  is  clearly  in- 
dicated bv  its  clinical  and  epidemiologic  characters.  The  evidences 
of  its  protozoan  origin  have  recently  been  urged  by  Councilman  ^ 
and  his  students,  who  have  verified  and  extended  j^revious  obser\'a- 
tions.  The  bodies  believed  to  be  parasites  are  included  in  the  epithelial 
cells,  some  forms  being  found  in  the  protoplasm  and  others  within 
the  nuclei.  Calkins^  believes  that  the  known  data  may  be  so  correlated 
that  the   developmental  cycle  of   the    y)arasite  can,   in    part   at   least, 

•  See  diagram  illustrating  the  cycles  of  the  Plasmodium  malaria-,  p.  188. 

'  Zoologists  have  reccntlv  adopted  the  term  eimena  as  the  correct  muTie  for 
the  coccidium:  I  shall,  however,  adhere  to  the  older  nomenclature.  Tyzzer. 
"Jour,  of  Med.  Research,"  April,   1902. 

'Schuller,  'Centralbl.  f.  Bakt.,"  Dec.  la,  1904.  p.  547- 

*  "Monatsch.  f.  prakt.  Derm.."  1887,  Bd.  iv.  p.  189. 

*  Ibid.,  p.  4^5;. 

•  "Arch,  per'le  Sci.  Med.,"  Tome  x.\vi.  p.  403. 

'  "Jour,  of  Med.  Research,"  Feb..  1Q04.  vol.  xi,  No.  1,  PP-,.«  to  361.  with  full 
bibliography.     Howard  and  Perkins,  "Jour,  of  Med.  Research.     Oct  .  IQ04.     bw- 
ing   "  Jour,  of  Med.  Research."  Nov..  1904.  and  Feb..  1905.     De  »^ortc      Lancet. 
Dec    24    1904,  and  "Practitioner."  Jan.,  1905.     Bosc.  "C.  R.  See.  de  Biol.,     t.  v. 
p    1178   also  "Centralbl.  f.  Bakt.."  Aug.  26,  1904.  P-  630.  and  Sept.  23.  »904.  p.  59- 


l86  GENERAL  PATHOLOGY. 

be  followed.  The  name  Cytoryctes  variolae  has  been  given  to  the 
organism,  and  it  is  thought  that  the  difference  between  vaccinia  and 
variola  depends  upon  modifications  in  the  same  parasite.  Mallory' 
describes  a  protozoa-like  body  found  in  four  cases  of  scarlet  fever. 
Negri  -  has  found  a  parasite  of  an  undetermined  nature  occupying  cer- 
tain ganglion  cells  of  the  central  nervous  system  in  hydrophobia. 
Wright,-'  and  also  Marzinowsky  and  Bogrow,^  have  extended  previous 
knowledge  and  made  additional  observations  on  the  parasitology  of  tropi- 
cal ulcer  and  Oriental  boil.  Tietze^  has  found  a  protozoon  in  a  parotid 
tumor,  and  suggests  that  the  parasite  may  be  the  cause  of  the  obscure  en- 
largement of  the  parotid  gland  in  the  condition  called  Mikuhcz's  disease. 

The  scope  of  this  work  does  not  permit  an  exhaustive  review  of  the 
organisms  to  which  reference  has  been  made  in  the  preceding  paragraph. 
In  some  of  the  diseases  investigations  are  incomplete  and  the  results  not 
corroborated  by  a  sufficient  number  of  observers  to  justify  final  judg- 
ment. 

Probably  the  most  important  of  the  sporozoa  are  the  Haemosporidia, 
which,  as  Doflein  aptly  observes,  are  protozoa  that  have  acquired  a 
parasitic  life  adapted  to  existence  within  the  erythrocytes.  A  number 
of  these  organisms  affect  animals  other  than  man,  giving  rise  to 
the  malaria  of  birds,  fish,  etc. 

The  most  important  of  the  hsemosporidia  is  the  parasite  causing 
human  malaria,  called  the  Hsematozoon  malariae,  Haematomonas 
malariae,  Hsemamoeba  malariae,  but  probably  best  known  as  the  Plas- 
modium malariae.^  During  the  presence  of  the  parasite  in  the  circu- 
lating blood  a  large  part  of  its  existence  is  spent  within  the  red  blood- 
cell.  In  man  multiplicative  reproduction  (see  p.  184)  alone  occurs; 
propagative  reproduction  (see  p.  184),  or  the  sexual  cycle  of  evolu- 
tion, takes  place  in  the  body  of  the  mosquito  (Anopheles).  So  far  as  is 
known,  no  other  gnat  can  serve  as  a  host  for  the  Plasmodium  malaria. 
There  are  three  types  of  parasites  observed  in  the  three  forms  of  human 
malaria ;  the  parasite  of  tertian  fever  completes  its  cycle  of  development 
in  forty-eight  hours,  the  plasmodium  causing  quartan  malaria  requires 
seventy-two  hours  for  the  production  of  sporulation,  and  in  the  so- 
called  estivo-autumnal  or  pernicious  malaria,  the  parasite — Plasmodium 
vivax^varies  in  the  length  of  time  necessary  for  its  complete  evolution. 

The  most  frequent  form  of  malaria  is  that  produced  by  the  tertian 
parasite  (Plate  I),  the  evolution  of  which  may  be  traced  by  repeated 
examinations  of  the  peripheral  blood,  beginning  immediately  after  a 
paroxysm  and  continuing  at  intervals  of  two  to  four  hours  until  the 

'  "Jour,  of  Med.  Research,"  Jan.,  1904,  p.  4S3. 

*  "Zeit.  f.  Hyg.  und  Infektkrank,"  1903,  xliv,  p.  507. 
'  "Jour,  of  Med.  Research,"  1903,  vol.  x,  p.  472. 

*  "Virchow's  Archives,"  1904,  Bd.  178,  p.  112. 

*  "Mittheil.  a.  d.  Grenzgebiet.  de  Med.  u.  Chir.,"  1904,  xiv.  No.  3. 

°  All  the  important  literature  bearing  on  malaria  ma}^  be  traced  from  the 
references  given  by  DaCosta  in  his  "Clinical  Hematolog}^""  second  edition,  1905, 
PP-  445  to  472.  See  also  Doflein,  "  Protozoen  als  Parasiten  u.  Krankheitserreger," 
Zweite  Auflage,  Jena,  1903.  Schaudinn,  "Arbeit,  a.  d.  Kaiser  Gesundheit- 
sammte,"  1902,  Bd.  xix,  and  1903,  Bd.  xx.  Stephens  and  Christophers,  "Prac- 
tical Study  of  Malaria,"  London,  1903.  Nuttall's  exhaustive  studies  on  the 
biology  of  the  Anopheles  will  be  found  in  the  "Jour,  of  Hvgiene,"  1901,  vol.  i, 
and  1902,  vol.  ii.  Craig,  "Amer.  Med.,"  Oct.  29,  1904,  on  "Latent  and  Masked 
Malarial  Infections." 


Pl.ATl:    I. 


■-.*.  -.iV. 


9% 


^        <■•■•;$ 


13 


14 


o 


15/ 


Tmk  Tkktian  Pakasi  j  i 
(From  Pa  Ciista's  "  (."Hiikal  Hriii:a<i|>M;\      > 

t.    .\o>  ma/  I'lylhi  Divlr. 

2.  3.  4-  5-    lnt>  acrllulai  hyaliur  forms. 

6,7.  Yoiiuc:  pii;mfnti'd  iiitracflliilai  Q>> ms.  In  ^)  two  distinct  parasites  inhabit  the  ery- 
throcyie.  tlu-  larger  one  beiiiK  actively  anii'boi<l.  as  i-viili-ni-<.-<l  by  the  loiij"  tentacular 
process  trailing  from  the  main  lurtly  of  ttie  orKanisni.  This  aineboiij  leiulenrv  is 
still  better  illustrated  in  7,  by  the  riblion-like  desiKii  formed  b\  the  p.irasile.  N*<ite 
the  delicacy  of  the  pigment  granules,  and  their  tendency  tovvaril  peripheral  arrange- 
ment in  6,  7.  and  s. 

8.  Latfr  dei-flofimi'iital  slairf  <>/ 7-  In  7,  S,  and  <)  cnlarKement  and  pallor  of  the  infected 
erythrocyte  become  conspicuous. 

q.    Mature  inttaci-tliilar  pii^iiii-nlfd  f>iiiit>ili\ 

10,  II,  12.  Srx>"f)ilintr /"'ws.  In  10  is  shown  the  early  stage  of  s|Kirulation— the  develop- 
ment of  radial  striations  and  peripheral  indentations  coincidentallv  with  the  swarm- 
iiiK  of  the  pigment  toward  the  center  of  the  parasite.  The  completion  <•!  this  procesn 
is  illustrated  by  11  and  IJ. 

13.  Large  ixcnlli')!  i-xtraicllular  form.  Note  the  coarse  fused  blocks  of  piL;meiil.  (fom- 
pare  size  with  that  of  normal  erythrocyte,  l.i 

\\.    Flagellale form. 

15.  Sill  unki'ii  atnifi  agmenting  fxli  act-llnlarfoi ms. 

16.  yacuoliilion  of  an  f  rfi  accUii/ar  for  m. 

Note.— The  original  water-color  drawings  were  made  from  fresh  blood  tnccimens.  a 
Leitz  t'2-inch  oil-immersion  objective  and  4  ocular,  with  a  Zeiss  camcra-lucida,  being  usc«i. 

(E.  F.  Fabkr. />«-.) 


AN'IMAL   PARASITES   AS  CAUSES  OF   DISK  AS  K.  I  ft; 

cycle  is  completed.     If  u  drop  of  tlic  fresh  blood  be  prejiarcd  for  ex- 
amination  (see  Technic  of   Blood   Examination,  Chapter   I.   Part   III) 
during  or  immediately  after  the  paroxysm,  the  earliest  sta^'es  in  the 
evolntion  of  the  plasmodium  may  readily  be  followed.     A  magnifiration 
of    about    looo  diameters   (,'.v-inch  oil    immersion)   will  be  found  con- 
venient, but  not  absolutely  necessary,  as  the  discoverer  of  the  para.site, 
Laveran,  commended   a  magnification  of  600   (,\-inch  or  J -inch   objec- 
tive, with  a  good  eye-piece).    Carefully  focusing  on  a  part  of  the  held 
in  which  the  red  blood-cells  are  thinly  spread,  the  slide  is  slowly  moved, 
a  close  watcli   being  kept   for  pale  bodies  in  the  corpuscles,  or  for  pale 
corpuscles,  in  which  the  parasite  is  to  be  sought.     The  iris  diaphragm 
with  substage  condenser  should  l)e  partly  closed,  so  as  not  to  flood  the 
field  with  light  sufticient  to  obliterate  the  finer  details.     In  varying 
numbers  of  the  red  blood-cells  transparent  (hyaline)  bodies  with  fairly 
sharp  margins  can  readily  be  found.     The  smallest  of  these  does  not 
exceed  2  ,".  in  diameter,  and  if  carefully  watched  its  form  will  be  seen 
constantly  changing.     In  the  earliest  stage  it  is  without  pigment  and 
resembles  the  so-called  vacuole  or  hydropic  spots  sometimes  seen  in 
erythrocytes,  from  which,  however,  it  is  readily  differentiated  by  the 
rapid  ameboid  movements  of  the  plasmodium.     In  another  specimen 
of  blood  collected  three  or  four  hours  later  the  intracellular  parasites 
will  be  found  very  much  larger,  the  ameboid  movement  more  active, 
the  pseudopodia  appearing  and  disappearing  constantly.     Sometimes 
the  protoplasmic  projections,  thrust  through  the  interior  of  the  red  cell, 
meet,  imprisoning  part  of  the  hemoglobin  content  in  the  interior  of  the 
parasite.     To%vard  the  end  of  the  first  twenty-four  hours  following  a 
paroxysm,  pigment  begins  to  appear  in  the  interior  of  the  parasite  and 
the  Plasmodium  becomes  proportionately  easier  to  recognize.     This  pig- 
ment is  composed  of  fine  brownish-yellow  granules,  most  abundant  near 
the  periphery  of  the  organism  and  in  constant  motion.     If   the  slide 
be  cooled,  the  vibrations  of  the  pigment  become  slower  and  eventually 
cease.     Bv  this  time  the  parasite  occupies  about  half  of  the  erythrocyte. 
During  the  evolution  of   the  plasmodium  the  affected  red  cell  becomes 
slightly  swollen  and  progressively  paler.     In  from  four  to  six  hours  before 
the  approaching  paroxysm,  the  parasite  has  attained  its  maximum  size 
and  the  process  of   sporulation  begins.     The   pigment   granules  collect 
toward  the  center,  the  periphery  of  the  parasite  is  outlined  by  numer- 
ous short  arcs  the  convexity  of  which  is  towanl  the  periphery  of  the 
er>'throcytes,  and  from  the  points  where  these  arcs  meet,  faint  lines  are 
projected  toward  the  centrally  collected  mass  of  jiigment.     As  this  stage 
is  completed  the  parasite  is  divided  into  fifteen  or  twenty  oval  or  pyn- 
form  segments,  the   apices  of   which  are  directed  toward  the  inactive 
pigment  in  the  center.     As  now  seen,  the  remains  of  the  swollen  eryth- 
rocyte are  indistinct  and  the  radiating  spores  present  the  characteristic 
rosette  or  daisv  form.     With  the  completion  of  sporulation  the  red  cells 
containing  the  parasites  rupture,  the  liberated  young  plasmodia  are  freed 
in  the  blood-plasma  and  at  once  enter  red  cells.     The  liberated  pigment 
is  taken  up  by  the  phagocytes,  particularly  the  leukocytes,  but  also  by 
phagoc^-tic  endothelial  cells.  . 

A  careful  examination  of  the  blood  will  show  that  in  a  numl^r  of 
the  infected  red  cells  sporulation  does  not  occur,  and  that  in  an  earlier 
stage  in  the  evolution  of  the  parasite  it  escapes  from  the  host  cell.      I  his 


GENERAL  PATHOLOGY. 


12  A  B 


Fig.  ioi. — Diagrammatic  Representation  of  the  Life  Cycle  of  the  Plasmodium    malari.e. — (Modified 

and  redrawn  ajter  Clarke.) 
[The  letters  refer  to  the  stages  of  schizogony  and  the  figures  to  sporogony.] 

A.  Hyaline  intracorpuscular  body  called  by  Lankaster  the  amebula,  the  earUest  stage  of  the  parasite  \\-ithin  the  red 

cell. 

B.  Later  stage  of  A,  showing  beginning  formation  of  pigment.     A  and  B  are  stages  in  the  growth  of  the  merozoite, 

and  with  C  constitute  the  changes  in  the  schizont  during  the  process  of  schizogony. 

C.  Sporulating  intracellular  parasite;   daisy  or  rosette  form;   pigment  in  center. 

D.  Ruptured  cell  hberating  sporules  or  merozoites,some  of  which  return  to  red  cells,  as  indicated  bv  the  arrow,  and 

repeat  this  process  of  schizogony  or  multipUcadve  reproduction.     Other  merozoites  after  intermediary  stages 
develop  into  gametes. 

1.  Microgametocyte  or  male  element. 

2.  Macrogametocyte  or  female  element. 

3.  IMicrogametocyte  from  which  two  microgametes  are  being  given  off  (exiiagellation) ;  one  microgamete  has 

separated.     The  dots  in  the  microgamete  imperfectly  represent  contained  particles  of  chromatin. 

4.  Macrogamete  which  has  just  completed  maturation  by  e.xtruding  part  of  its  nuclear  substance  represented  by 

the  dots  above  the  cell. 

5.  Fertilization  of  the  macrogamete  by  the  entrance  of  the  microgamete  through  the  receptive  eminence.     This 

body  is  now  a  zygote. 

6.  Motile  body  developed  from  the  zygote  and  called  the  ookinet,  which,  as  indicated  in  the  diagram,  is  about 

to  penetrate  the  walls  of  the  mid-intestine  of  the  mosquito. 

7.  Epithelium  of  mid-intestine  of  mosquito. 

8.  Oocyst  in  the  wall  of  the  gnat's  intestine;   nuclear  diWsion  has  occurred. 

9.  Matured  oocyst,  or  sporocyst,  which  has  ruptured,  permitting  the  sporozoites  to  escape  into  the  body-cavity  of 

the  mosquito,  from  which  they  pass  to  the  sahvary  gland  of  the  insect. 

10.  Part  of  veneno-sahvary  gland  of  the  mosquito;   numerous  sporozoites  are  present  in  the  cells  of  the  gland  and 

in  the  duct  to  which  the  pointer  leads. 

11.  Sporozoite  escaping  from  the  gland  duct. 

12.  Free  sporozoite  ready  to  enter  the  erythrocyte  of  a  new  host. 


HLATI     II. 


2  3  4  5  6 


7  8  9  10  11 


•:^  t  ...  '  :   ■     I 


The  Qlartan  Parasitk. 
(Frum  D.i  Costa's  "  Cliiiiial  Hematology.") 


I.    Xormal  riylhi  ocvlr. 

j!   '"i\m!^^plglL-lu'd"int"^^^^^^  Note  ilic  coarseness,  dark  color,  ami  scanliiio.- 

4   s  6  7''^!fl/i'r,/,!",7lv>«!.v?/"/'^vV,;x-,-.v  o/.f.     Note  the  peripheral  distrihutioii  of  the  plRmcm 

In  all  the  parasites  frum  y  to  8.     (Compare  si/e  and  color  of  the  erythroc>tC5  in  j.  6. 

and  7  with  7. 8.  and  o.  Plate  I.)  ,     .  ,  .  ,  _ 

8.   .l/d/w'r    intiackluhii    t\»»t.      Note  that    the  stroma  of    the  erylhrcKyte  is   no  longer 

demonstrable.                                                  .        .                              i-   ..        !•  t  .  ■ 

q.  ID,  II.   Se^meulmy:  fo,ms.     In  o  are  shown  the  cliaractenstic  radiating  lio f  ..uM.wnt 

(Compare  with  lo.  it,  and  12,  Plate  I,  and  with  .0.  n.  a<"l  U.  »'late  III 
la.    Large  swolhit  iilrac-llular  form.    (Compare  with  13,  Plate  I.) 

13.  HaKfllatf  /oiiii.     (Compare  with  14.  Plate  I.) 

14.  I'ticiiolalioii  0/  an  exti  acellular  fni  m. 


ANIMAL   PARASITES   AS   CAUSES   OF  DISEASE.  I  89 

step  is  ihc  tirst  sta<];e  in  tlie  evolution  of  the  sexual  life  of  the  Plas- 
modium, antl  it  is  now  prepared  to  enter  the  tissues  of  another  host. 
Certain  of  these  e.xtraccllular  pij^mented  forms  (gametes)  are  macro- 
gametocvtes  and  others  microgametocytes,  the  later  evolution  of  which 
occurs  in  drawn  blood  only.  A  mosquito  of  the  genus  Anopheles  is 
the  host  in  which  the  sul)sequent  development  of  the  parasite  occurs. 
When  the  blood  enters  the  stomach  of  the  mosquito,  the  microgametes 
thrown  of?  from  the  microgametocytes  enter  and  fecundate  the  macro- 
gametes,  which  become  ookinets.  These  bodies,  endowed  with  motility, 
penetrate  the  mucosa  of  the  mid-intestine  of  the  gnat  and  become 
oocysts  in  the  intestinal  wall.  By  changes  already  described  (see  p.  184) 
the  oocvst  develops  into  a  sporocyst  and  ruptures  into  the  body  cavity 
(coelom)  of  the  mosquito ;  the  liberated  sporozoites  eventually  reach  the 
salivary  gland  of  the  gnat  and  enter  the  venom  duct,  from  which,  when 
the  insect  next  feeds,  they  are  inoculated  into  the  human  host.  The 
formation  of  flagellate  bodies  does  not  occur  in  the  circulating  blood, 
but  in  properly  prepared  mounts,  made  just  before  the  malarial  par- 
oxysm, the  formation  of  flagella  may  be  seen  between  fifteen  and  thirty 
minutes  after  the  blood  is  drawn.  The  pigment  of  the  macrogametocyte 
becomes  actively  disturbed,  and  from  the  periphery  of  the  plasmodium 
pointed  or  bulbous  flagella.  often  20  .".  to  30  ,".  in  length,  are  thrust 
violently  into  the  surrounding  plasma  and  may  often  be  seen  lashing 
contiguous  cells;  a  flagellum  loosened  from  the  microgametocyte  may 
sometimes  be  seen  free  among  the  red  cells.  In  properly  stained  speci- 
mens each  flagellum  is  found  to  contain  more  or  less  chromatin,  either 
collected  in  the  bulbous  extremity  or  distributed  along  the  center  of 
the  filament. 

The  development  of  the  quartan  parasite  follows  closely  that  already 
outlined  as  occurring  in  the  tertian,  l)ut  shows  sufficiently  distinctive 
characters  to  enable  the  observer  to  differentiate  the  two  organisms. 
The  hvahne  intracellular  form,  in  its  early  stage,  is  indistinguishable 
from  that  of  the  tertian  parasite.  By  the  time  pigmentation  has  ap- 
peared certain  differentiating  points  may  be  recognized.  The  pig- 
ment is  coarser,  darker,  and  sluggish;  the  outlines  of  the  parasite  are 
sharper,  and  as  it  grows  older  its  movement  becomes  less  active.  The 
infected  red  cell  shrinks  and  grows  darker,  occasionally  taking  on  the 
so-called  "brassv"  hue.  The  protoplasm  of  the  parasite  appears  denser 
and  more  gravish  than  that  of  the  tertian  fomi.  The  tertian  parasite 
produces  sixteen  to  twentv-four  segments,  the  quartan  eight  to  twelve. 
The  former  requires  fortv-eight  hours  and  the  latter  seventy-two  hours 
for  com])leting  the  hem'al  cycle.  The  asexual  cycle  of  the  quartan 
parasite  follows  in  essential  detail  that  outlined  for  the  tertian. 

The  estivo-autumnal  parasite  Plasmodium  vivax  -varies  in  the 
length  of  time  neccs.sary  for  its  developmental  cycle.  While  all  stages  in 
the  evolution  of  the  quartan  parasite  may  readily  l)e  obtained  in  the  per- 
ipheral blood,  sporulating  forms  of  the  estivo-autumnal  organism  arc  never 
present  peripherallv.  In  the  earlier  stages  the  intracellular  hyaline  body 
is  not  unlike  similar  forms  seen  in  tertian  and  quartan  parasites.  Soon, 
however,  ameboid  rings  or  signet-ring  shapes  are  found,  and  rapid  changes 
from  the  ring  to  a  tlattened  disc  are  regarded  as  characteristic  of  this  or- 
ganism. The  pigment  is  fine  and  never  almndant.  Segmentation  may  lie 
seen  in  the  splenic  blood  drawn  during  life,  or  in  the  marrow  postmortem. 


igo 


GENERAL  PATHOLOGY. 


The  segmenting  forms  are  smaller  than  in  the  other  plasmodia,  although 
following  in  a  general  way  the  rosette  shape  of  the  tertian  parasite.  After 
a  week  or  ten  days  the  most  characteristic  evidence  of  estivo-autumnal 
infection  Ijecomes  demonstrable  by  the  appearance  in  the  peripheral  cir- 
culation of  crescent,  round,  and  ovoid  bodies  usually  contained  in  the  thin 
shell  of  the  now  colorless  erythrocyte.  These  crescents  resemble  a  moon 
in  the  first  quarter  with  the  points  of  the  horns  slightly  rounded,  and 
measure  5  ,"  to  8  ,"•  in  length.  The  pigment  is  usually  centrally  placed. 
The  ovoid  forms  are  commonly  smaller  than  the  crescents  and  part  of  the 
host  cell  can  nearly  always  be  shown  about  them.  It  is  evident  that 
these  structures  are  gametes.  In  the  proper  condition  the  formation  of 
fiagella  may  readily  be  recognized. 

TABULATED  DATA   USEFUL  IN   DIFFERENTIATING  THE    PARASITES 

FOUND  IN  MALARIA. 


Tertian  Parasite. 


Hyaline   body, . 


Pigment  granules, 


Outline  indistinct; 
actively  ameboid. 


Fine,  light-brown, 
active. 


Size     of     mature 

parasite, As  large  or  larger 

than  erythrocyte, 
■J  fi  to  g  fi. 


Quartan  Parasite.        I  Estivo-autumnal  Parasite. 


Outline  distinct ; 
ameboid  m  o  v  e  - 
ment  slow. 


Small,  sharply  out- 
lined, active;  ring- 
shape,  common. 


Coarse,  dark-brown, 
sluggish,  peripher- 
ally  placed. 


Smaller    than    ery- 
throcyte, 5  /i  to  6  /i. 


Sporulation     se^ 
ments, 


Very  fine , 
motile  or 
ary. 


scanty, 
station- 


Usually  very  much 
smaller  than  ery- 
throcyte, 2  /i  to  6  ,u. 


15  to  24.     Usually  ,6  to   12.     Arranged  ;  6    to     15     or    more. 


m  two  rows  or 
irregularly 
placed. 


Pre  f  1  a  ge  Hate 

form, ISwollen,   pig- 

I     mented  body  9  fi 
I     to  12  /i  in  diam- 
eter. 


symmetrically  Symmetrically 
around  central  j  or  irregularly 
pigment.  1     placed. 


Swollen,  p  i  g  - 
mented  body,  5  p. 
to  8  /i  in  diam- 
eter. 


Erythrocyte, 


Becomes  pale  and 
greatly   swollen. 


Becomes  dark  in 
color  and  shrunk- 
en. 


Spherical,  pig- 
mented body,  4  jj. 
to  6  /I  in  diam- 
eter. 

(Derived  from  cres- 
cents.) 


Greenish    or    ' '  bras- 
sy" in  color. 
Often   crenated. 


Cycle, . 


48  hours. 

Sporulating  forms 
not  abundant  in 
peripheral 
blood. 


72  hours. 

Sporulating  forms 
fairly  nvimerous  in 
peripheral 
blood. 


24   or   48   hours. 

Sporulating  forms 
in  spleen  and  bone- 
marrow. 


i'lvri    III. 


•?         -rr 


10  11 

12  13 


19  ^^  21  22 

15  16  17  18 


26 


ThK    ESTIVO-Al'TlMs  \i     1'xk\-,1ii 

(From  Da  Costa's  "  Clinical  HcmatoJogN.") 

1.  .\'i»iiial  f'l  villi  iicvli-. 

2,  3-    y'oitiijf  hyaliiif  i  ing-t'ot ms. 

4,5,6.    Inliacellulai  lixiiliiif  /onus.     In  4  the  jKirasitc  appiMni  as  an  IrrrKUlarh  shaped  disc 
with  a  thiniicd-oiit  central  area.     In  5  and  6  its  ameboid  properties  arc  ODvious. 

7.  Yoiint:  piemriiird  iiitiacrllular  form.      Note  the  extreme  delicacy  and  small  immhcr  o( 

the  pi.ijmeiit  Rratinles.     (Compare  with  6.  J'lale  I,  and  with  .;.  Plate  II.) 

8,  9.    l.alfi  dt-vrliifiiiifntal  stagfs  of  7. 
10,  II,  12.    Sfgrnenliiig  forms. 

13.  14.    CrfSCfntic  forms  at  early  stages  of  Iheii   deveiapmeiit. 

15,  16,  17,  18.  10.    Ctrscentic  forms.    In  i.s  and  !■)  a  distinct  "  bib  "  of  the  crMhrocMc  is  visible. 
N'acuolation  of  a  crescent  is  shown  in  iS,  aiul  jxilar  arranfcement  v\  the  piKmeni  in  17. 

20.  (yval foim. 

21.  22.   .Sphetical  forms. 

23.  Flagellate  fotm. 

24.  I'aciiolation  and  deformity  of  a  spherical  fotm. 

2,s.    I'acuolated  leiieocvte  apparently  enclosing  a  dwaifed  and  slirunten  iie^.eiil 
26.    Remains  of'  a  sin  iinken  spherical  form. 

(E.  F.  Fabkr.  /><-.) 


i 


AXIMAL   I'AKASlTliS   AS  CAUSKS   OI-    DIS  i:  ASK.  I9I 

In  all  forms  of  the  disease  the  so-called  malarial  paroxysm  -which  in 
typical  cases  is  characterized  by  the  occurrence  of  chills,  fever,  and  sweat- 
ing— develops  at  the  time  which  corresponds  to  the  occurrence  of  sjjorula- 
tion  in  the  parasite.  The  symptoms  must  depend  upon  the  presence  of 
some  poison,  although  all  attemjjts  at  the  isolation  of  such  a  body  have 
been  disappointing.  The  active  hemolysis  that  accompanies  all  forms 
of  the  disease  necessarily  throws  great  stress  upon  the  blood-forming 
organs,  and,  by  the  liberation  of  pigment,  gives  rise  to  deposits  which  are 
particularly  evident  in  the  liver  and  spleen.  The  changes  in  the  organs 
are  largelv  dependent  upon  the  duration  of  the  afTection.  Even  in 
recent  cases  leukocytes  containing  pigment  are  of  common  occurrence 
and  of  great  diagnostic  value ;  in  older  cases  the  number  of  these  cells  is 
sometimes  most  striking.  In  the  acuter  cases  of  malaria  the  hepatic 
changes  resemble  those  seen  in  certain  bacterial  infections;  the  organ 
is  swollen,  the  epithelium  granular,  sometimes  fatty,  areas  of  focal 
necrosis  occur  and  the  biliary  passages  are  not  infrequently  the  seat  of 
a  well-marked  catarrhal  cholangitis.  In  more  chronic  cases  the  pig- 
mentation is  marked  (slate-colored  liver),  the  fibrous  tissue  increased, 
and  not  infrequently  a  moderate  degree  of  red  atrophy  is  present.  In 
both  acute  and  chronic  cases  plasmodia  and  pigment  may  be  found  in 
the  capillaries.  The  spleen  in  acute  cases  is  soft,  the  pulp  dark,  the 
endothelium  proliferating  and  phagocytic,  and  parasites  abundant  both 
within  and  without  the  red  blood-cells.  In  chronic  malaria  the  spleen 
is  enlarged  (ague-cake),  firm,  cuts  with  resistance,  and  is  of  a  slaty  hue. 
The  fibrous  tissue  is  enormously  increased.  In  acute  malaria  the  renal 
epithelium  is  granular  and  sometimes  fatty;  the  kidneys  are  intensely 
congested,  occasionally  edematous,  and  soft.  Ewing  and  others  have 
demonstrated  plasmodia  in  the  Malpighian  tufts.  In  chronic  malaria 
a  moderate  diffuse  nephritis  with  some  increase  in  the  fibrous  tissue 
may  be  present.  The  bone-marrow  shows  more  or  less  hyperplasia 
and  pigmentation  and  commonly  contains  demonstrable  numbers  of 
Plasmodia,  many  of  which  are  sporulating.  Sometimes  the  marrow 
reverts  to  the  embryonal  type,  while  in  other  instances  the  proliferative 
changes  are  less  marked.  The  capillaries  of  the  gastro-intestinal  mucosa 
may  be  packed  with  parasites,  and  it  is  possible  that  this  explains  the 
marked  gastro-intestinal  symptoms  present  in  some  cases.  The  cere- 
bral symptoms  seen  in  malaria  may  be  attributed  to  massing  of  the 
parasites  either  generallv  or  locally,  or  to  the  toxemia.  The  brain  and 
cord  are  usuallv  edematous  or  h'yperemic;  and  minute  hemorrhages 
mav  be  present;'  structural  changes  are  recognizable  in  the  ganglion  cells, 
which  commonly  manifest  more  or  less  cnromatolysis  and  granular 
changes  in  the  dendrites  and  neurofibrils.' 

Other  protozoal  parasites  that  might  with  pro{iriety  be  described  as 
hemospori<lia  have  been  reported.  Lowit^  believes  he  has  demonstrated 
the  protozoal  origin  of  leukemia.  Graham  ^  and  Eberle  *  attribute  dengue 
to  parasites  resembling  those  of  malaria.  The  first-named  observer 
states  that  the  Culex  fatigans  is  the  mosquito  in  which  the  sexual  cycle 
of  the  parasite  is  completed  and  by  which  the  disease  is  disseminated. 

»  For  exhaustive  review  of  the  pathologic  anatomy  of  malaria  fcvtr.  .'^c 
Ewing,  "Tour.  Expcr.  Med.."  vol.  vi,  p.  119. 

'  "Die  Leukamie  als  Protozoeninfektion."  Wiesbaqen,  1900. 

'  "Medical  Record,"  1902,  vol.  xli.  p.  204. 

*  "New  York  Med.  Jour.."  Dec.  24.  1904,  P-  t^oj. 


192  GENERAL  PATHOLOGY. 


VERMES. 


The  vermes  (worms)  of  importance  in  human  pathology  belong  to  (i) 
trematodes,  (2)  cestodes,  or  (3)  nematodes. 

Under  the  name  distomatosis  or  distomiasis  is  included  a  number  of 
affections  occurring  in  man  and  lower  animals  and  due  to  trematodes, 
also  called  flukes.  Stiles^  suggests  that  the  following  clinical  forms  of 
distomatosis  be  recognized:  (a)  Ophthalmic  distomatosis,-  about  which 
we  have  little  accurate  information,  as  the  condition  is  exceedingly  rare; 
(b)  pulmonary  distomatosis,  or  parasitic  hemoptysis,  with  which  should 
be  mentioned  cerebral  distomatosis,  usually  secondary  to  pulmonary 
lesions;  (c)  hepatic  distomatosis ;  (g?)  pancreatic  distomatosis ;  (<?)  intes- 
tinal distomatosis;  (/)  venal  distomatosis. 

Pulmonary  distomatosis,^  also  called  parasitic  hemoptysis,  is  due  to 
the  Paragoniiniis  westcrmanii,  also  called  the  Distoma  westermanii,  Dis- 
toma  ringeri,  Distoma  pulmonale,  etc.  The  adult  parasite  is  8  mm.  to 
20  mm.  long,  4  mm.  to  8  mm.  broad,  and  2  mm.  to  5  mm.  thick.  The 
eggs  are  oval,  80  !>■  to  100  ,".  long,  50  ,".  to  go  ,".  broad,  and  possess  a  yellow- 
ish shell ;  when  hatched  they  give  rise  to  a  niiractdium,  of  which  we  possess 
little  accurate  information.  The  method  by  which  infection  in  man 
occurs  is  not  known;  it  has  usually  been  held  that  the  parasite  enters 
with  the  ingesta,  but  recent  more  accurate  knowledge  of  allied  parasites 
suggests  the  possibility  of  transcutaneous  infection.  In  man  the  disease 
is  characterized  by  bronchial  and  pulmonary  symptoms  and  the  expec- 
toration of  dirty  red,  or  reddish-brown  sputum  containing  the  eggs,  of 
which  twelve  thousand  may  be  discharged  daily.  Hemoptysis  occurs 
in  most  cases.  At  autopsy  the  parasites  are  found  in  the  bronchi  and  in 
irregular  caverns  in  the  pulmonary  tissues.  The  cavities  are  marginated 
by  areas  of  induration  associated  with  more  or  less  interstitial  pneumonia 
and  peribronchial  thickening.  Metastasis  to  the  brain  is  occasionally 
seen.  It  is  characterized  by  the  occurrence  of  areas  of  softening  the  per- 
ipheries of  which  are  infiltrated  by  mononuclear  cells ;  eggs  are  present 
in  the  affected  vessels.  Cirrhosis  of  the  liver  due  to  the  ova  is  sometimes 
found.  The  diagnosis  of  pulmonary  distomatosis  is  made  by  finding  the 
eggs  in  the  sputum. 

Hepatic  distomatosis  may  be  due  to  any  one  of  at  least  five  species  of 
parasite,  all  of'  v^hich  are  members  of  the  fasciolidce.  The  Fasciola 
hepatica  (comm  n  liver  fluke,  Distoma  hepaticum)  is  18  mm.  to  35  mm. 
long,  and  8  mm.  to  15  mm.  wide;  the  surface  is  spiculated,  the  apices  of 
the  spines  being  directed  backward.  The  yellowish-brown  eggs  are  oval, 
125  ,".  to  150  ,".  long,  and  70  //.  to  80  //  thick;  they  are  present  in  the  feces 
during  the  active  stages  of  the  disease.  The  Dicrocceliiim  lanccaUim 
is  a  much  smaller  liver  fluke  and  rarely  affects  man. 

The  Opisthorchis  felineus  (Distomum  lanceolatum,  Distomum  sibi- 

*  I  shall  take  some  liberties  with,  but  in  a  sjeneral  way  will  follow,  the  admir- 
ably outlined  plan  suggested  by  Charles  Wardell  Stiles,  Hygienic  Laboratory  Bul- 
letin, No.  17,  1904.  From  the  bibliography  given  in  that  publication  the  literature 
of  the  subject  may  be  followed. 

^  I  shall  make  no  further  reference  to  this  affection ;  those  interested  may 
consult  Stiles'  monograph. 

^Stiles,  "Proceed.  Path.  Soc.  of  Phila.,"  Feb.  i,  1901,  vol.  iv,  p.  61.  Tani- 
guchi,  "Archiv.  f.  Psychiatrie  und  Nervenkrank.,"  vol.  xxxviii,  1904.  Mackenzie, 
"Jour.  Amer.  Med.  Assoc,"  April  30,  1904,  p.  1133. 


ANIMAL   I'AkASITKS   A>   i  Ai  :^i.-.   . » i-    DISEASI-  I  <;  ^ 

nsLiiiin  IS  8  mm.  to  15  mm.  long,  1.25  mm.  to  2.5  mm.  Kroau,  nai  and 
lanceolate  and  without  surface  spines.  The  eggs  are  oval,  ^o  -<  tn  ^6  n 
by  1 1  ,'' to  15 /'.  with  an  operculum  at  the  smaller  pole.     The-  /;/> 

ncrccrca  is  9  mm.  to  i  2  mm.  long,  2  mm.  to  5  mm.  broad,  laii  aid 

with  spiculated  skin;  the  eggs  are  oval,  34  ,"  by  i(>  ,"  to  .m  ,".  The 
i^pi^tliorchis  sinensis  is  10  mm.  to  20  mm.  long,  2  mm.  to  5  mm.  broad, 
lanceolate  or  oval  and  without  spines.  The  dark  brcjwn,  oval  eggs  are 
27  ,'i  to  30  ,'«  by  1 5  ,".  to  I  7  ,".. 

In  hepatic  distomatosis  the  liver  is  enlarged,  the  capsule  thickened, 
the  interstitial  tissue  increased  (cirrhosis),  and  the  bile-ducts  dilated  and 
inflamed.  The  parasites  and  eggs  are  usually  demonstrable  in  the  biliary 
passages.  The  hepatic  cells  show  granular  or  fatty  changes,  the  per- 
iphery of  the  lobule  is  frequently  infiltrated  by  round  cells,  and  areas  of 
necrosis  are  usually  ]»resent. 

Of  pancreatic  distomatosis  but  little  is  known.  It  is  caused  by 
the  migration  of  flukes  into  the  pancreatic  duct  and  is  characterized  by 
dilatation  and  inflammation  of  the  ducts,  necrosis  of  the  pancreatic 
tissue,  interstitial  pancreatitis,  and  sometimes  areas  of  hemorrhage. 
The  condition  may  be  produced  by  some  o.f  the  flukes 
that  are  the  cause  of  hepatic  distomatosis. 

Intestinal  distomatosis  is  a  manifestation  of  the 
irritant  action  ot  flukes  or  their  eggs  upon  the  intestinal 
mucosa.  Of  the  relatively  large  numl^er  of  trematodes 
that  are  occasionally  found  in  the  intestine  l)ut  little  is  ''cixi.''^ 
known  as  to  their  special  action  on  this  part  of  the-  ',-i^.^"h^  i«0^ 
alimentary  canal.  Stiles  describes  the  parasites  found,  -fl  >  -1^ 
and  those  interested  may  consult  his  paper.  ^ 

The  trematodes  to  which  reference  has  been  made  ^ 

in  the  preceding  paragraphs  are  flat,  oblong  or  conical, 
hermaphrodite  worms  possessing  two  suckers  (hence  the  j^> 

name  di-stoma);  the  anterior  or  oral  sucker  is  in  front 
of  the  mesiallv  placed  second  sucker,  called  the  aceta-      Fig.  ioj."Fa.->ii..la 
bulum.    The  oral  sucker  leads  into  a  short  tube  (pharynx  Hefatica. 

and  esophagus)  which,  anterior  to  the  acetabulum, 
bifurcates,  giving  rise  to  two  convoluted  tubules,  one  of  which  traverses 
each  side  of  the  parasite,  and  terminates  as  a  blind  sac  in  the  posterior 
part  of  the  worm.  There  are  usually  two  round  or  lobate  testes,  one 
on  each  side,  and  an  extremely  complex  uterus  and  ovisacs  in  which 
the  developing  eggs  may  be  detected.  The  parasite  possesses  no  anus. 
although  an  excretory  pore  may  be  recognized.  The  hatched  eggs 
develop  into  a  miracidium,  for  the  further  evolution  of  which  a  second 
host  is  necessary.  -, 

Venal  distomatosis/  also  called  endemic  or  parasitic  hematuria. 
bilharzia  disease,  Bilharzia  ha?matobia  infei  in,  Bilharzia  distomatosis. 
or  Bilharziosis,  is  a  disease  affecting  the  bla  der,'  rectum,  portal  system, 
and  liver,  and  caused  by  the  Schistosoma  haematobium  (Bilharzia  hama- 

'  See    foot-note.    p.    181.     Milton,    "Lancet,"    March    28.    iQop.     Svmmcrs. 
•Jour,  of  Path,  and   Bact..'   nectinbcr,   looi.     Douglas  and  Hardy.   '  ' 
Oct.    10.    1903.      RaiTertv,       Med.    Record,"   June   4.    1004.      Rankin.    '   ! 
Med.  Jour."  Julv.   1904.'     O'Neill.  'Boston  Med.  and  Surg.  Jour.."  f)ct.  -,.     -    . 
Sandwith.  "Practitioner,"  (^ct.,  IQ04.     Clavl-m-Greene.  "Lancet,"  r)ec.  17.  1004. 
Kautsky-Bey,  "  Zcit .  f   klin    Mid  ."  doj.  B-'l.  ;.-.  !•    i-ji.      Lctulle.  'Sv..!.'  Bi..].." 
Paris,  April  8,  iqo? 
14 


194 


GENERAL   PATHOLOGY. 


tobia,  Distoma  haematobium,  blood,  fluke).  Unlike  the  flukes  already 
described  this  parasite  is  not  hermaphroditic.  The  male  is  lo  mm.  to 
15  mm.  long,  i  mm.  wide,  the  lateral  margins  curved  toward  the  ven- 
tral aspect,  forming  the  canalis  gynaecophorus  for  the  reception  of  the 
female.  The  dorsal  surface  is  marked  by  small  warty  projections 
permitting  the  parasite  to  cling  to  vessel  walls.  The  female  is  20  mm. 
long  and  considerably  thinner  than  the  male.  The  surface  is  also 
spiculated;  the  oral  sucker  and  acetabulum  of  the  male  or  female  are 
not  unlike  similar  structures  in  other  flukes.  The  parasites  inhabit 
the  portal  circulation,  and  the  morbid  processes  with  which  thev  are 
associated  are  attributed  to  the  injury  produced  by  the  spiculated'  ova, 
of  which  the  female  produces  large  numbers;  the  eggs  are  oval,  120  ,". 
to  160  !>■  long,  50  !>■  to  60  //  broad,  with  a  sharp  spine  projecting  from 
one  end;  laterally  placed  spines,  occasionally  observed,  are  thought 
by  Looss  to  be  malformed  eggs.  During  life  the  eggs  are  found  in  the 
urine  and  in  the  feces.  Postmortem  they  are  abun- 
dant in  the  vesical  wall,  rectum,  ureter,  and  liver. 
Urinary  fistula  are  not  uncommon;  vesical  lithiasis 
occurs  in  ten  to  fifteen  per  cent,  of  the  cases.  The 
eggs  in  the  bladder  wall  give  rise  to  a  chronic  cystitis, 
to  marked  connective-tissue  proliferation  and  hyper- 
trophy, and  to  papillomatous  or  polypoid  growths  of 
the  mucosa.  The  ureters  may  be  as  large  as  the  small 
intestine;  hydronephrosis  and  pyonephrosis  occur. 
When  the  rectum  is  involved,  the  mucosa  resembles 
a  rich  red  velvet,  and  numerous  polypoid  papillomas 
may  be  present.  The  liver  is  usually  enlarged  and 
may  weigh  three  kilo.  The  connective  tissue  is  enor- 
mously increased,  the  incised  surface  of  a  peculiar 
drab  color,  and,  in  addition  to  the  cirrhosis,  properly 
prepared  sections  show  the  presence  of  typical  eggs 
or  shells,  or  eggs  with  lateral  spines.  Letulle  has 
described  a  special  form  of  phlebitis  due  to  the 
parasite. 

The  diagnosis  of  venal  distomatosis  during  life 
is  based  on  the  demonstration  of  spiculated  eggs, 
particularly  in  the  few  drops  of  bloody  urine 
voided  at  the  end  of  micturition.  An  important  diagnostic  point 
is  the  notable  increase  in  eosinophiles  usually  present.  In  50  cases 
examined  by  Douglas  and  Hardy  the  average  percentage  of  eosino- 
philes was  38.48.  The  lowest  percentage  was  1.3;  in  rare  cases  one- 
half  of  the  leukocytes  are  eosinophiles.  For  finding  the  parasites 
postmortem,  Sandwith  recommends  that  the  blood,  from  the  portal 
vein,  be  scooped  out  with  a  spoon  and  placed  in  a  glass  dish;  in  the 
thin  layers  secured  in  this  way  the  parasites  may  readily  be  recognized. 
The  number  of  parasites  in  the  portal  blood  is  usually  not  large,  although 
in  one  of  Sandwith's  cases  400  were  found. 

The  second  important  group  of  vermes  affecting  man  are  the  ces- 
todes  or  tapeworms.  The  fully  formed  adult  worm  (strobila)  consists 
of  a  head  (scolex),  to  which  are  attached  the  flattened  segments  (pro- 
glottides), of  which,  in  some  of  the  tapeworms,  a  thousand  or  more  may 
be  joined  end  to  end,  forming  a  band-like  bodv.     The  neck  is  usually 


Fig.  103. — Schistosoma 
h^matobium,  ^l\le 
AND  Female,  the 
Latter  ix  the  Can- 
A  L  I  s     G  Y  N .«  c  o  - 

PHORUS      OF      the 

Former  .  —  (After 
Leuckart. — Gould.) 


ANIMAL   I'AKASITKS   AS  CAUSES  Of   DISEASK.  I()5 

composed  of  ininiaturc  proglottides.  Each  fully  devclopffi  j,; 
or  segment  is  hermaphroditic,  containing  a  uterus  and  its  appi 
testicular  gland  and  duct;  the  sexual  opening  (genital  pore)  is  lucaLcil 
in  the  margin  of  the  proghjttis  in  the  Ta'nia>  an<l  near  the  center  of  the 
flattened  surface  of  tlie  Dihothriocephalida".  The  head  is  sunnountcd 
by  special  organs  enabling  the  parasite  to  attach  itself  tf)  the  intestinal 
mucosa;  the  bodies  accomi)lishing  this  are  either  sintorial  discs  or 
grooves,  or  a  rostclliini  armed  with  booklets;  some  of  the  tapeworms  are 
supplied  with  suctorial  discs  and  also  the  booklets.  Parasites  possess- 
ing the  latter  structure  are  called  armed  tapeworms. 

Like  a  number  of  other  animal  parasites  to  which  reference  has 
been  made,  the  tapeworms  do  not  complete  their  development  in  a 
single  host.  Most  of  the  cestodes  are  adult  parasites  in  man  ami  pass 
their  so-called  larval  stage  in  one  of  the  lower  animals.  The  eggs 
escaping  from  the  human  intestine  enter  another  host,  in  the  tissues 
of  which  a  cyst  containing  the  developing  larva*  is  produced;  man 
consuming  meat  containing  these  parasites,  digests  the  capsule,  and 
liberates  the  parasite  in  his  own  alimentary  canal.  With  regard  to 
the  Taenia  echinococcus,  man  occupies  the  position  of  host  for  the 
larvje,  the  adult  worm  occurring  in  the  dog. 

Frequently  a  tapeworm  in  the  alimentary  canal  is  not  evinced  by 
any  conspicuous  manifestations;  in  other  cases,  however,  the  nutrition 
of  the  host  is  profoundly  influenced.  The  local  irritation  produced  by 
the  worm  is  usually  slight,  and  an  important  question  has  been  raised  as 
to  whether  or  not  these  parasites  produce  definite  poisons.  Massineo 
and  Calamida.'  Faber  and  Bloch,-  Isaac  and  von  den  Velden,^  and  others 
believe  that  in  the  dibothriocephalus  some  hemolytic  substance  is 
produced,  through  the  action  of  which  the  accompanying  anemia  is 
brought  about.  Schauman  and  Talqvist  find  that  different  specimens 
of  the  dibothriocephalus  are  not  of  equal  toxicity,  and  this  may  explain 
whv  in  some  cases  the  worm  causes  anemia  while  in  others  it  does  not. 
The  following  are  the  important  cestodes  occurring  in  man. 

Taenia  mediocanellata  ^  or  saginata,  or  beef  tapeworm.  The  head  is 
quadrate.  1.5  mm.  to  2.25  mm.,  surmounted  by  four  suckers  arranged 
in  a  quadrangular  outline,  in  the  center  of  which  is  a  fifth  rudimentary 
sucker  or  flattened  groove ;  the  head  is  void  of  booklets,  hence  the  worm  is 
known  as  the  "unarmed  tapeworm."  The  head  is  attached  to  a  slen- 
der neck  varying  in  length  and  terminating  in  the  first  link,  proglottis, 
zooid,  or  segment — terms  used  synonymously.  The  segments  when 
fullv  developed  are  between  8  mm.  and  10  mm.  broad  and  about  18  mm. 
long,  and  thicker  than  the  ])roglottides  of  the  taenia  solium;  like  all  tape- 
worms, each  segment  is  hermaphroditic.  The  genital  pores  are  placetl 
laterallv;  the  uterus  shows  dichotomous  branching  more  characteristically 
than  the  Taenia  solium;  the  number  of  branches  varies,  but  is  approx- 
imately fifteen;  the  segments  are  commonly  thrown  off  spontaneously, 
while  the  Taenia  solium  rarely  sheds  a  single  proglottis.  The  length 
of  the  worm  varies  greatly;  the  number  of  segments  may  exceed  1000. 

'  "Jour.  Med.  Vet.  ct  Zootcch.."  Sept.,  iQOi. 

*  "  Hospitalstinde  Copenhagen,"  vol.  xlvi,  No.  36. 

*  "Deut.  med.  Woch.."  1904,  xxx.  p.  0S2. 

*  Braun,  "Die  thierischen  Parasitcn  des  Menschpn,"  1903.  Rciss.  "Munch. 
med.  Woch,"  Feb.  q,   1004.  p.  260. 


196 


GENERAL   PATHOLOGY. 


and  the  entire  worm  may  measure  between  four  meters  and  ten  meters. 
The  ova  constantly  appear  in  the  stools,  and  the  segments  show  the 
uterus  distended  with  them.  Each  ovum  is  ovoid — egg-shaped — with 
a  striated  outer  membrane  and  a  thick  shell;  the  length  is  30  /a  and  the 
width  25  //.  The  eggs  and  segments  discharged  in  the  feces  are  ingested 
by  the  ox;  the  larva  or  juvenile  parasite  is  liberated,  and  reaches  the 
muscles,  for  the  most  part,  although  it  has  been  observed  in  the  heart, 
lungs,  and  liver.  At  the  point  of  deposit  there  develops  a  cyst,  varying 
in  size  from  2  mm.  to  2  cm.  in  diameter,  whitish  in  color,  and  ovalin  out- 
line. In  this  is  the  larval  worm;  the  cyst  wall  is  of  connective  tissue. 
In  this  stage  the  parasite  is  known  as  cysticerciis  saginata.  Beef  rarelv 
contains  many  such  cysts,  and  their  small  size  not  uncommonly  causes 

them  to  be  overlooked.  Beef  con- 
taining the  cysts  is  said  to  show 
"measles."  It  is  not  known  that  man 
suffers  from  cysticercus  saginata. 

Taenia  solium,  also  known  as  the 
pork  tapeworm,  solitary  tapeworm, 
and  armed  tapeworm.  The  name 
Taenia  solium,  or  solitary  tapeworm. 


Fig.  104. — T.«NiA  saginata. — {Gould.) 


Fig.  105. — Cephalic  End  of  T.enia  saginata. 
.\.  Retracted  head.     B.  Extended  head. 


is  not  appropriate,  as  the  pork  tapeworm  is  more  commonly  multiple  than 
the  Tasnia  saginata;  indeed,  Leidy  regarded  the  latter  as  rarely  multiple. 
The  adult  parasite  is  a  soft,  white,  band-like  worm,  rarely  over  four 
meters  in  length.  The  head  is  round,  0.5  mm.  to  i  mm.  in  diameter; 
there  are  four  discoid  or  cup-like  suckers  and  a  centrally  placed  papilla, 
proboscis,  snout,  or  rostellum,  surmounted  by  two  rows  of  booklets,  each 
row  having  from  twelve  to  fourteen  booklets ;  the  booklets  of  the  inner 
row  are  the  larger.  The  neck  is  very  thin,  about  2.5  cm.  in  length,  ter- 
minating in  the  gradually  developing  segments.  The  segments  are  from 
10  mm.  to  12  mm.  long,  and  from  6  to  8  mm.  broad.  The  proglottides 
differ  in  this  respect  from  those  of  the  beef  tapeworm;  the  segments  nearer 
the  head  may  be  much  broader  than  long.     The  uterus  is  broader,  coarser, 


AMMAI.    I'AKASrnOS    AS    CAlSI'ISoi     DISI.ASI. 


lo: 


and  tlie  median  tube  larj^cr,  witli  fewer  branthes — six  ia  Icn,  l»ut  hiile 
over  half  tlie  nunil)er  eoinnionly  seen  in  the  beef  tapeworm.  The  c^^s 
are  about  the  same  size  as  tliose  of  the  Ta'nia  sa^inata,  .^o  /'  to  35  /«,  but 
more  sjihcroid. 

Tlio  scolex,  larval,  juvenile,  nr  cysticercus  form  of  the  Tania  solium 
lias  loni:[  been  known,  but  Kuchennieister,  by  feeding  experiments,  dem- 
onstrated that  the  so-ealled  cysticercus  cellulosae  is  but  the  larval  form  of 
the  Taenia  solium.  The  larva'  are  most  fre((uently  developed  in  the  hog, 
gaininj;^  ingress  as  already  described  when  considering  the  similar  stage 
in  the  l)eef  tapeworm.  The  habits  of  the  hog,  however,  render  measles 
much  more  common  in  that  animal  than  in  the  ox.  Either  l)y  the  acci- 
dental contamination  of  the  hands,  and  subsequent  ingestion  of  the  ova, 
or  possiblv  bv  regurgitation  during  vomiting,  occasionally  the  ova  reach 
the  human  stomach;  as  in  the  beef  larvae  in  the  ()x,  the  liberated  larva* 
of  the  solium  in  man  may  become  widely  disseminated.  Cysticercosis, 
most  common  in  the  insane,  is  usually  the  result  of  coprophagy.  When 
the  parasite  lodges,  a  cyst  follows,  and  whether  in  man  or  the  hog,  a 


Fig.  106. — HtAi. . 

ECC  OF    TiENIA    SOLHJM.- 


()\  THK  Ru.in. 
■{Gould.) 


.      107.— CVSTK  t.KlLS    (111      :         \  (UMPI.F.TION 

OF  Head  P'ormation.  —  (^1//<'  Ltuckart. — Copiin 
and  Bn'an.)     X  n  diameters. 


■  mcasle"  results.  The  cyst  formed  is  much  larger,  as  a  rule,  than  in  the 
ox,  and  may  attain  the  size  of  20  mm.,  the  beef  measle  rarely  exceeding 
7  mm.  While  the  beef  measle  is  rarely,  if  ever,  seen  in  man,  this  form  is 
not  infrequent.  The  method  of  invasion  is  probably  the  same  from  both 
cvsticerci:  both  the  embryos,  when  liberated  in  the  stomach,  have  six 
hooklets,  arranged  in  pairs,  by  which  they  tear  and  i)ropcl  their  passage 
through  the  wall  of  the  viscus. 

There  are  a  number  of  tapeworms  of  the  genus  Hymenolepis*  occur- 
ring in  man.  The  most  important  of  these  is  the  Hymenolepis  nana,  also 
called  the  Tania  nana.  The  parasite  is  5  mm.  to  ,^5  mm.  long,  and  0.5 
mm.  to  0.9  mm.  in  breadth.  The  head  is  round,  215  :>  to  480  n  \r\  diam- 
eter; it  possesses  four  suckers  and  a  retractile  rostellum  anned  with 
twentv-four  to  twenty-eight  hooklets  arranged  in  a  single  row.  The 
hooklets  varv  in  length  from  4  "  to  18  .".  The  length  of  the  proglottides 
is  much  less  than  their  breadth;  the  genital  pores  open  on  the  left  side 
near  the  anterior  border  of  the  proglottis.     The  fully  forme  '         •     tits 

»  Ransom,  Bulletin  Xo.  iS.  ..f  th,    TIv,'i.-ni.-  Lal...rat<.rv.  1004.  1.1  '^Ifd 

description  of  these  parasites. 


198 


GENERAL   PATHOLOGY. 


are  distended  with  eggs;  a  single  proglottis  may  contain  as  manv  as  100 
ova.  The  size  of  the  egg  varies  materially;  Ransom  gives  from  36  /j.  by 
3  2  //,  to  56  /x  b}^  42  //.  Infection  by  the  parasite  is  not  common ;  Ransom 
has  been  able  to  collect  106  cases.  Most  of  the  patients  are  males,  and 
usually  children.  Another  parasite  belonging  to  the  same  genus  is  the 
Hymenolepis  diminuta  {Taenia  favo punctata);  the  length  of  the  strobile 
rarely  exceeds  60  mm.,  the  width  2.5  mm.  by  4  mm.  The  gloljular  head 
measures  200  //  to  600  //,  possesses  suckers  and  rudimentary  unarmed  ros- 
tellum;  the  eggs  are  round  or  slightly  oval,  64  //  to  80  ,"-  in  diameter.  The 
parasite  is  also  found  in  rats.  The  larvae  are  developed  in  meal  moths 
and  beetles. 

Taenia  Echinococcus^  or  Dog  Tapeworm, — The  sexually  mature  worm 
inhabits  the  intestine  of  the  dog  and  wolf.     It  is  an  insignificant  parasite 
in  appearance  when  compared  with  the  larger  forms,  rarely  attaining  a 
length    of    five    millimeters.      When 
fully   developed,   there   are   five   seg- 
ments;  the  anterior  is  slender  and  is 
continuous   with  the  head;   the   fol- 


FlG.   I 


Hymenolepis  diminuta. 


Fig.   109. — T.tNiA    echinococcds. — (Ajler  Leuckart. 

— Coplin  and  Bevan.) 
a.  .\dult  parasite,     b.  Head   of  echinococcus  veterin- 

orum.     On   the  left,  a  detached  hooklet,  as  seen 

in  tiiud  from  cyst. 

lowing  segment  is  the  shortest,  and  the  posterior,  the  longest.  Often  more 
than  half  of  the  length  of  the  parasite  is  in  the  last  segment ;  from  time 
to  time  the  large  link  is  thrown  off,  so  that  is  is  not  uncommon  to  find  but 
the  three  proglottides.  The  worm  is  short  lived,  and  is  probably  the 
least  prolific  of  the  cestodes ;  this  is  compensated  for  by  the  proliferative 
power  of  the  parasite  in  the  juvenile  or  larval  stage.  The  anterior  seg- 
ment, or  scolex,  is  surmounted  by  four  suctorial  discs,  anterior  to  which, 
between  the  quadrately  placed  sucking  discs,  is  the  rostellum,  with  its 
booklets,  numbering  from  thirty  to  forty.  The  adult  worm  is  not  found 
in  man.  The  ova  thrown  off  by  the  parasite,  entering  the  alimentary 
canal  of  man  and  some  lower  animals,  hatch  the  embryo,  which,  wander- 

'  Lyon,  "Virginia  Med.  Semi- Monthly,"  Jan.  10,  1902.  Melnikow-Rasweden- 
kow,  "Zeigler's  Beitr.,"  1901,  Bd.  iv,  Stippl.  MacPhatter,  "St.  Louis  Med.  Re- 
view," Jan.  28,  1905.  Beha,  Inaug.  Diss.  Freiberg,  1904.  Deve,  "C.  R.  Soc.  de 
Biol.,"  Tome  v,   1903,  p.   1369. 


AM  MAI.    I'AKASITKS   AS  CAUSKS  Ol"   DISEASE  IQQ 

injj:  into  the  tissues  of  some  or^an,  develops  into  a  cyst — the  encysted 
parasite.     These  cysts  ocexir  in  three  forms: 

I.  Echinococcus  scolicipariens,  echinococcus  granulosus,  or  echino- 
coccus  veterinoruni,  is  a  lijaililcr-like  ryst,  varying'  in  size,  often  5  cm. 
to  15  cm.,  or  even  20  cm.,  in  (hamcter.  The  wall  of  the  cyst  is  formed 
of  two  layers,  as  a  rule,  easily  distinguished  from  adjacent  structures 
and  from  each  other.  The  outer  layer  is  supplied  by  the  invaded  organ, 
and  is  called  the  cuticular  membrane,  the  tissue  of  which  shows  distinct 
lamination;  the  inner  layer,  which  is  finely  granular,  constitutes  the 
granular  or  parenchyma  layer.  When  the  cyst  has  attained  a  diameter 
of  2  cm.  to  10  cm.,  the  develojoment  of  brood  capsules  begins.  These 
will  be  found  attached  to  the  granular  layer,  first  as  dot-like  bodies, 
later  as  distinct  cysts,  in  which  many  young  parasites  occur;  hence 
thev  are  spoken  of  as  brood  cysts,     the  heads  or  scolices,  ])rojecting 


Kn;.  110.     HvPAriu  Cvsr,  sHowiNC.  Datciitkb  Cysts. 
In  the  lower  pari  of  the  tigure  '.is  a  whifish   mass  cont.-.ininK  par's  of  the  «;alU  of  ruptureil  .1 
thick  wall  of  the    mother  cvst  is  well  shown.      (Removed  tiv  Or.  II.  R.  Umx  from  the 
twenty  seven  years.    The  illustration  is  two  thirds  the  natural  size.    \\eiKht.  t07  Km.    I  In   j*. .-. ■, 

into  the  cvst,  are  about  o..^  mm.  long,  have  developed  four  suckers,  and  a 
rostellum'with  attached  booklets;  the  interior  shows  a  vascular  system 
and  sometimes  granular,  chalk-like  bodies  within;  at  times  a  parasite 
may  be  found  with  the  scolcx  invaginated  into  the  pf)sterior  part  of  the 
bodv,  as  thr)ugh  rctraitcd. 

2.  Echinococcus  hydatidosus,  Echinococcus  altricipariens,  <t  Echmo- 
coccus  hominis,  is  characterized  liy  the  development  of  daughter  cysts. 
])robablv  from  degeneration  of  the  brood  capsules  already  described. 
From  the  daughter  cvsts  another  generation  of  parasites  may  develop, 
forming  still  another'  series  of  cysts.  The  numr>er  of  daughter  cysts 
mav  V)e  enormous:  as  given  bv  Thoma,  looo. 

3.  Echinococcus  multilocularis  bears  little  resemblance  to  the  forms 


200  GENERAL  PATHOLOGY. 

just  mentioned;  the  cysts  never  attain  any  great  size,  but  occur  in  enor- 
mous numbers.  The  Hver  is  the  common  site  of  this  form,  which  is 
very  rare  in  the  other  organs.  Eariier  observers  regarded  the  growth 
as  an  alveolar,  colloid  tumor.  The  cysts  rarely  attain  a  diameter  of 
over  one  centimeter,  are  spheric  or  ovoid,  the  wall  formed  bv  a  dense 
connective-tissue  membrane,  which,  under  the  microscope,  may  con- 
tain still  smaller  alveoli;  the  alveoli  are  filled  with  a  more  or  less  gela- 
tinoid  or  colloid  material  containing  a  few  of  the  histologic  elements 
of  the  scolex.  Often  only  on  prolonged  examination  can  these  be 
demonstrated.  The  cysts  may  communicate  with  one  another.  From 
careful  recent  studies  Melnikow-Raswedenkow,  Deve  and  others  are 
convinced  that  multilocular  echinococcal  disease  is  due  to  a  special 
jjarasite.  The  geographic  distribution  of  the  two  forms  is  not  the  same; 
there  are  areas  in  Europe  in  which  the  multilocular  form  is  common  and 
the  classic  echinococcus  is  almost  unknown. 


m 


Fig. 


.>. 


Ill- — Echinococcus.  A  Group  of  Scolices. 
— (From  Dr.  Loux's  case,  see  Fig.  no.  -J-in. 
obj.;  i-in.  oc.) 


Fig.  112. — Echinococcus. 
Scole.x:     j,  pedicle   of  attachment  to  endocyst.     Just 
above    are    shown    the    somewhat     disarranged 
booklets. — (From  Dr.  Loux's  case,  see  Fig.   no. 
Jin.  obj.;  ^-in.  oc.) 


Echinococcal  cysts  may  occur  in  almost  any  part  of  the  body.  In 
over  fifty  per  cent,  of  the  cases  the  liver  is  affected.  The  lungs  are  in- 
volved in  about  ten  per  cent.,  kidneys  ten  pef  cent.,  the  muscles,  sub- 
cutaneous tissues,  and  bones,  ten  per  cent.,  central  nervous  system  five 
per  cent.,  and  the  remainder  distributed  in  the  sexual  organs,  spleen, 
heart,  eye  and  orbit;  of  the  latter  about  fifty  cases  are  on  record.  Mar- 
shall could  find  but  three  cases  in  which  the  eyeball  was  involved. 
Occasionally  the  cysts  are  in  the  myocardium,  and  there  are  recorded 
instances  in  which  a  cyst  loose  in  the  circulation  caused  death  by  occlud- 
ing the  pulmonary  artery.^ 

Demonstration. — The  diagnosis  of  echinococcus-cyst  is  commonly 
based  upon  finding  the  booklets  or  scolices.  The  presence  of  a  fluid 
with  a  comparatively  low  specific  gravity,  and  nonalbuminous  or  con- 
taining but  a  minute  trace  of  albumin,  should  always  be  looked  upon 
as  indicating  an  echinococcus  collection.  When  the  fluid  is  clear  and 
contains  but  a  small  quantity  of  suspended  material,  sedimentation 
^  Quill,  "Jour,  of  Royal  Army  Med.  Corps,"  April,  1904. 


AM  MAI.    I'AKASITKS   AS  CAUSKS  OF   DISKASK. 


;oi 


l-ICi 


II,}.— ErHlNO^X)c- 
^l's-HooKI.  KTR.— 
{From  Dr.  Lotus's 
case,  vc  Fifj.  no. 
}-in.  obj.;    t-in.  oc.) 


shouUl  be  pcnnittcd  to  lake  i)laic,  an<l  the  sediment  may  be  further 
brought  together  by  the  centrifuge,  if  necessary.  A  small  quantity 
of  the  setliment  is  placed  on  a  slide  in  the  same  manner  as  clirected  fcjr 
urine;  examination  made  by  the  ^-inch  objective  will  usually  show 
the  booklets  c[uite  plainly.  Occasionally,  coccidial  cysts,  and  possibly 
cysts  arising  from  other  causes,  contain  sickle- 
shaped  bodies,  which  may  mislead  the  inexperienced. 
The  booklets  of  the  echinococcus  have  on  the 
concave  side  a  knob,  or  protuberance,  or  hump, 
the  appearance  of  which  is  not  fully  reproduced  1»\' 
anvthing  with  which  the  author  is  familiar.  The 
Ijrood  capsules  and  contained  scolices  can  rarely  be 
demonstrated  in  the  fluid  drawn  from  such  cysts  by 
tapping.  If,  however,  the  cyst  wall  be  accessible, 
gentle  scraping  will  usually  detach  the 'capsules,  some 
of  which  may  escape  rupturing.  These  are  l)est  shown  on  the  slide 
under  comparatively  low  magnification — i-inch  or  ^-inch  objective. 
(See  Figs,  iir  and  112). 

Occasionally,  the  cyst  may  be  inspissated  as  a  result  of  the  death  of  the 
contained   parasites.     Under  such  circumstances  the  contents  may  be 

cheesy,    resembling    the 
Mllll/f  ■  caseous     collections     of 

ml/f/My.  tul)erculosis    and  syphilis. 

The  demonstration  of  the 
booklets  in  this  material 
Ijecomes  somewhat  more 
dirticult.  A  considerable 
quantity  of  the  suspected 
material  should  be  washed 
in  alcohol,  the  alcohol 
drained  off,  and  the  wash- 
ing repeated;  this  may 
be  followed  by  washing 
in  ether  to  compiete  the 
removal  of  any  fat.  and, 
finally,  the  remaining  sedi- 
ment niay  be  transferred  to 
the  slide  and  examined  as 
already  directed.  If  these 
directions  are  carefully 
followed,  the  booklets  can 
usually  be  found;  some- 
times, however,  prolonged 
search  will  l)e  necessary. 
The  Dibothriocephalus 
latus'  (ia-uia  Lit.i.  I!<'th- 
rionpholKS  latus,  broad 
tapeworm)  is  the  largest 
cestode,  often  attaining  a 
length  of  tive  lo  ten  meters  and  comprising  2000  to  4000  progl-^  .1.  s. 

klin.  \V(^!i.,"  July  14.  1904.  P-  7' 

1087. 


Tic.  lis-  —  Fp.f.k-swimminc 
Embryo  of  the  Diboth- 
riocephalus Lati-s. — 
(Alter  Leuckart.— Gould.) 


V  I  (i.       I  14.  —  D  I  Bo  1  H  R  I  o  - 

OF.  PH  ALUS  Latus.— 
(.\jter  Leuckarl.— 
Gould.) 


I'lO.       116   — ClUB-S  H    W'    : 

Hkapop  thk  Dill" 

IMF  PH  ALUS        I.  A  T  ' 
(.XjUr  Uurk.trl    -Could.) 
.\.  Seen    fpini   thr  nine.       B. 
Seen  from  tl.it  !.urf.icc. 


.'^all, 


'  Flccksedcr  and  Stejskal,  "  Wien. 
"Amt-r.  Med.."  Dec.  24,   1904.  p. 


GENERAL  PATHOLOGY. 


Usually  but   one   parasite   is  present,   although   Zinn  reported   a   case 
in  which  there   were  seven. 

The  head  is  clavate,  rather  elongated,  has  a  long  elliptic  sucker  on 
each  side,  measures  about  1.5  mm.  long  by  i  mm.  wide,  and  is  without 
either  rostellum  or  booklets.  The  fully  developed  joints  are  from  two 
to  four  times  as  broad  as  long;  the  breadth  of  the  link  may  reach  1.8  cm. 
The  genital  aperture  is  always  on  the  ventral  aspect,  and  is  central. 
The  eggs  are  brownish,  oval,  60  //  to  70  //  in  length,  40  //  to  45  />.  broad, 
and  the  shell  is  furnished  with  a  lid  or  operculum,  through  which,  after 
some  months  in  water,  the  embryo  escapes.  Braun  has  observed  scolices, 
believed  to  be  of  the  dibothriocephalus,  in  pike  and  trout,  and  bv  feed- 
ing the  fish  to  dogs  has  led  to  the  development  of  the  tapeworm  in  the 

dog.     The  fully  grown  worm  is  said  to  be  the 
longest  of  tapeworms. 

Of  the  22  cases  reported  in  this  country 
all  of  the  patients  were  foreign  born.  The 
presence  of  the  parasite  in  the  intestine  is 
frequently,  although  not  constantly,  accom- 
panied by  an  intense  anemia  resembling  per- 
nicious anemia  and,  if  untreated,  is  frequently 
fatal.  The  recognition  of  dibothriocephalus  in- 
fection depends  upon  the  demonstration  of 
segments,  or  ova,  in  the  feces.  The  almost 
square  proglottides,  with  the  genital  openings 
centrally  located,  and  the  simple  convoluted 
uterus  containing  the  eggs,  render  the  diagnosis 
not  difficult.  The  slightly  elongated  ovum 
with  the  operculum  or  lid  situated  at  one  end 
usually  permits  a  ready  diagnosis. 

The  nematodes  occurring  in  man  are  cylin- 
drical worms  usually  tapering  at  both  ends. 
They  are  not  hermaphroditic  and  the  females 
are  generally  larger  than  the  males.  For  com- 
plete development  some  of  the  nematodes 
require  two  hosts;  others  may  pass  from  egg 
to  adult  worm  in  a  single  individual. 

The  Ascaris  lumbricoides  ^  is  a  yellowish  or 
yellowish-brown  worm,  varying  in  length;  the 
female  measures  about  15  cm.  to  30  cm.;  the 
male,  9  cm.  to  20  cm.  The  worm  is  striated 
transversely  and  possesses  four  longitudinal  bands.  Round  worms  are 
most  common  in  children,  occupying  the  upper  portion  of  the  small  in- 
testine, from  which  they  may  wander  into  the  bile-ducts,  stomach,  eso- 
phagus, nose,  Eustachian  tube,  and  larynx.  The  number  in  any  case 
varies;  rarely  are  they  present  in  large  numbers.  The  ova  are  ellipsoid, 
50  /J-  to  70  //  in  their  longest  diameter  and  35  //  to  50  //  in  width;  each 
egg  possesses  a  dense  enveloping  membrane. 

Collected  in  masses  ascarides  may  give  rise  to  intestinal  obstruction. 

'  See  Braun,  foot-note,  p.  iSi.  Vaullegeard,  "  Bull.  Soc.  Linn.  Normandie,"  56 
Ser.,  1901.  Wagner,  "Deut.med.Woch.,"  vol.  xxviii.  Pierantoni,  "  Gazz.Osped.," 
May  31,  1903.  Stott,  "Northwest  Medicine,"  Oct.,  1903,  p.  532.  Agar,  "Amer. 
Med.,"  June  21,  1902,  p.  1062.     Negresco,  "Soc.  de  Med.  Legale,"  Nov.  9,  1903. 


Fig.    1T7. — -Ascaris       lumbri- 


COIDES    .\ND    EgGS.- 

iind  Bcvan.) 


-(Copliii 


ANIMAL   I'AkASITKS  AS  CAUSES  OI'  DISEASE 

Ordinarily  the  worm  does  not  migrate  into  the  stomach,  nui  .x  (  .im-mi 
allv  it  does  so  and  is  vomited.  In  typhoid  and  scarlet  fevers,  or  other 
conilitions  in  which  the  ])atient  is  greatly  weakened  or  unconscious, 
the  parasites  mav  collect  in  numl)ers  in  the  esophagus  and  cause  collai>se 
of  the  larvnx  bv  pressure;  in  other  instances  they  wander  into  the  larynx 
and  may  occlude  the  chink,  giving  rise  to  fatal  asj)hyxia.  The  jirofes- 
sion  is  not  agreed  as  to  the  possibility  of  lunibricoides  penetrating  or 
perforating  the  intestinal  wall.  Usually  when  the  parasites  are  found 
in  the  peritoneal  cavity  they  have  escaped  through  perforations  due  to 
other  causes.  Evans  states  that  in  the  pig  they  are  frequently  found 
attached  to  the  mucosa,  and  numerous  cases  have  been  reported  in  man 
where  it  was  believed  that  the  worm  had  ])erforated  the  gut.  It  has 
usually  been  held  that  ascarides  ])roduce  no  poison.  Pierantoni  has 
shown  that  lumbricoides  yield  toxic  substances  which  ])roduce  mydriasis, 
and  is  of  the  opinion  that  the  nervous  symptoms  sometimes  seen  in  these 
cases  mav  be  due  to  toxic  substances  derived  from  the  parasite. 


Fig.     ii8.— O.xylkis     vermicularis. — (Coplin    and 

Bevan.) 

a.  Female,     b.  Male. 


Fig.  iig.— Male  Trichcxephalus,  Trichiuris,  "« 

Whipworm  . 
A  larRc  part  of  the  cephalic   end  of  the  worm    hiis 
transti-xed   a    fold    of    the    intestinal     mucosa. — 

iCohen.) 


The  Oxyuris  vermicularis  {tlircad-nvnn  or  piii-nvrm)  inhabits  the 
colon  and  rectum,  occasionally,  in  the  female,  involving  the  rectum  and 
vagina.  The  female  parasiteis  8  mm.  to  12  mm.,  and  the  male  3  mm. 
to  6  mm.  in  length.  The  oval  egg  is  30  ,"•  to  50  ."■  long.  20  ,'«  to  30  ," 
wide,  and  possesses  a  thin  shell  which  offers  some  protection  to  the 
contained  embrvo  when  subjected  to  the  influence  of  drying.  The  para- 
site wanders  from  the  anus  and  provokes  violent  itching,  which  not 
uncommonlv  causes  the  patient  to  lacerate  the  skin  by  scratching: 
this  in  turn" is  followed  by  infection,  giving  rise  to  refractory  inflamma- 
tion or  even  ulceration.  As  no  intermediate  host  is  necessary,  the 
patient  mav  be  reinfected  bv  ova  carried  to  the  mouth  on  the  hands 
soiled  bv  scratching.  From' the  time  the  ova  enter  the  mouth  about 
two  weeks  are  necessarv  for  the  adult  worm  to  appear  in  the  feces. 
The  worm  has  been  found  in  the  appendix  either  singly  or  in  masses, 
and  it  is  not  impossible  that  it  may  cause  appendicitis. 

The  round  worm  usuallv  known  as  the  Trichocephalus  dispar  (whip- 


204  GENERAL  PATHOLOGY. 

worm)  is  properly  called  the  Trichocephalus  trichiurus.  The  anterior 
two-thirds  of  the  parasite  is  thread-like  or  filamentary ;  the  remainder  is 
conic,  and  in  the  male  is  coiled  like  a  spring.  The  female  is  4  cm.  to  5  cm. 
long,  the  male  somewhat  shorter.  The  oval  eggs  are  50  //  long  and  20  !j- 
in  diameter,  and  at  each  end  possess  a  knob-like  protuberance.  The 
parasite  inhabits  the  colon,  particularly  the  cecum,  and  may  invade  the 
small  intestine  and  the  vermiform  appendix.  Girard^  has  shown  that 
the  cephalic  end  of  the  parasite  may  be  imbedded  in  the  mucosa  of 
the  appendix.  Askanazy  has  found  that  the  Trichocephalus  abstracts 
blood;  Becker  -  and  others  have  reported  cases  of  severe  anemia  showing 
no  improvement  until,  by  appropriate  treatment,  the  parasites  have  been 
removed. 

Strongyloides  intestinalis  ^  {Augitillula  intcstiualis,  or  Angiiillnla 
stercoralis)  is  found  in  the  upper  part  of  the  small  intestine;  rarely  the 
adult  worm  may  be  present  in  the  feces.  The  female  is  i  .5  mm.  to  2  mm. 
long,  0.05  mm.  to  0.07  mm.  broad.  The  male  has  not  been  identified,  and 
it  has  been  suggested  that  the  eggs  are  parthenogenetic,  giving  rise  to  both 
male  and  female  embryos.  The  body  tapers  anteriorly  and  posteriorly 
terminates  bluntly.  The  eggs  can  be  seen  in  the  interior  of  the  parasite, 
sometimes  containing  embryos;  when  hatched,  the  embryo  is  slender, 
actively  motile,  rarely  measuring  0.5  mm.  The  parasite  is  frequently 
present  in  diarrhea,  of  which  it  is  said  to  be  a  cause. 

Trichinosis^  is  a  disease  affecting  man  and  due  to  the  Trichina  spi- 
ralis, or  more  correctly  Trichinella  spiralis.  The  life  of  the  parasite  may 
be  divided  into  three  stages :  the  embryo,  the  encysted  larva,  and  the  adult 
worm.  According  to  Stiles,  the  encapsulated  larvs  have  been  found  in 
about  twenty-five  different  mammals,  including  man ;  it  is  most  common 
in  the  hog;  man  is  usually  infected  by  the  consumption  of  trichinous 
pork. 

In  the  muscle  the  parasite,  in  the  form  of  its  embryo,  will  be  seen  as  a 
coiled-up  worm  0.05  mm.  in  length,  surrounded  by  a  capsule  that  at  first 
is  translucent,  later  becoming  opaque,  and  eventually  calcareous.  If 
meat  containing  the  embr^^o  be  eaten,  the  capsule  is  digested  in  the 
stomach,  the  embryo  liberated,  and  its  final  development  into  the  adult 
worm  completed  in  the  small  intestine.  The  fully  grown  female 
trichina  measures  3  mm.  to  5  mm.,  the  male  about  half  as  much.  The 
adult  parasite  inhabits  the  duodenum  and  jejunum,  in  which  she  liberates 
the  embryos.  It  is  not  certain  whether  the  latter  are  thrown  off  in  the 
intestinal  cavity,  from  which  they  penetrate  the  wall  of  the  gut,  or  the 
adult  female  enters  the  intestinal  wall  and  discharges  the  embr\^os  in  the 
lymph  or  blood-vessels.  The  dissemination  of  the  embryo  is  evidently 
accomplished  through  the  blood  and  lymph  streams. 

Although  not  infrequently  found  in  other  tissues,  the  destination  of 

^  "Annales  de  I'lnst.  Pasteur,"   1901,  t.  xv. 

'"Deut.  med.  Woch.,"  June  26,   1902. 

^  "Jour,  of  Exper.  Med.,"  1901-05,  vol.  vi,  p.  75.  Exhatxstive  discussion  of 
the  parasite  Avith  full  bibliography,  by  Thayer.  See  also  Wainwright  and  Nichols, 
"Med.  News,"   1904,  p.  785. 

*  Stiles,  "Trichinosis  in  Germany,"  Bulletin  No.  30,  U.  S.  Dept.  of  Agricul- 
ture, 1901.  Ossipow,  "Ziegler's  Beitr.,"  1903,  Bd.  xxxiv,  Heft  2,  p.  253.  Schleif, 
"Deut.  Arch.  f.  klin.  Med.,"  Bd.  Ixxx,  p.  i.  Gould,  "Amer.  Med.,"  Sept.  26, 
1903,  p.  575.  Opie,  "Amer.  Jour,  of  the  Med.  Sci.,"  March,  1904.  Williams, 
"Jour.  Med.  Research,"  Julv,  1901. 


ANIMAL    I'AK  \SITi;S    AS  CAUSES  OT    DISK  ASK. 


^05 


the  worm  sccins  to  be  in  the  luuscles;  here  it  coils  up,  and  is  surrounded 
by  a  capsule  partly  produced  by  the  reaction  of  the  surrounding  tissue. 
The  changes  that  this  capsule  undergoes  have  already  been  noted.  It  is 
estimated  that  from  1000  to  2000  embryos  may  be  hatched  by  a  single 
female  trichina.  The  dissemination  of  these,  by  the  route  previously 
indicated,  may  be  associated  with  fever,  muscular  pains,  more  or  less 
edema,  and  even  paralysis.  A  small  ])crcentage  of  the  cases  terminates 
fatally.  A  recent  and  important  contribution  to  the  diagnosis  of  trichi- 
niasis  is  the  discovery  of  the  enormous  increase  of  the  eosinophile  cells  in 
the  blood.  The  lesion  in  the  muscle  is  essentially  a  i)arasitic  myositis 
through  the  activity  of  which  the  encapsulating  fibrous  tissue  is  produced. 
Dcnuvistratjo)!. — This  may  be  accomplished  by  teasing  the  suspected 
muscle  as  follows:  Clean  a  slide  thoroughly  and  breathe  upon  its  surface, 
thereby  slightlv  moistening  it;  upon  the  moistened  surface  lay  a  frag- 
ment of  the  muscle  to  be  examined;  with  needles  tear  the  fragment 
to  pieces;'  add  a  drop  of  glycerin  and   a  cover-glass;    examine  with  a 

J, -inch    or    ]-inch    objective.       In 
^  Ij  order  to  make  the  specimen   per- 

manent, wash  out  the  glycerin  with 
water,     delndrate     with     alcohol, 


lU 


Fic.  120. — Trichina  Spiralis. — {After  Lriickarl.) 
a.  Encapsulated.     6.  Same  with  calcific  capsule. 


Fig.  121.— CKPiiAi.ir  Kxtrf.mitv  of  Tnc  invkia  i«rn 

DENAI.IS("<)l.ll-\VoRI.l>  Hoi>KWORM")._   rRoriLK 

A.N'D  Front  View. — (Alter  l^utkarl. — Gould.') 


clear  in  creasote  or  oil  of  cloves,  apply  balsam,  and  cover.  The  frag- 
ment of  muscle  may  be  obtained  by  incision,  using  cocain  as  a  local 
anesthetic,  or  it  may  be  removed  by  a  punch  or  harpoon. 

Uncinariasis,^  also  called  ankylostomiasis,  results  from  the  presence 
in  the  intestine  of  a  hook-worm  of  the  genus  Uncinaria,  family  Strongv- 
lida.  Two  species,  the  Uncinaria  duodenale  and  the  Uncinaria  ameri- 
cana,  occur  in  man.  The  American  parasite  diflfers  from  the  old-world 
hook-worm  in  the  character  of  its  oral  armature  and  the  size  of  the 
ova.  The  Uncinaria  duodenalis  is  identified  by  the  fact  that  the  mouth 
possesses  two  pairs  of  hook-like  ventral  teeth  and  one  pair  of  dorsal 
teeth.  The  ova  measure  50  u  to  60  //  by  32  u.  In  the  new-world  para- 
site the  two  pairs  of  ventral  booklets  are  replaced  by  semilunar  plates 
or  Hps  and  one  pair  of  similar  dorsal  structures:  there  are  also  a  dor- 
sal, conic,  median  tooth  which  projects  into  the  buccal  cavity,  and  deep 

'This  proccrluro  is  tochnicallv  known  as  "tcasinp"  the  specimen. 

'  The  literature  of  this  subject  may  be  follnwid  from  the  Report  of  the  Com- 


2o6 


GENERAL   PATHOLOGY. 


in  the  capsule  one  pair  of  dorsal  and  one  pair  of  ventral  submedian 
lancets.^     The  ova  measure  64  //  to  76  /i  by  36  ^  to  40  fi. 

The  female  uncinaria  measures  9  mm.  to  16  mm.,  and  the  male 
7  mm.  to  9  mm.  The  head  of  the  parasite  is  bent  backward,  giving 
the  cephalic  end  the  contour  of  a  hook,  from  which  it  receives  its  name. 
The  posterior  end  of  the  female  is  conic,  that  of  the  male  flaring  or 
umbrella-like,  and  from  the  center  projects  the  sheath  containing  the 
penis.  The  eggs  when  passed  may  show  segmentation  or  contain  a 
developing  embryo  which  often  can  be  seen  moving  inside  the  shell. 
The  further  development  of  the  parasite  is  accomplished  in  moist  earth, 
in  which,  after  a  number  of  ecdyses,  it  becomes  encysted  and  ready  to 

infect  man. 

The  belief,  at  one  time 
prevailing,  that  infection  oc- 
curred almost  exclusively 
through  water,  has  been 
largely  abandoned.  The  ob- 
servations of  Looss,  corrobo- 
rated by  Claude  A.  Smith  and 
others,  have  clearly  estab- 
lished that  the  parasite  enters 
through  the  skin.  There  is  no 
doubt  that  a  papular,  vesi- 
cular, or  pustular  lesion 
(ground  itch)  may  occur  at 
the  point  of  inoculation,  al- 
though this  frequently 
escapes  observation;  it  is 
probable  that  the  parasite 
passes  by  the  circulation  to 
the  lung,  where,  on  account 
of  its  size,  the  capillaries  are 
ruptured,  and  with  the 
sputum  the  worm  is  swal- 
lowed, finally  developing  in 
the  duodenum.  The  trans- 
cutaneous infection  is  not 
the  only  way  by  which  the 
parasite  may  reach  the  intes- 
tine. .  Dirt-eaters  may  introduce  the  parasite  in  a  form  adapted  to  its 
further  development  in  the  alimentary  canal.  The  point  of  attachment 
corresponds  to  the  area  of  maximum  alkalinity  of  the  bowel  contents, 
extending  from  the  second  portion  of  the  duodenum  to  the  upper  end  of 
the  ileum.  The  number  of  parasites  present  may  be  enormous;  Ernst 
found  2768  in  the  intestine  of  a  brick-maker.  Sometimes  the  worm  is 
half  buried  in  the  intestinal  mucosa.  The  number  found  attached  at 
autopsy  is  usually  not  large.  Often  small  elevations  with  blood- 
marked  punctures  in  the  center  indicate  the  points  from  which  the 
parasites  have  become  loosened. 

The  lesions  produced  by  the  uncinaria  may  be  brought  about  partly 

'  Report  of  the  Commission  for  the  Study  and  Treatment  of  Anemia  in  Porto 
Rico,  San  Juan,  Dec.   i,   1904,  p.  29. 


Fig.  122. — Duodenum  showing   Attached  Uncinari.e. 
A,  A.  Papilla-like   elevations  with  central  depressions  resulting 
from   detachment   of   parasites.     (Specimen   presented   to 
the  Museum  of  the  Jefferson  Medical  College  by  Capt.  C. 
F.  Kieffer,  U.  S.  A.) 


ANIMAL    I'AKASITKS   AS  CAfSKS  Ol-    DISEASE. 


207 


l)\  the  loss  of  blood  induced  throuj^h  tin.'  wounding  of  the  <luodenum. 
partly  by  the  associated  intlamniatory  processes,  which  may  not  he 
marked,  and  possiljly,  to  a  certain  extent,  by  the  absorjjtion  of  meta- 
boHc  products  elaborated  by  the  parasite.  Allen  J.  Smith  and  Loeb 
have  shown  that  the  uncinaria  of  the  dog  protluces  a  hemolytic  poison, 
and  it  is  probable  that  some  similar  toxic  substance  is  elaborated  by  the 
hook-worms  in  man.  Ordinarily  the  amount  of  blood  extracted  can 
not  be  large,  although  no  doubt  the  continued  loss  of  a  small  fjuantity 
must  exert  considerable  inlluence  on  the  blood-making  tissue.  That 
more  blood  is  lost  than  is  actually  drawn  l)y  the  parasite  is  shown  by 
the  occasional  presence  of  submucous  hemorrhages  at  points  where  the 
parasites  have  been  attached ;  occasionally  these  small  blood-cysts  con- 
tain a  hook-worm.  More  or  less  fatty  degeneration  occurs  in  the  heart, 
liver, and  kidneys;  the  periphery  of  the  liver  lobules  not  uncommonly  con- 
tains an  orange-yellow  pigment,  and  there  may  be  areas  of  necrosis  sur- 
rounding the  intralobular  vein.  The  jiresence  of  fat  and  pigment  and 
the  occurrence  of  necrosis  strongly  indicate  the  action  of  some  toxic  sub- 
stance. The  hemoglobin  is 
low  (about  forty  per  cent.) 
and  the  erythrocytes  re- 
duced to  2,500,000,  al- 
though counts  of  less  than 
1,000,000  have  frequently 
been  observed.  Poikilo- 
c\'tosis,  poly chromato- 
philia,  and  nucleated  red 
cells  occur  in  marked  cases. 
Eosinophilia  is  the  most 
prominent  feature,  and 
over  two-thirds  of  the 
leukocytes  may  be  of  this 
type.  Sometimes  the 
lymphocytes  are  increased 
and  peculiar  myelocytes 
are  occasionallv  observed. 

The  polvmorphonuclear  cells  are  as  markedly  reduced  as  the  number  of 
eosinophiles  is  increased;  otherwise  the  percentage  is  not  materially 
altered. 

Filariasis  should  properly  include  all  the  morbid  conditions  due  to 
filaria,  but.  apparentlv  bv  general  consent  I  believe,  the  name  is  largely, 
if  not  exclusivelv,  restricted  to  manifestations  asscx-iated  with  the 
presence  of  tilaria  embryos  in  the  blood.  Filariosis,  better  than  hlaria.sis. 
conforms  to  the  names  given  other  i)arasitic  affections,  and  probably 
will  supplant  the  latter  term.  Two  filarial  diseases  will  be  considered.— 
one  manifested  bv  the  presence  of  embryos  in  the  circulating  blood, 
and  the  other  in  which  the  onlv  manifestation  is  a  local  one  due  to  a 
peculiarity  in  the  method  by  which  the  parent  worm  extrudes  her 
embrvos. 

The  term  Filaria  sanguinis  hominis'  is  applied  to  filaria  embryos 
that   are  found    in    the    circulating    blood.     The    parasite,  as  seen  in 

'  Important  literature  on  filariasis  is  given  by  DaCosta.  "Clinical  Hetnatol- 
ogv,"  second  edition.  1Q05.  pp.  413  to  421. 


Fig.    123. — FiLARJA   IImbrYo. —(frtim    F.   P.   Henry's  ciit) 
The  two  cmbr>os  shown  above   were  drawn  from  ?  inch  objec- 
tive; the  lower  from   i-inch  objective.     Red   blood- cells  are 
intrixlucc<l  for  comp.iri.son. 


208 


GENERAL  PATHOLOGY. 


the  blood,  is  an  actively  motile,  cylindric  body,  about  the  diameter 
of  an  erythrocyte,  0.2  mm.  to  0.3  mm.  long,  somewhat  blunted  anteriorly 
and  sharp  or  truncated  at  the  tail  end.  In  some  of  the  embr3'os  there 
is  a  refractile  V-shaped  spot  near  the  cephalic  extremity.  Manson 
suggests  that  this  is  a  rudimentary  water  vascular  system.  An  im- 
portant differentiation  between  the  filaria  is  the  now  thoroughly  estab- 
lished fact  that  in  certain  types  of  the  affection  the  embryos  are  found 
in  the  peripheral  blood  during  the  day-time  only  {Filaria  sanguinis 
hominis  ditirna),  others  are  found  at  night  (Filaria  sanguinis  hominis 
noctiirna)  and  not  in  the  day-time,  and  in  another  group  they  are  con- 
stantly present  in  the  peripheral  blood  {Filaria  sanguinis  hominis  Per- 
sians). The  following  table  by  Prout^  shows  the  resemblances  and 
important  differences  between  the  three  filarise  mentioned: 

TABLE  SHOWING  IMPORTANT' CHARACTERS  OF  THREE  EMBRYO 

PILARIS. 


F.  DIURNA. 


F.  NOCTURNA. 


F.  PERSIANS. 


Length,  . 
Breadth, , 
Sheath, .  . 
Head,  .  . 


0.0075  nmi. 
Present. 
(?) 

Tail •  Sharp. 

Body, I  Central    granular 

aggregation. 
V  spot, Present. 


0.3  mm. 

0.0075  rnm. 

Present. 

Cephalic  armature, 
six-lipped. 

Sharp. 

Ill-defined  aggre- 
gation . 

Present. 


0.23  mm. 
0.00455  mm. 
Absent. 
Papillated. 

Truncated. 
No    central 

gation. 
Absent. 


aggre- 


More  is  known  of  the  filaria  nocturna  than  of  other  members  of  the 
group.  While,  as  its  name  indicates,  it  is  found  in  the  peripheral  blood 
in  the  night-time  only,  if  the  host  changes  his  habits  and  is  active  during 
the  night,  sleeping  in  the  day-time,  the  period  of  peripheral  appearance 
of  the  parasite  is  also  perturbed  and  may  be  reversed.  The  embryo  is 
transferred  from  man  to  man  by  the  mosquito  (Culex  fatigans  and  certain 
Anopheles),  in  which  it  undergoes  important  developmental  changes. 
In  the  stomach  of  the  mosquito  the  filaria  sheds  its  sheath,  penetrates  the 
intestinal  wall,  enlarges  and  undergoes  a  further  metamorphosis,  finally 
reaching  the  labium  and  proboscis,  from  which  it  enters  the  blood  of  the 
next  individual  bitten. 

In  order  to  demonstrate  the  embryos  in  the  blood  it  is  necessary  to 
make  the  examination  at  a  time  corresponding  to  the  habits  of  the 
particular  filaria  sought.  A  fairly  large  drop  of  the  freshly  drawn  blood 
is  placed  on  the  slide  and  a  cover-glass  at  once  applied.  The  actively 
motile  embryo  is  readily  recognizable,  even  with  low  powers,  and  usu- 
ally is  observed  lashing  about  among  the  cells,  coiling  and  uncoiling  and 
sometimes  progressing  in  an  aimless  sort  of  way.  After  a  few  hours, 
and  especially  when  cooled,  the  movements  become  less  rapid,- eventually 
sluggish,  and  finally  cease.  Permanent  mounts  may  be  prepared  from 
dry  films,  fixed  for  fifteen  minutes  in  a  mixture  composed  of  equal  parts 
of  absolute  alcohol  and  ether;   after  fixation  the  spread  is  air-dried  and 

'  "Brit.  Med.  Jour.,"  Jan.  26,  1901,  p.  210.  I  have  omitted  the  column  de- 
scribing the  organism  of  which  Prout  writes. 


ANIMAL    l'AUASlli;S   AS   CAL'SKS  ( )!•    DISKASK. 


209 


stained  tor  tive  mnniles  m  a  one  per  cent,  atjueous  solution  of  thionin; 
wash  in  water,  dry,  and  mount  in  balsam.  The  stains  devised  by  Leish- 
man,  Jenner,  and  Wright'  may  be  used,  but  give  less  satisfactory  results. 
The  adult  parasite  producing  the  embryo  of  the  Filaria  sanguinis 
hominis  nocturna  is  called  the  I'ilaria  baiurofli,  antl  inhabits  the 
lymphatics  of  the  trunk — particularly  of  the  abdomen—  and  occasion- 
allv  the  extremities.  Sometimes  a  number  (six  or  seven)  of  the  adult 
worms  occur  together.  The  parasite  may  be  in  the  lymphatics  of  the 
scrotum,  inguinal  region,  or  retroperitoneal  lymph-vessels.  Although 
the  embryos  circulating  in  the  blood^estimated  by  Manson  to  number 
40,000,000  or  50,000,000 — give  rise  to  no  important  pathologic  process, 
there  are  a  number  of  more  or  less  grave  conditions  resulting  from  the 
Ivmph  stasis  and  inflammatory  phenomena  induced  by  the  presence 
of  the  ]iarent  worm  in  the  lympli- vessels.      The  l^laria  bancrofti  is  a 


Fig.  124.— Sectio.n  of  Head  of  Mosqiito  showing  Filaria  in  Position  to  be  I.soculated  during  the 
Act  of  Biting. — (From  Htru.'ard,  ajler  Matisoii.) 


hair-like  parasite  i  mm.  to  2  mm.  in  diameter  and  sometimes  attaining 
I  meter  in  length.  As  is  usual  with  parasites,  the  male  is  the  smaller. 
The  lesions  produced  by  the  adult  worm  are  grouped  under  the  names 
elejjhantiasis  and  elephantoid  disease. 

Elephantiasis  usually  affects  either  the  lower  extremities  or  the  scro- 
tum. It  is  commonly  preceded  by  lymphangitis,  which  is  followed  by  a 
gradually  evolved,  but  eventually  enonnous.  hyperplasia  of  the  con- 
nective tissues.  Manson  l)elieves  that  the  extensive  lymphatic  ob- 
struction and  connective-tissue  overgrowth  are  due  to  the  premature 
escape  of  ova  into  the  Ivmph-spaces.  The  extent  of  the  connective- 
tissue  hyperplasia  mav  be  indicated  by  the  fact  that  the  scrotum  may 
attain  a' weight  of  200  pounds,  and  the  ]r^  nt  the  ralf  may  measure  24 
to  30  inches  in  circumference. 

'See  Chapter  I.  Part  III:  Techmc  -A  Hl'>'i  i-.\.imiii.iti..ii. 


2IO  GENERAL  PATHOLOGY. 

Manson  considers  chyluria,  varicose  inguinal  glands,  lymph  scrotum, 
and  chylocele  as  elephantoid  diseases.  The  first  of  these  (chyluria)  is 
characterized  by  a  milky  white  or  pinkish  urine  which  may  contain 
coagula  or  undergo  spontaneous  coagulation,  so  that  if  the  urine  be 
passed  into  a  glass,  the  latter  may  be  inverted  without  spilling  the 
contents.  In  some  cases  the  urine  also  contains  blood — hematochyluria. 
Varicose  inguinal  glands  are  manifested  by  a  lobulated  enlarge- 
ment near  the  base  of  Scarpa's  triangle.  In  lymph  scrotum  a 
milky  or  pinkish  fluid  collects  in  the  connective  tissues  or  in  the  mani- 
festly varicose  lymphatics  of  the  organ.  In  chylocele  the  tunica  vagi- 
nalis contains  lymphous  fluid,  milky  or  reddish  in  color.  In  the  chylous 
urine  and  lymph  obtained  by  pricking  the  tissues  or  tapping  the  Ivmph- 


FiG.  125. — Elephantiasis  of  the  Scrotcm. 
The  mass  weighed  nearly  15  kilos  (31  pounds').     A.  Penis. 


vessels  not  infrequently  filaria  embryos  or  eggs  are  found.  Pyogenic 
infection  may  give  rise  to  suppurative  processes  in  the  lymph  scrotum, 
in  varicose  lymph-nodes,  and,  though  less  commonly,  in  the  hyperplastic 
connective  tissues  of  filarial  elephantiasis. 

Dracontiasis^  or  guinea- worm  disease  is  an  affection  due  to  the 
Filaria  medinensis  {Draciinctiliis  medinensis,  guinea-wonn) ,  of  which  the 
female  only  is  known.     Powell  has  demonstrated  that  the  period  between 

^Francis,  "Amer.  Med.,"  Oct.  26,  1901.  Powell,  "Brit.  Med.  Jour.,"  Jan. 
9,  1904^  p.  73.      Beclere,  "Soc.  med.  des  Hop.,"  July  17,  1903.     Powell,  "Trans. 


of  the  Bombay  Med.  and  Physical  Soc,"  Sept.,  190; 
Biol.,"  1904,  vol.  Ivii,  p.  76. 


Remlinger,  "C.  R.  Soc.  de 


ANIMAL   I'ARASITES   AS  CAUSES  OF   DISEASE. 


31  I 


infection  and  the  appearance  of  the  worm  is  about  one  year.  The 
female  is  about  60  cm.  to  90  cm.  in  length  and  2  mm.  in  diameter,  and 
is  commonly  solitary,  although  not  always  so.  It  is  usually  claimed  that 
the  parasites — probably  both  male  and  female — enter  with  the  food; 
only  the  female  develops.  It  penetrates  the  mucosa  anfl  eventually 
reaches  the  subcutaneous  tissues,  in  which  it  completes  its  development. 
Harrington  does  not  believe  in  the  entrance  of  the  parasite  through 
the  alimentary  canal.  He  is  of  the  opinion  that  it  is  introduced  either 
in  some  embryonic  form,  as  by  the  mosquito,  or  that  in  some  other 
way  it  gains  access  to  the  subcutaneous  tissues  directly  from  without. 
In  no  other  way  is  it  possible  to  explain  the  fact  that  over  seventy-five 
per  cent,  of  the  lesions  occur  in  the  lower  extremities,  and  the  greater 


FiC.   126. — DRACO.VnASIS,  or  GflXr.A-WORM  DiSEASF. 

A  case  of  Filaria  medincnsis  (retxirtcd  in  ".\nicriran  Mcdicim-."  <  ktoU-r  2t>.  i 
The  abscesses  and  swelling  of  both  feet  are  well  shown.  1-rom  the  left  iix^'t  ' 
seen;  this  limb  is  the  more  swollen.  But  one  worm  can  bo  soi-n  jir  .tr  i  Im.'  : 
five  worms  in  this  case;  four  are  shown.     The  patient  recovered 


>  be 
»erc 


number  below  the  knee.  During  the  period  in  which  the  parasite  is 
developing  in  the  subcutaneous  tissues  it  may  be  distinctly  palpal)le; 
finally  suppuration  ensues  and  the  worm  is  cast  off,  with  innumerable 
ova;    the    latter,  when  thrown  into  water,  penetrate  the  m 

which  further  development  occurs.     The  parasite  has  been  <■  m 

a  patient,  a  native,  and  always  a  resident,  of  Philadelphia,  but  it  is 
rare  in  this  country. 

In  filariasis  due  to  the  Filaria  sanguinis  hominis  a  moderate  in- 
crease in  the  eosinophils  is  not  uncommon.  In  dracontia?'  •'•-"•  ♦" 
forty  per  cent,  of  the  leukocytes  may  be  eosinophiles. 

Among  the  other  filaria  occasionally  observed  in  man  arc;     i  ;i.iria 


212 


GENERAL  PATHOLOGY. 


Fig.    127. — AcARUs    scabiei. 


bronchialis,   found  in  the   bronchi;  Filaria  loa   (3    cm.),   found  in  the 

conjunctiva;  Filaria  hominis  oris,  in  the  mouth,  etc. 

The  most  important  of  the  Arthropodae  affecting  man  are  the  mites 

or  ticks  belonging  to  the  Acaridae.     The  diseases  produced  by  the  mites 
are  called  Acarinoses. 

Scabies  or  itcJi  is  due  to  the  Acarus  scabiei 
{Sarcoptes  hominis  or  itch-mite).  The  female  is 
nearly  double  the  size  of  the  male,  and  can  often 
be  picked  out  of  the  furrows  found  in  the  skin 
in  cases  of  itch.  The  parasite  is  from  0.2  mm. 
to  0.5  mm.  in  length,  and  over  one-half  as  broad. 
It  possesses  four  pairs  of  legs,  two  pairs  ante- 
riorly and  two  posteriorly.  From  each  of  the 
foremost  pair  of  the  anterior  legs,  extend  delicate 
processes,  supplied  at  the  distal  end  with  discoid 
terminations  for  attaching  themselves  to  sur- 
faces; in  the  male  these  addenda  are  on  the 
hindermost  pair.  The  other  legs  end  in  bristles. 
The  posterior  border  is  marginated  by  a  num- 
ber of  bristle-like  hairs;  similar  hairs  are  seen 
on  the  rounded  head  of  the  mite. 

The  parasite  burrows  into  the 'epidermis,  in 

which  it  forms  cavernous  systems  attended  with  inflammation  of  the 

adjacent  Malpighian  layer.     In  the  cuticular  caverns  the  female  deposits 

her  eggs,  which  hatch 

into     young     mites. 

These    burrow,    shed 

their  external  coatings, 

and  repeat  the  process 

of    reproduction    of 

kind. 

Leptus  autumnalis, 

or    harvest-mite    (larva 

of  trombidae),  is  a  red- 
colored  parasite  de- 
posited upon  the  skin 

from  grass,  bushes,  and 

certain  cereals;  it  in- 
duces inflammation  by 

its  bite  and  by  boring 

into  the  epidermis. 
Pentastoma     denti- 

culatum  is  the  juvenile 

form  of  the  Pentastoma 

tasnioides.    The  mature 

female    is    50    mm.   to 

125  mm.  in  length  and 

6  mm.  to  10  mm.  broad; 

the    male    is     much 

smaller — 15  mm.  to  25 

mm.  long  and  2  mm.  to  5  mm.  in  breadth.     The  larva  is  between  3  mm. 

and  5  mm.  in  length,  and  is  from  i  mm.  to  2  mm.  wide — an  egg-shaped 


.m 


Fig.  128. — Scabies. 
Section  of  skin  showing  burrows  in  the  upper  layer  of  the  epidermis  (a), 
containing  female  itch  mite  (</),  ova  (f),  and  excreta  of  the  parasite 
lying  in   the  burrow  (/).     a.    Horny    layer,     b.  Malpighian    layer. 
c.  Infiltrated    cutis. — (Ziegler.) 


ANIMAL    PAKASITKS   AS  CAUSES   OF   DISKASE.  J  I  !, 

mass  occasionally  found  in  the  viscera.     The  mature  worm  is  found  in  the 
frontal,  nasal,  and  maxillary  sinuses  of  some  of  the  domestic  animals. 

The  Demodex,  or  Acarus  folliculorum  hominis,  inhabits  the  ducts 
of  sebaceous  glands  and  occasionally  ihc  hair-tollirles.  It  is  broad  just 
back  of  the  heatl,  from  which  point  it  tapers  down  to  a  blunt  hintler 
extremity;  at  the  broadest  part  are  four  short,  thick  legs.  The  length 
of  the  acarus  varies  greatly, — between  0.5  mm.  and  i  mm., — and  the 
parasite  is  usually  about  one-tenth  as  broad  at  the  widest  point. 

Ixodes  ricinus,  or  icood-tick,  inhabits  decaying  wood  in  dr>'  places 
(dry  rot  of  timber),  from  which  it  attaches  itself  to  dogs,  and  occa- 
sionally to  man.  The  head  is  black  or  brownish,  and  sup[)lied  with  a  bor- 
ing disc,  which  penetrates  the  skin,  and  through  which  the  parasite 
sucks  blood. 

The  Insecta. — The  important  insects  attacking  man  are  lice,  fleas, 
mos<iuitos,  and  flies. 

Pediculus  capitis,  pediculus  ordinarius,  licad-louse  or  common  louse, 
inhabits  the  hairy  scalp.  The  adult  parasite  is  about  i  mm.  to  2  mm. 
in  length,  and,  pathologically,  is  an  epizoon,  securing  nourishment  by 
attacks  upon  the  skin.  The  irritation  produced  l)y  the  bites  is  some- 
times followed  by  inflammation,  which  may 
be  eczematous  in  character.  The  eggs  are 
oval,  with  slightly  flattened  ends,  and  are 
attached  to  the  hair  by  a  chitinous  cement, 
which  also  covers  them.  An  egg  hatches 
out  in  from  seven  to  ten  da\"s. 

Pediculus  vestimenti,  Pediculus  corporis 
humanus,  clotJics-loiisc  or  body-louse,  inhabits 
the  clothing,  in  which  it  deposits  its  eggs. 
The  fully  developed  parasite  is  considerablv 
larger  than  the  head-louse.  From  the  cloth-  F'°-  .a^-PED.cmfs  Pre,., 
ing   the    parasite    makes    incursions  to  the 

skin,  from  which   it  obtains  nourishment.     The  bites  induce  changes 
similar  to  those  of  the  head-louse. 

Pediculus  pubis,  Pediculus  inguinalis,  Phthirius  pubis  or  inguinahs, 
or  crab-louse,  infests  the  hairv  jmbis.  axilla,  and,  rarely,  the  beard  and 
eyebrows.  The  parasite  is  smaller  than  either  the  head-louse  or  body- 
louse.     Its  habits  are  practically  the  same  as  those  of  the  head-louse. 

Cimex  lectularia,  Cimex  hirundinis,  or  bedbug,  dwells  in  beds,  floors, 
and  cracks  of  woodwork,  from  which  it  invades  the  skin,  the  bites  pro- 
ducing slight  inflammatory  lesions.  The  adult  cimex  is  3  mm.  to  6  mm. 
in  length;  the  eggs  are  laid  lietween  the  months  of  April  and  October. 
and  require  eleven  weeks  to  hatch  and  develop  the  mature  parasite. 

Pulex  irritans,  Pulex  hominis,  or  human  jlea;  the  Pulex  serraticeps, 
Pulex  felis,  Pulex  canis,  or  c/c-.i;  jlca.  The  two  parasites  closely  resemble 
each  other,  and  bv  some  are  held  to  be  identical.  They  infest  the  hair 
of  the  dog  and  cat,  from  these  animals  wandering  to  man.  Closely 
related  to  these  is  the  sand -flea,  Pulex  minimus  cutem  penetrans,  or 
Pulex  penetrans,  an  exceedingly  annoying  parasite,  smaller  than  cither 
of  the  foregoing,  and  found  in  the  sandy  areas  of  the  tropics  and  sub- 
tropics.  •  -        •     u  ♦k 

Mosquitos  or  .CMa/5.  occupying  an  important  position  in  human  patn- 
ologv,  belong  to  subdivisions  of  the  parasitic  genera  known  as  the  Culex. 


214  GENERAL  PATHOLOGY, 


Anopheles,  and  Stegomyia.  The  local  lesions  induced  by  the  bites  of 
these  parasites,  while  not  wholly  unimportant,  are  now  considered 
of  more  significance  than  formerly.  Their  relation  to  the  spread  of 
malaria,  filarioses,  and  other  parasitic  diseases  is  discussed  elsewhere. 

Myiasis^  is  a  term  apphed  to  pathologic  conditions  in  which  the 
larvae  of  flies  are  found.  The  human  excrement  not  uncommonly 
contains  larvae  of  one  kind  or  another,  but  it  is  not  known  that  the  para- 
sites provoke  any  important  disturbance.  Maggots,  occasionally  seen 
in  dead  tissues,  and,  before  the  antiseptic  methods  of  to-day,  one  of  the 
parasites  found  in  wounds,  are  the  larval  forms  of  certain  flies.  The 
eggs  deposited  on  the  wound  surface,  dressings,  etc.,  hatch,  the  resulting 
juvenile  parasites  being  known  as  maggots.  Screw-worm  disease  is  an 
affection  seen  particularly  in  the  southern  and  southwestern  parts  of 
the  United  States.  The  structures  involved  are  the  nasal  cavity  and 
accessory  simises.  Apparently  the  parasite  never  invades  a  healthy 
nasal  cavity,  but  is  particularly  prone  to  develop  in  the  nose  or  ex- 
ternal auditory  canal  when  chronic  inflammatory  processes  have  materi- 
ally altered  the  superficial  epithelium.  From  forty  to  sixty  hours 
after  the  fly  lays  the  eggs  a  sanious  discharge  and  often  epistaxis  appear, 
followed  later  by  edema  of  the  face  and  eyelids.  The  fully  formed  larva 
is  white,  lo  mm.  to  12  mm.  long,  2  mm.  to  3  mm.  wide.  Robertson^ 
reports  a  case  in  which  there  were  120  worms.  When  unrelieved,  the 
patients  frequently  die. 

Insects  and  Gommunicable  Diseases. — Recent  studies  in  communi- 
cable diseases  have  shown  that  certain  insects  are  essential  to  the  propa- 
gation of  some  maladies,  and  incidentally  are  of  importance  in  others. 
In  malaria  (see  p.  188)  the  mosquito  is  certainly  the  most  important 
if  not  the  only  means  by  which  the  disease  is  spread;  in  this  affection 
the  sexual  cycle  of  the  Plasmodium  malarias  occurs  in  infected  mos- 
quitos.  Originally  suggested  by  Finlay,  and  later  established  by  the 
experiments  of  Reed,  Carroll,  and  Agramonte,  it  is  generally  conceded 
that  the  mosquito  is  necessary  to  the  propagation  of  yellow  fever,  the 
immediate  cause  of  which  is  not  known.  In  malaria  and  filariosis  the 
animal  parasites  undergo  definite  cycles  of  evolution  in  the  interior 
of  the  insect.  In  trypanosomiasis  the  tsetse-fly  inoculates  the  disease 
from  animal  to  animal,  but,  so  far  as  at  present  known,  the  flagellate 
parasite  has  no  definite  cycle  within  the  insect.  In  another  group  of 
diseases,  including  cholera,  typhoid,  tuberculosis,  and  infections  of  the 
types  indicated,  the  germ  causing  the  disease  may  be  deposited  upon 
the  food,  and  in  that  and  similar  ways  be  conveyed  from  sources  of 
infection  to  the  healthy.^ 

'  "Exhaustive  Contribution  to  the  Study  of  Insect  Fauna  in  Human  Excre- 
ment," by  Howard,  "Proc.  of  the  Washington  Acad,  of  Sciences,"  Dec.  28,  1900, 
P-  541. 

-"Laryngoscope,"  March,  1898. 

2  Engelmann,  "Medicine,"  June,  1903,  p.  431.  Hayward,  "N.  Y.  Med.  Jour.," 
Oct.  I,  1904.  Carter,  "Med.  Record,"  May  14,  1904,  p.  761.  Austen,  "Jour,  of 
the  Royal  Army  Med.  Corps,"  June,  1904,  p.  651.  v.  Holub,  "Centralbl.  f.  Bak- 
ter.,"  Bd.  xxx,  p.  384.  Lord,  "Boston  Med.  ^and  Surg.  Jour.,"  Dec.  15,  1904. 
Nuttall,  "Epidemiological  Soc.  of  London,"  Dec.  9,  1904.  Albert,  "N.  Y.  Med. 
Jour.,"  Feb.  4,  1905,  p.  220.  Herzog,  "Amer.  Jour,  of  the  Med.  Sci.,"  March,  1905, 
P-  504- 


(MIAPTI.R  \1I. 

HYPERTROPHY,    HYPERPLASIA,    METAPLASIA,    HETEROPLASIA, 
ATROPHY,    HYPOPLASIA,    AGENESIS    OR    APLASIA. 

Hypertrophy  may  be  detined  as  increased  functional  power  having 
a  tendency  to  persist,  and  that  is  beyond  the  normal  for  a  given  tissue 
under  its  existing  conditions;  thus,  a  heart  weighing  twelve  ounces 
may  be  normal  for  the  adult,  but  would  be  hypertrophic  in  a  child. 
Hypertrophy  is  not  simply  increased  size:  c.  g.,  the  amyloid  liver  may 
weigh  six  kilos  and  be  functionally  inactive.  The  foregoing  definition 
also  excludes  tumors,  which  perform  no  useful  function.  Hypertrophy 
is  usually  associated  with  al)normal  size  and  weight,  but  the  reverse  is 
not  necessarily  true.  Many  clinicians  and  pathologists  teach  that  hyper- 
trophy is  essentially  a  structural  alteration;  in  other  words,  that  it  is 
simply  an  increase  in  all  the  elements  entering  into  the  formation  of 
an  organ  or  tissue,  each  element  retaining  its  normal  relation  to  the 
associated  structures.  It  is  to  be  granted  that  this  is  true,  but  a  defi- 
nition, or  even  the  idea  of  hypertrophy,  based  simply  upon  this  fact 
alone,  must  of  necessity  be  erroneous.  Occasionally,  one  finds  a  tumor  of 
the  mammary  gland  that  structurally  can  not  be  differentiated  from  the 
normal  gland.  The  glandular  elements  are  exactly  like  those  normally 
present,  but  the  mass  is  surrounded  by  a  capsule  and  is  sharply  differen- 
tiated from  the  normal  mamma.  The  normal  gland  being  called  upon 
for  the  manifestation  of  its  associated  functions,  will  hypertrophy, 
while  the  tumor  mass  may  or  may  not  show  any  such  enlargement. 
It  certainly  produces  no  milk,  nor  are  its  false  ducts  and  imitative 
acini  connected  with  the  normal  structures.  It  is  a  new  growth — 
something  situated  in  the  mammary  gland,  but  having  no  more  con- 
nection with  the  functions  of  that  structure  than  if  it  were  located 
eleswhere  in  the  economy.  The  continued  power  to  do  more  work 
than  normal  implies,  and  is  nearly  always  associated  with,  an  increase 
of  the  tissue  performing  the  function;  but  this  does  not  alter  the  fact 
that  the  essential  feature  of  hypertrophy  is  power  to  accomplish  more 
work  than  the  normal  organ.'  White'  proposes  the  term  hyperergia 
to  be  apphed  to  those  conditions  in  which  function  is  increased.  Hyper- 
trophy must  be  differentiated  from  the  so-called  reserve  force  of  organs  ; 
thus,  the  heart,  during  a  period  of  intense  excitement,  may  perform 
effectually  two  or  three  times  the  work  that  is  nomial  for  it,  and  still 
the  organ  may  not  be  hypertrophied.  The  condition,  however,  does  not 
persist;  it  is  temporary. 

Causes   of   H ypcrtrcphy.-— Increased    work    with    supplied    nutrition 
are  the  causes  most  active  in  extrauterine  life.     Examples  of  :• 
work  with  supplied  nutrition,  followed  by  hypertrophy,  are  a' 
The  most  familiar  instance,  and  the  one  most  often  cited,  is  the  hyper- 

'  "Lancet."  March  9.  1961. 

2I> 


2l6 


GENERAL  PATHOLOGY, 


trophy  of  the^ieart  that  occurs  as  a  result  of  alterations  in  the  valves 
or  orifices,  thereby  increasing  the  force  demanded  of  the  diseased  organ. 
Thus,  a  narrowed  aorta  or  aortic  orifice  may  require  twice  the  normal 
force  to  propel  the  blood  through  the  abnormal  obstruction.  As  an 
admirable  example  of  increased  functional  power,  the  properlv  trained 
athlete  may  be  cited.  Evidence  is  not  wanting  to  show  that,  under 
careful  and  continuous  training,  nearly  all  the  tissues  of  the  body  mav 
take  on  additional  activitv.     These,  however,  fail  to  account  for  certain 


Fig.  130. — Hypertrophy  of  the  Mamme. — (Debicrre,  Simes'  trandalion.) 

enormous  overgrowths  of  organs  or  tissues  that  occasionally  occur. 
Thus,  general  or  partial  giant  growth  may  arise  without  any  apparent 
extra  demand  for  work,  although,  of  course,  the  extra  nutrition  is  sup- 
plied. This  phenomenon  (giant  growth)  has  been  said  to  arise  from 
congenital  impulse — an  expression  that  only  moves  our  ignorance  of  the 
actual  cause  jback  to  a  period  of  which  we  knew  less  concerning  the 
functions  of  organs. 

Still  more  difficult  to  explain  are  those  remarkable  cases  of  hemi- 


IlYI'KkTKOIMIY.  217 

hypertrophy,  siuh  as  have  been  reported  1)\-  Kcisinann.'  Maikay.' 
Hutchison,^  and  many  others.  In  these  inrhvifluals  hut  one-half  of 
tlie  face  or  one-lialf  of  the  l)ody  is  materially  larj^'cr  than  the  normal. 
In  the  case  rejiortcd  by  Hutchison  some  of  the  ])aired  viscera  were 
affected;  the  left  kidney  weip^hcd  56  jrm.,  the  rij^lu  2H  j^m.;  the  left 
suprarenal  weighed  42  gm.,  and  the  right  14  gm.  The  case  reported  by 
Reismann  is  the  only  one  of  which  I  know  in  which  one-half  of  the  body 
was  enlarged  with  associated  enlargement  of  the  ojjposite  half  of  the 
cranium.  Such  a  case  strongly  suggests  that  the  central  nervous  sys- 
tem exerts  some  influence  on  the  ])cculiar  tissue  overgrowth,  and  this 
view  is  further  supjiorted  by  the  unilateral  distribution  of  the  lesion 
in  many  cases.  Further  than  this  we  have  no  information  upon  which 
to  base  a  satisfactory  ex])lanation  of  the  condition.  In  some  of  the 
cases  the  overgrowth  has  been  restricted  to  the  bone,  in  others  the  pan- 
niculus  adiposus  alone  was  involved,  while  in  still  others  all  the  tissues 
of  the  affected  part  appeared  to  participate  in  the  change. 

Since  we  have  come  to  appreciate  the  fact  that  many  organs  per- 
form functions  of  nutrition,  secretion,  heat  production,  etc.,  it  is 
conceivable  that  some  extraordinary  call  has  been  made  upon  them, 
the  nature  of  which  we  can  not  in  the  present  state  of  our  knowledge 
estimate;  this  extra  call  may  constitute  the  demand  for  additional 
tissue,  and  hence  hypertrophy.  There  can  be  no  apparent  reason  for 
an  enormous  hypertrophy  of  the  facial  and  long  bones,  as  is  sometimes 
seen;  but  there  must  be  some  reason  for  the  change,  and  whether  this 
be  attributed  to  changes  in  innervation  or  to  unusual  demand  for  some 
functional  activity  that  we  can  not  estimate  (such  as  Ijlood-making 
by  the  marrow)  remains  to  be  further  studied.  There  is  every  reason 
to  believe  that  some  forms  of  overgrowth  depend  upon  functional 
perversion  on  the  part  of  one  or  more  internal  secretions.  Wieting,* 
in  discussing  giant  growth,  calls  attention  to  the  well-known  fact  that 
disturbances  of  testicular  development  are  often  associated  with  per- 
turbations of  nutrition.  In  eunuchs  the  epiphyseal  cartilages  persist 
much  longer  than  in  normal  males.  In  the  giant  reported  by  Wicting 
the  height  was  215  cm.;  there  was  a  history  of  hereditary  syphilis  and 
the  testes  were  evidently  immature.  Exactly  what  internal  secretion 
is  produced  bv  these  organs  and  the  method  by  which  it  operates,  are 
not  known.  Akromegaly'  is  an  affection  in  which  it  is  manifest  that 
some  internal  secretion,  either  directly  or  indirectly,  is  responsible 
for  the  condition  found.  The  fact  that  the  disease  is  frequently  asso- 
ciated with  alterations  in  the  pituitary  body  or  thyroid  gland,  and 
sometimes  both,  is  suggestive. 

Whatever  may  be  the  form  in  which  hypertrophy  occurs,  two  con- 
ditions appear  to  be  essential:  (i)  The  nutrition  supplied  must  l>e 
adequate,  and  (2)  the  necessary  stimulus  for  utilizing  the  supplied 
food  is  necessary.  The  stimulus  for  growth  is  usually  l)rought  about 
by  a  slowly  advancing  demand  for  increased  work.  Resting  organs, 
no  matter  how  well  nourished,  are  not  likely  to  hypertrophy;    this  is 

"Australasian  Med.  Gazette,"  June  20,  1904. 
"Brain,"  Autumn,   igo4,  p.  3.SS. 
"Brit.   lour,  of  Children's  Di.sinscs."  June,  1904- 
"Deut.mcd.  Wwh.."  1003,  Bd.  xxix...\os.  21  and  22. 
See  Part  III.     Chapter  on  Diseases  of  the  Bones. 


2l8  GENERAL  PATHOLOGY. 

shown  in  the  well-known  fact  that  the  inactive  muscles  in  limbs  treated 
for  fracture  progressively  waste,  and  that  renewed  growth  at  once  be- 
comes evident  when  muscle  function  is  resumed.  When  hypertrophy 
is  to  be  developed  by  therapeutic  measures,  it  is  necessary  that  the 
work  thrown  upon  the  organ  must  be  gradually  and  not  suddenly  in- 
creased.    Overwork  is  invariably  followed  by  wasting. 

Hypertrophy  is  sometimes  said  to  be  true  or  false;  the  latter  is  not 
possible.  The  term  false  hypertrophy,  or  pseudohypertrophy,  is  applied 
to  large  organs  in  which  the  increase  in  size  is  not  attributable  to  in- 
creased functional  power  or  to  increase  of  the  elements  in  the  normal 
proportions,  but  rather  to  increase  in  size  due  to  the  invasion  of  the 
tissues  by  a  new  element,  overgrowth  of  some  existing  tissue,  or  some 
similar  condition.  The  enlargement  of  the  liver,  associated  with  amy- 
loid disease,  fatt}^  infiltration,  or  red  atrophy,  may  be  taken  as  types 
of  so-called  pseudohypertrophy.  The  term  is  a  poor  one,  and  should 
not  be  used. 

Hypertrophy  is  said  to  be  simple  and  numerical ;  by  the  former  is 
meant  an  increase  in  the  size  of  the  cells,  and  by  the  latter,  an  increase 
in  the  number  of  cells.  KoUiker  has  observed  that  the  unstriped  muscle- 
fiber  of  the  uterus,  at  the  end  of  gestation,  is  eleven  times  the  length 
and  four  times  the  width  of  the  normal  fiber  of  the  nonpregnant  organ. 
Hare  and  Coplin,  in  their  studies  of  the  influence  of  digitalis  on  the  car- 
diac muscle,  note  a  marked  increase  in  the  transverse  measurement  of 
the  fiber,  an  observation  supported  by  Tangl,  who  found  that  in  the 
ordinary  form  of  h^^pertrophy  of  the  heart  there  was  an  increase  in  the 
size  of  the  muscle-fibers,  which  increase  bore  a  definite  relation  to  the 
increased  weight  of  the  organ.  It  is  probable  that  in  most  instances 
of  hypertrophy  there  is  an  increase  in  the  number  of  cells  as  well  as  an 
increase  in  the  size  of  the  existing  elements,  both  old  and  new;  it  is 
not  probable,  however,  that  both  enlargement  and  increased  number 
of  cells  are  equally  marked  in  all  cases. 

Physiologic  hypertrophy  differs  from  other  forms  of  hypertrophy 
in  that  it  anticipates  the  increased  work  that  may  be  demanded  of  the 
tissue.  In  a  certain  sense  all  forms  of  hypertrophy  are  physiologic; 
hypertrophy  is  not  a  disease;  but  the  condition  referred  to  as  physio- 
logic hypertrophy  is  typified  in  the  enlargement  of  the  mammary  glands 
and  the  increase  in  muscular  power  of  the  uterus  in  anticipation  of 
lactation  and  labor.  Unlike  all  other  forms  of  hypertrophy,  this  con- 
dition apparenth'  arises  independently  of  existing  increased  work; 
as  far  as  our  knowledge  goes,  it  anticipates  such  work. 

Hypertrophy  is  said  to  be  compensatory  when  one  organ  or  tissue 
performs  the  work  of  another;  thus,  if  one  kidney  be  diseased,  the  oppo- 
site organ  may  undergo  hypertrophy;  if  one  lobe  of  the  liver  be  de- 
stroyed by  morbid  processes,  or  excised,  the  remaining  lobes  may 
increase  in  size.  The  term  compensatory  hypertrophy  is  also  used  by 
clinicians  in  another  sense:  e.  g.,  if  the  orifice  of  the  aorta  has  been 
narrowed,  thereby  demanding  more  cardiac  force,  and  if  the  heart  hy- 
pertrophies to  meet  the  new  condition,  it  compensates  for  the  abnormal 
obstruction,  and  the  hypertrophy  is  called  compensatory.  Once  such 
hypertrophy  develops,  and  later  conditions  lead  to  its  failure,  it  is  said 
that  the  compensation  has  failed;  a  like  expression  is  not  uncommonly 
used  to  indicate  a  preliminary  failure.     Compensatorv  hvpertrophv  de- 


II  \  l-l,  K  ri.AM  A        Ml.  I  AIM. AS!  A.  2iq 

velops  ^vllh  more  ccrlainty  in  the  younj^,  wliilo  in  extreme  a;,'e  the  tissues 
commonly  fail  to  rcsj^ond  to  ilemands  made  for  adilitional  work. 

When  a  tooth  has  been  extracted,  the  oi)posinj,'  tooth  becomes 
lonjTcr,  as  the  result  of  diminished  wear,  and  jjossibly  of  lessened  re- 
sistance.    This  is  sometimes  referred  to  as  a  form  of  hypertrophy. 

Limitations  of  Hypertrophy. — If  the  occurrence  of  hypertrophy 
depended  entirely  upon  the  demand  for  work,  there  would  be  no  reason 
for  its  failure  to  progress  indefinitely.  Experience,  however,  shows  that 
a  point  is  always  reached,  sooner  or  later,  when  compensation  fails,  and 
work  demanded  beyond  this  point  leads  to  wasting.  As  previously 
remarked,  the  older  the  individual,  the  earlier  this  occurs — a  fact  that 
suggests  that  the  blood-vessels  are  responsible,  to  a  certain  extent,  for 
the  arrest  of  the  process.  It  is  observed  in  athletes  that  if  a  man  has 
thoroughly  trained  early  in  life,  he  remains  competent  to  tram  into 
■•  condition"  throughout  the  major  part  of  his  days.  In  youth  the  blood- 
vessels are  more  fully  capable  of  increasing  their  carrying  capacity 
than  in  later  years — a  fact  very  well  known  of  the  arteries;  besides, 
the  conditions  favoring  hypertrophy  are  more  marked  in  intrauterine 
life  and  become  less  effectual  with  advancing  years.  It  has  been 
shown  that  antenatal  hypertrophy  of  the  kidney  is  associated  with  the 
formation  of  new  glomeruli  and  tuljules,  while  postnatal  hyy)ertrophy 
evinces  itself  only  by  an  increase  in  the  size  of  the  glomeruli  and  possibly 
in  the  length  of  the  tubules. 

Theoretically,  once  an  organ  begins  to  hypertrophy  there  is  no  reason 
for  arrest  of  the  process,  provided  the  causative  conditions  persist  or 
increase;  but  a  stage  is  eventually  reached  when  the  blood-supply  is 
no  longer  competent,  the  arteries  being  inadequate  or  unable  to  transmit 
the  demanded  additional  blood.  When  this  stage  is  reached,  not  only 
is  hypertrophy  arrested,  but,  if  the  demand  for  increased  work  be  con- 
tinued, wasting  occurs;  clinicians  recognize,  in  the  treatment  of  heart 
diseases,  that,  even  with  well-established  hypertrophy  and  good  nutri- 
tion, a  stage  is  reached  in  which  the  best  results  are  attained  by 
diminishing  the  work  to  be  done  rather  than  by  lashing  an  already 
overworked  organ  and  hoping  for  continued  hypertrophy. 

Hyperplasia  is  an  increase  in  the  connective  tissue  of  an  organ, 
either  associated  with  or  independent  of  increase  of  the  elements  upon 
which  the  functional  activity  of  the  organ  depends.  If  there  be  an 
increase  of  the  functionally  active  cells  of  the  organ,  the  increase  in  con- 
nective tissue  must  be  in  excess  of  that  which  is  normally  present,  in 
order  to  be  a  hyperplasia.  The  term  hyperplasia  is  also  applied  to 
disproportionate  increase  in  any  element  of  an  organ.  Thus,  a  new 
growth  of  bile-ducts  is  spoken  of  as  hyperplasia;  newly  developed 
gland-cells,  or  an  excess  of  one  constituent  of  an  organ  without  corre- 
sponding growth  of  the  other  elements,  is  also  called  hyperplasia. 

Metaplasia  is  the  direct  transformation  of  a  tissue  into  a  dissimilar 
tissue.  This  is  onlv  possible  of  tissues  of  the  same  type.  Different 
forms  of  epithelium'  may  change,  one  into  another,  or  one  connective 
tissue  mav  be  converted  into  another,  as  cartilage  into  bone,  or  fibrous 
or  loose  connective  tissue  into  fat.  Transposition  of  type  is  not  possible: 
epithelium  never  becomes  connective  tissue,  nor  is  connective  tissue 
ever  converted  into  epithelium.  An  ulcerative  process  in  the  trachea, 
after  cicatrization,  is  covered  bv  flat  epithelium  from  the  genetic  layers 


220  GENERAL  PATHOLOGY. 

of  adjacent  columnar  epithelium,  the  process  constituting  a  form  of 
metaplasia.  In  order  that  it  may  be  a  pure  metaplasia  there  must  be 
no  intervention  of  embryonic  tissue.  Theoretically,  such  a  thing  is 
possible;  but  whether  a  cylindric  cell  is  ever  actually  converted  into  a 
squamous  cell,  without  the  intervention  of  what  is  essentially  an  em- 
bryonic cell,  seems  somewhat  doubtful. 

Heteroplasia  implies  the  production  of  a  tissue  in  some  structure 
when  such  a  tissue,  which  may  be  perfectlv  normal  elsew^here,  is  not  a 
normal  constituent  of  the  organ  in  question.  The  development  of 
cartilage  or  bone  in  certain  glandular  structures,  such  as  the  parotid, 
ovary,  or  testicle,  constitutes  a  heteroplasia.  The  best  type  of  hetero- 
plastic tissue  is  a  tumor  of  the  typic  series.  It  will  be  observed  that 
heteroplasia  usually  implies  a  change  analogous  to  metaplasia.  Thus, 
in  the  instances  given  the  bone  or  cartilage  found  in  the  gland  must  have 
arisen  from  connective-tissue  elements  normally  present,  and,  hence, 
probably  a  part  of  the  normal  gland.  In  such  elements  the  proliferative 
change  terminating  in  the  formation  of  cartilage  or  bone  implies  meta- 
plastic capacity. 

Atrophy  is  the  reverse  of  hypertrophy,  and  hence  is  diminished 
functional  power,  which  has  a  tendency  to  persist  or  to  increase,  and 
which  is  associated  with  structural  alterations  in  the  tissue  involved. 
It  is  not  always  attended  by  diminished  size  or  weight,  as,  in  the 
condition  known  as  red  atrophy  of  the  liver,  the  organ  may  be  consider- 
ably increased  in  size.  Atrophy  is  not  an  arrest  of  development;  it  is 
an  affection  usually  occurring  in  developed  tissue,  although  an  arrest 
in  development  may  be  followed  by  atrophy  of  the  tissue  that  has 
already  developed. 

Causes. — Atrophy  may  be  physiologic:  e.  g.,  the  atrophy  of  the 
thymus  gland  shortly  after  birth,  atrophy  of  the  uterus  after  labor, 
atrophy  of  the  sexual  organs  after  the  menopause.  The  condition  may 
be  caused  by  pressure,  as  the  pressure-atrophies  of  the  liver.  As  a  result 
of  pressure  from  a  belt  or  a  corset,  a  deep  fissure  may  be  produced  in 
the  liver  tissue.  Again,  atrophy  of  the  hepatic  structures  may  follow 
pressure  brought  about  in  other  ways:  for  example,  in  red  atrophy  of 
the  liver  the  blood-stream  is  retarded  by  obstruction  to  its  onward 
flow  in  the  heart  or  lungs,  and  gradually  distends  the  hepatic  capil- 
laries, thereby  making  pressure  upon  the  surrounding  cells,  which, 
in  turn,  is  followed  by  atrophy.  (See  Red  Atrophy  of  the  Liver.)  In 
the  chronic  indurative  processes  taking  place  in  the  liver  the  newly 
formed  fibrous  tissue,  b}'  contraction,  presses  upon  the  hepatic  lobule 
and  gives  rise  to  atrophy.  (See  Atrophic  Cirrhosis  of  the  Liver.) 
Atrophy  due  to  pressure  is  further  shown  in  the  absorption  of  tissues 
as  a  result  of  the  constant  pressure  of  an  enlarging  tumor  or  aneurysm. 
Disuse  of  a  tissue  leads  to  its  gradual  atrophy.  Atrophy  from  disuse 
may  be  dependent  upon  lessened  nutrition,  as  it  is  well  known  that  the 
inactive  tissues  may  be  poorly  nourished.  This  is  the  type  of  atrophy 
that,  in  generations,  leads  to  the  disappearance  of  tissues  and  organs  no 
longer  used.  The  wasting  incident  to  the  fixation  of  a  limb  in  the  treat- 
ment of  fracture  is  in  part  due  to  its  disuse,  and  also,  in  man}'  cases, 
to  the  pressure  of  dressings.  Inanition,  or  faulty  nutrition,  whether 
general  or  local,  gives  rise  to  atrophy;  as  examples  of  general  atrophy 
due  to  inanition  may  be  mentioned  the  progressive  muscular  wasting 


ATROPHY.  22  1 

that  occurs  in  consumption,  in  the  cachexia  of  mahpnant  tumors,  and 
in  profound   blood  dyscrasias. 

In  the  atrophies  due  to  faulty  nutrition  the  cellular  elements  having 
the  most  work  to  do  usually  sutler  most.  That  this  is  not  always  the 
case,  however,  is  shown  by  the  extreme  muscular  wasting  that  occurs 
in  pulmonary  tuberculosis,  and  by  the  fact  that  the  kidney  and  liver 
mav  not,  at  the  same  time,  show  any  perceptible  lessening  in  weight 
or  in  functional  power.  The  lessened  nutrition,  upon  which  inanition 
atro])hv  depends,  must  not  be  too  suddenly  ai)])lied,  nor  must  the 
starvation  of  the  tissue  be  extreme;  as  a  result  of  either  of  the.se  con- 
ditions the  tissue  may  undergo  necrosis  rather  than  atrophy.  The  in- 
duction of  local  atrophy  by  restricted  starvation  has  been  utilized  in 
treatment;  rapidly  growing,  inoperable  tumors  have  had  their  growth 
successfully  limited — for  the  time  being,  at  least — by  ligation  of  the 
arteries  supplying  them  with  nutrition. 

Certain  atrophies  are  spoken  of  as  trophic  or  nciirqpq{]iir-  r — ^.. 
atrophy  associated  with  disease  of  the  anterior  cornu  of  the  spinal  cord ; 
unilateral  neuropathic  atrophy  of  the  face.  It  is  presumed  that  cer- 
tain elements  in  the  central  nervous  system  preside  over  nutrition,  and 
that  disease  or  injury  of  these  elements  brings  about  nutritive  changes 
in  the  tissues  over  which  they  preside;  thus,  destruction  of  the  motor 
cells  in  the  cord  is  associated  with  wasting  of  the  muscles  with  which 
the  cells  are  connected.  It  is  evident,  of  course,  that  here  we  have  to 
deal  with  a  complex  process;  in  addition  to  the  so-called  trophic  in- 
fluence of  the  cells,  it  is  necessary  to  consider  the  wasting  incident  to 
disuse  of  the  muscles  involved.  The  neuropathic  atrophies  also  include 
muscle  wasting  depending  upon  section  of  the  nerve  supplying  the 
affected  tissues,  and  upon  pressure,  tumor  infiltration,  inflammation  or 
degeneration  of  the  motor  fibers  supplying  the  muscles  that  waste. 
Edinger^  does  not  believe  that  the  restriction  of  certain  atrophies  to 
definite  groups  of  muscles  depends  upon  any  elective  qualities  possessed 
bv  the  poison,  but  rather  upon  increased  susceptibility,  largely  due  to 
the  fact  that  the  particular  muscles  affected  are  those  having  most 
work  to  perform. 

Inflammatory  processes  may  lead  to  atrophy  by  pressure  and  by 
interference  with  nutrition,  it  is  probable  that  the  .so-called  in- 
flammatory atrophies  depend  upon  the  immediate  action  of  the  irritant 
and  properly  belong  with  the  necroses  rather  than  the  atrophies. 

It  is  believed  by  some  that  certain  substances  in  the  general  circu- 
lation may  manifest  a  selective  activity  upon  given  tissues,  thereby 
leading  to'  their  atrophy  and  absorption.  Exactly  how  this  change 
is  brought  about  it  is  quite  impossible  to  say,  but  there  can  be  no  doul)t 
that  examples  apparently  coming  under  this  head  occur.  Atrophy 
of  the  thyroid  gland  during  the  administration  of  iodin  and  atrophy  of 
the  extensor  muscles  of  the  forearm  in  chronic  lead-poisoning  may  be 
cited  as  examples  of  atrophic  processes  apparently  depending  upon 
the  activity  of  ingested  bodies  or  substances  in  other  ways  introduced 
from  without. 

In  the  cells  and  tissues  involved  in  atrophy  there  is  general  shrink- 
ing of  the  diseased  structures;  the  cells  become  granular  and  not  un- 
commonly pigmented ;  it  is  reasonable  to  suppose  that  in  this  granular 
'  "Deut.  mcd.  Woch,"  1904.  N'^s-  45.  49.  and.sj;    190S.  ^'os-  '  ^"'^  ^ 


222  GENERAL  PATHOLOGY. 

or  fatty  condition  absorption  of  the  cells  is  readily  possible;  certainly, 
functional  activity  is  enormously  diminished,  if  not,  in  advanced  cases, 
suspended.  In  some  cases  the  removal  of  wasting  tissues  is  brought 
about  by  the  intervention  of  cells  partaking  of  the  nature  of  phago- 
cytes, it  has  been  shown  that  the  roots  of  the  temporary  teeth  dis- 
appear under  the  influences  of  special  cells  applied  to  the  exterior. 
Exactly  how  far  autolysis  is  operative  in  the  absorption  of  wasting 
structures  is  not  accurately  known.  Langstein  and  Neubauer^  have 
demonstrated  that,  at  the  end  of  gestation,  the  uterus  contains  an 
autolytic  substance,  and  suggest  that  it  is  through  the  activity  of  this 
body  that  involution  of  the  organ  normally  occurs. 

This  association  of  structural  change  with  absorption  and  disappear- 
ance of  cells  has  led  to  the  name  degeneration  atrophy.  It  is  probable 
that  all  atrophies  are  associated  with  some  degenerative  phenomena 
in  the  cells;  by  no  other  means  can  we  explain  the  disappearance  of 
structure.  It  is  held,  however,  that  atrophy  is  possible  without  appre- 
ciable cell  change;  such  a  condition  has  been  termed  simple  atrophy. 
Again,  the  term  simple  atrophy  is  used  to  indicate  a  diminution  in  the 
size  of  the  cells,  while  numerical  atrophy  implies  a  reduction  in  the  num- 
ber of  cells.  Gutch^  finds  that  in  brown  atrophy  of  the  heart,  when 
advanced,  the  muscle-fibers  are  conspicuously  reduced  in  size,  and  it  is 
a  common  observation  that  in  wasted  organs,  in  which  the  atrophy  is 
uncomplicated,  the  affected  cells  are  smaller  than  normal.  It  is  prob- 
able that  in  nearly  all  atrophic  processes  reduction  both  in  size  and 
number  occurs. 

When  the  atrophic  phenomena  are  due  to  the  inability  of  the  cell 
to  assimilate  supplied  nutrition,  the  lesion  is  said  to  be  an  active  atrophy; 
when  the  fault  lies  in  deficient  nutrition,  the  condition  is  called  passive 
atrophy.  The  same  cause  acting  upon  different  tissues  may  give  rise 
to  atrophy  in  some  and  not  in  others.  Again,  two  tissues,  apparently 
similarly  placed  with  regard  to  nutrition,  may  show  different  degrees  of 
atrophy,  although  the  indications  are  that  the  cause  acts  equally  upon 
the  two  elements;  thus,  the  connective  tissue  of  glands  wastes  slowly, 
while,  in  the  presence  of  the  same  causal  factors,  the  parenchymatous 
structure  may   show   a  far  more   marked   atrophic   change. 

Hypoplasia  difl'ers  from  atrophy  in  that  development  has  been 
arrested  either  before  or  after  birth;  it  is  not  wasting  of  tissue,  but 
failure  to  reach  the  normal  development.  The  process  may  involve 
the  whole  body,  or  it  may  be  restricted  to  one  or  more  organs  or  parts 
of  organs,  or  to  the  organs  belonging  to  a  single  system;  as,  for  example, 
hypoplasia  of  the  genital  apparatus.  Dwarfs  are  examples  of  hypo- 
plasia. Symptomatic  infantilism  is  applied  to  individuals  whose  growth 
has  been  stunted  by  malnutrition  or  disease.  Ateleiosis  is  a  form  of 
developmental  disorder  characterized  by  the  persistence  of  child-like 
peculiarities  in  adult  life.  Gilford^  recognizes  two  forms  of  the  affection; 
in  the  asexual  ateleiosis  the  developmental  arrest,  in  addition  to  other 
structures,  also  involves  the  sexual  organs,  which  undergo  no  further  ev- 
olution after  the  abnormality  is  inaugurated.  The  degree  of  the  arrest 
is  determined  by  the  age  at  which  it  begins.     It  may  originate  before 

^  "Miinch.  med.  Woch.,"  July  29,   1902. 
^  "Jour,  of  Path,  and  Bact.,"  June,   190 1. 
^  "Brit.  Med.  Jour.,"  Oct.  8,  1904,  p.  914. 


MYPdP  I.ASIA — AGENESIA.  223 

birth,  in  inlarn.\v  or  early  chiUlhuoil,  or  even  late  in  adolescence.  The 
sexual  organs  retain  the  characteristics  present  at  the  time  the  affection 
began;  in  one  of  Gilford's  cases  a  boy  aged  twelve  years  possessed  gen- 
erative organs  no  further  developed  than  those  of  an  infant  at  birth. 
In  this  condition  the  resemblance  to  true  infantilism  is  strong.  In  sex- 
ual ateleiosis  the  dwarfing  is  general  except  that  the  generative  organs, 
at  maturity,  are  developed  as  usual.  With  this  group  belong  some  of 
the  celebrated  dwarfs,  such  as  Tom  Thumb  and  his  wife.  Commodore 
Xutt,  Minnie  Warren,  and  others.  The  head,  limbs,  figures,  and  facial 
characters  are  those  of  childhood.  Nanism  and  nanosoma  are  terms  ap- 
plied to  dwarfs  without  any  special  consideration  as  to  the  character  of 
the  dwarfing.  Of  the  causes  of  these  and  allied  conditions  little  is  known. 
In  cretinism'  there  is  absence,  or  hypoplasia,  of  the  thyroid  gland  asso- 
ciated with  arrest  of  growth  and  other  important  nutritional  distur- 
bances; the  affection  is  amenable  to  treatment  by  thyroid  substance 
or  extract.  Cretins,  although  small  of  stature,  are  not  dwarfs  in  the 
scientific  comprehension  of  the  term,  nor  is  dwarfism  to  be  regarded 
as  a  manifestation  of  the  cretinoid  state. 

When  hypoplasia  is  not  universal  but  is  restricted  to  one  side  of  the 
bodv  or  one-half  of  an  organ,  as  tlie  brain  (some  types  of  microcephalus), 
it  is  known  as  asymmetric  hypoplasia.  The  cause  may  lie  in  incomplete 
development,  or  partial  occlusion  of  the  blood-supply  to  the  tissues 
involved.  This  not  rarely  proves  to  be  the  case  where  syphilitic  en- 
darteritis has  lessened  the  blood-supply  to  an  organ  or  a  part  of  an 
organ;  an  example  of  the  first  is  sometimes  seen  in  the  kidney,  and 
of  the  latter  in  the  liver.  The  environment  of  organs  may  lead  to  hypo- 
plasia, as  when  bands  of  inflammatory  tissue  restrict  their  growth,  or 
failure  in  the  development  of  the  skull  limits  the  increase  in  the  size  of 
the  brain.  The  growth  of  an  organ  may  be  arrested  by  destruction 
of  the  nervous  mechanism  presiding  over  its  functions.  Thus,  if  the 
ganglion  cells  in  the  anterior  cornu  of  the  spinal  cord,  in  the  area  sup- 
plving  a  member  or  parts  of  a  member,  be  destroyed  (anterior  polio- 
mvelitis)  early  in  life,  subsequent  development  of  the  affected  struc- 
ture is  interfered  with  or  absolutely  arrested.  Still  other  types  of 
hypoplasia  must  be  traced  to  fetal  anomalies.- 

Agenesia,  agenesis,  or  aplasia  should  be  restricted  to  mean  entire 
failure  ot  development:  that  there  has  Vteen  no  effort  at  the  production 
of  an  organ  or  tissue.  This  is  seen  in  the  kidney  at  times,  and  is  usually 
due  to  obliterative  disease  of  the  renal  artery.  The  term  is  also  applied 
to  the  disappearance  of  partly  developed  organs.  It  may  be  used  to 
indicate  the  failure  of  a  given  structure  of  an  organ  to  develop.  As  an 
example  of  the  latter,  occasionally  the  fibrous  skeleton  of  an  organ 
is  fully  mature  without  any  corresponding  development  of  the  paren- 
chyma, in  which  case  there  is  said  to  be  agenesis  of  the  parenchyma. 

>See  Part  III,  Diseases  of  the  Thvroid  Gland. 

'See  Achondroplasia,  Part  II,  Diseases  of  the  Osseous  System.  Also  Poncct 
and  Lereische  ("Revue  de  Chir.,"  Dec.  10.  1903,  p.  657)  and  Peloquin  (Thes^  dc 

Lvon.    T(,n?-r<>-i:     \i>     :^:). 


CHAPTER  VIII. 
INFILTRATION   AND    DEGENERATION. 

(A)  INFILTRATION. 

Infiltration  is  the  "filtering  in,"  or  deposit  in  organs,  of  some  sub- 
stance not  normally  present,  or  an  excess  in  quantity  of  a  material  that 
normally  constitutes  a  part  of  the  affected  tissue.  It  will  be  observed 
that  the  term  "infiltration"  is  here  applied  to  a  material  and  not  to  a 
tissue,  although  one  must  confess  that  the  difference  is  not  striking. 
If  tissues  are  included  as  infiltrating  bodies,  then  a  tumor  invading  an 
organ  would  be  an  infiltration;  such  is  not  the  meaning  of  the  term  in 
the  sense  here  used.  The  materials  studied  in  the  infiltrations  are 
chemic  substances,  rather  than  tissues  possessing  definite  histologic 
structures.  Thus,  fat,  lime  salts,  the  various  pigments,  glycogen,  and 
even  amyloid  material,  are  bodies  with  definite  chemic  composition,  and 
not  composite  mixtures  of  many  agents,  as  are  the  tissues.  It  is  true 
that  amyloid  material  has  a  rather  characteristic  histologic  structure 
and  stain  reaction;  so  have  many  crystals,  but  this  does  not  make  them 
tissues,  in  the  common  acceptation  of  the  term.  Infiltrations  are  (i) 
fatty;  (2)  amyloid  or  albuminoid  or,  possibly  more  correctly,  larda- 
ceous;  (3)   pigmentary;  (4)   calcareous;  (5)   glycogenic. 

I.  Fatty  infiltration  consists  in  the  addition  of  fat  to  an  organ  in 
which  fat  is  not  normally  present,  or  a  notable  increase  in  the  amount 
of  fat  in  an  organ  that  normally  contains  less.  The  recent  studies 
of  Taylor,^  Shattock,-  Ribbert,^  and  Arnold^  review  in  detail  the  argu- 
ments for  and  against  recognizing  fatty  infiltration  and  fatty  degenera- 
tion as  distinct  processes.  The  tendency  to  speak  of  fatty  infiltration 
as  normal  fatty  degeneration,  and  to  regard  the  change  usually  desig- 
nated fatty  degeneration  as  an  exaggerated  manifestation  of  the  first- 
named  condition,  seems  confusing  and  offers  no  advantages  over 
previous  custom. 

Under  certain  conditions  the  deposit  of  fat  may  properly  be  con- 
sidered as  physiologic.  This  same  deposit,  however,  carried  to  excess, 
may  interfere  with  the  nutrition  and  function  of  the  involved 
or  adjacent  tissues,  and  when  this  stage  is  reached,  the  process  be- 
comes essentially  pathologic.  As  evidence  of  the  physiologic  deposit 
of  fat  one  need  but  cite  the  fat  normally  present  in  the  hepatic  cell, 
which  is  apparently  necessary  for  the  proper  functions  of  that  struc- 
ture. A  certain  amount  of  fat  is  normally  contained  in  the  subcutaneous 
tissue,  in  the  orbit,  in  the  perirenal  tissues,  and  elsewhere.     Physio- 

'  "Amer.  Jour,  of  Med.  Sci.,"  1S99,  vol.  cxvii,  p.  569. 
^  "Jour,  of  Path,  and  Bact.,"  Dec,  1903,  p.  234. 
^  "Deut.  med.  Woch.,"  vol.  xxix,  p.  44. 
'      \"Virchow's   Arch.,"    Bd.  171,  also  "Miinch.  med.  Woch.,"  Oct.  27,  1903,  p 
1857. 

224 


IN'  KILTRATIO.V   ASM)   DEGE\  ER  ATloN  . 


225 


logically,  the  fat  deposited  in  the  areas  named  may  perform  a  number 
of  functions:  the  first,  and  probably  the  most  important,  function  is  the 
storage  of  reserve  food  that  may  be  called  upon  when  the  usual  source 
of  nutrition  for  any  reason  becomes  inadequate.  The  fat  in  the  orbit 
as  well  as  that  around  the  kidney  acts  as  a  cushion,  offering  to  the 
adjacent  organ  a  certain  amount  of  protection  from  injury. 

Causes. — Increased  nutrition:  decreased  work;  slowed  circulation; 
reduced  or  faulty  oxidation.  In  increased  nutrition  fat  is  stored  in  the 
tissues  being  in  excess  of  the  quantity  that  the  cells  can  utilize  for 
existing  demands.  If  the  functional  activity  of  the  cell  be  reduced  by 
lessened  demand,  and  the  normal  amount  of  blood  is  sent  to  the  cell, 
the  nutrition  is  in  excess,  and  fattv  infiltration  may  result.     Moderate 


4 


-'^-^r-yjJr:^ 


_  I> 


f 


A 


Fig.  131. — LivKR    Showing  Cirrhosis  with  .\i>van(  n«  1  ai  •      'n 

Death  was  the  result  of  croupous  pneumonia  and.  therefore,  an  added  ({ranubr  1  cloudy  »wcllni. 

the  few  previously  unaltered  liver  cells  is  present.     A.  A.  Groups  of  Krann!  «.  Liver  ecu 

protoplasm  of  which  is  almost  completely  rcplacefl  by  f.it.     C.  Imperfectly  uuiUncd  bile-duct.     U.  forij 
branch  surrounded  by  the  newly  formed  fibrous  tissue. 


retardation  of  the  circulation  gives  rise  to  fatty  infiltration ;  thus,  slowmg 
of  the  circulation  partly  accounts  for  the  fat  intiltrated  into  the  con- 
nective tissue  of  the  omentum  and  mesentery  in  cirrhosis  of  the  liver, 
and  also  for  the  fatty  infiltration  that  occurs  in  the  liver  lobules  in  cir- 
rhosis. 

The  infiltration  of  fat  occasionally  observed  m  the  liver  in  tubercu- 
losis, and  associateil  with  marked  emaciation,  and  the  infiltration  so.-n 
in  the  subcutaneous  tissues  in  chlorosis,  where  the  blood  findings  wcuM 
certainlv  indicate  that  nutrition  is  not  in  an  ideal  condition,  are  t.i  -•  -i 
to  be  examples  of  fatty  infiltration  doT.cn.liiu'  upon  taultv  oxidati-:.. 
16 


226 


GENERAL  PATHOLOGY. 


The  origin  of  the  stored  fat  has  been  a  matter  of  much  discussion.  It 
is  now  generally  conceded  that  it  may  arise  from  a  number  of  sources. 
In  the  fatty  deposits  of  hypernutrition  it  is  usually  held  that  it  repre- 
sents the  fats  and  sugars  in  the  food,  and,  to  a  limited  extent,  the 
albuminoids.  In  deposits  from  other  sources  it  is  not  improbable  that 
the  albuminoids  are  more  important  as  sources  of  the  fat  than  the 

usual    food-products     to 
which  it  is  attributed. 

Sites. — The  cells  nor- 
mally containing  fat  as 
one  of  their  essential  con- 
stituents are  first  to  show 
excessive  deposit  of  the 
material  when  changed 
conditions  lead  to  infil- 
tration. This  is  observed 
in  the  liver,  particularly 
in  the  peripheral  zone  of 
the  liver  lobule;  in  the 
general  subcutaneous 
tissues,  with  the  excep- 
tion of  the  lax  areolar 
structures  of  the  scrotum 
and  eyelids,  and  of  the 
lips,  alae  of  the  nose  and 
ears;  in  the  connective 
tissue  between  the  mus- 
cle-fibers (pseudohyper- 
trophic muscular  paral- 
ysis, Fig.  133);  in  the 
subserous  structures ;  and 
in  other  connective 
tissues.  A  more  or  less 
circumscribed  collection 
of  fat  constitutes  a  neo- 
plasm known  as  a  lipoma 
(see  Tumors).  The  gen- 
eral infiltration  of  fat  into 
an  organ — such,  for  ex- 
ample, as  the  jheart — is 
referred  to  as  lipomatosis, 
or  adiposis,  of  the  tissue 
involved.  When  the  in- 
filtration of  fat  is  exten- 
sive, constituting  what 
might  be  termed  a  universal  lipomatosis,  the  condition  is  commonly 
spoken  of  as  obesity  or  adiposity.  Dercum  first  described  a  peculiar 
form  of  general  lipomatosis  associated  with  pain  and  other  nervous 
phenomena,  and  the  condition  is  now  generally  known  as  Dercum's 
disease.  At  first  the  fat  deposits  appear  to  be  limited,  but  later  may 
become  extensive.  The  affected  areas  are  tender  and  there  is  tender- 
ness over  the  nerve-trunks.     Some  of  the  muscles  inav  give  the  reac- 


mi^^i 


^s- 


"V 


Fig.  132. — Heart,  Extreme  Fatty  Infiltration. 
A.  Endocardium.  B.  Vein  in  myocardium.  C.  Epicardium.  D. 
Subepicardial  fat.  E.  Irregularly  distributed  through  the  myo- 
cardium from  just  above  the  leader  from  B  nearly  to  C  are  col- 
umns of  fat  as  shown  at  E.  F.  The  infiltrating  fat  separates  the 
muscle  into  irregular  bands  such  as  may  be  seen  at  i^.but  becoming 
thinner  above  and  thicker  below  this  point. 


INFM.TKATION-    AND    DEC.  K\  KR  ATIO.V. 


Muv  le-rilx 


Innitralc'l 
\  fat. 


tions  of  degeneration.       In   coiisidrralion   of  tin-    tenderness  an«l   i.ain 
Dercum  proposed  the  name  adiposis  dolorosa. 

Microscopically,  in  the  subcutaneous  and  areolar  structures,  the 
fat  is  taken  up  by  the  connective-tissue  cell;  the  nucleus  is  crowded  to 
one  side,  the  fat  existing  in  the  cell 
as  a  single  large  oil-globule;  in  the 
liver  the  fat  is  stored  in  the  hepatic 
cell.  The  nuclei  of  the  infiltrated  cells 
are  not  diseased,  but  displaced  to  one 
side,  the  "signet-ring"  appearance.  In 
the  muscles  the  fat  is  iniiltrated  be- 
tween, and  not  into,  the  muscle-tibers, 
a  condition  easily  difterentiating  fatty 
infiltration  from  fatty  degeneration.  It 
is  not  intended  to  imply  that  fatty 
infiltration  is  always  essentially  a  sim- 
ple process;  not  uncommonly  it  is 
combined  with  an  associated  fatty 
degeneration,  the  two  conditions  being 
so  intermingled  as  to  lead  many  ob- 
servers to  hold  that  they  are  essen- 
tially similar.  There  can  be  no  doubt 
that  fatty  infiltration  may  exist  inde- 
pendent of  fatty  degeneration,  and 
that    the    reverse   is   equally   possible. 

As    the    degenerative    process    is    the    graver,    the    infiltration    is    less 
important  in  the  mixeil  lesion. 

2.  Amyloid  or  albuminoid  infiltration,  also  known  as  albuminoid 
disease,  lardaceous  infiltration,  waxy  or  bacony  infiltration.  Of  the 
many    names    applied    to    this    coT-i.lit ion     tiu.    term    lardaceous    offers 


I-IG.       I.SJ.       PSEIDOHVPKRTROPHK         MlSCf- 

LAR    Paralysis;      Fatty    iNntTRAXioN 
OF  SlvscLt..-  (FliiUfrer.) 


Fig.  IJ4.  -  Universal  Lir<oMATOsis. 
From  photo^aph  tnken  at  autopsy.     The  ladavcr  weighed  540  pound*. 


certain  advantages  and  has  the  official  sanction  of  the  Royal  College 
of    Physicians;    to    avoid    the    confusion    incident    to    our    ignor.- 
in   regard    to    the  ultimate   character    of    the    processes   it   is  dec:;.«.  1 
most    wise    to    avoid    calling    it   either   an   infiltration   or   a   degener- 
ation,   and    for  |the    present   to   refer   to    it-  as   lardaceous   change   or 


228 


GENERAL  PATHOLOGY. 


lardaceous  disease.^  Amyloid  material,  or,  more  properly,  lardacein, 
is  found  during  health  in  the  prostate  gland,  and  has  been  observed 
in  the  pia  mater. 

Causes. — Amyloid  material  probably  represents  an  altered  proteid 
normally  present  in  the  blood— possibly  fibrin,  or,  more  correctly,  the 
proteid  body  or  bodies  whose  end  is  in  fibrin.  It  can  be  produced 
artificially  by  suspending  the  spinal  cord  in  alcohol  for  a  few  months. 
The  artificial  product  so  made  responds  to  the  chemic  tests  for  lardacein, 
and  can  not  be  diflierentiated  from  the  natural  material.  If  fresh  blood 
be  whipped,  and  the  fibrin  so  obtained  washed  and  treated  with  a  i :  2000 
solution  of  hydrochloric  acid,  the  mass  becomes  gelatinous,  clear,  and 
pultaceous,  and  responds  to  all   the  stains  for  amyloid  material.     As 


Fig.  135. — Liver,  Showing  Fairly  Advanced  Lardaceous  Disease;  the  Organ  Weighed  17  Pounds. 
A.  Central  vessel  of  lobule  surrounded  by  considerable  residual  liver  tissue;  the  periphery  of  the  lobule  with  cor- 
responding parts  of  adjacent  lobules  also  persists.     B,  B.  Lardacein.     C.  Interlobular  vessel. 


amyloid  infiltration  commonly  occurs  in  connection  with  long-standing 
suppuration  in  which  the  alkaline  salts  are  drained  in  excess,  and  as  the 
product  resembles  a  dealkalinized  fibrin,  it  was  supposed  that  the 
morbid  process  naturally  arose  as  a  result  of  the  removal  of  alkaline 

^  The  important  recent  literature  concerning  lardaceous  disease  will  be  found 
in,  or  may  be  traced  from  the  following  articles:  Schmidt,  "Centralbl.  f.  allg. 
Path.  u.  path.  Anat.,"  Jan.  31,  1905,  p.  49.  Monery,  "Jour.  Phys.  et  path. 
Gen.,"  Sept.  15,  1902.  Minkowski,  "Zeit.  f.  Idin.  Med.,"  1901,  Bd.  45,  Heft 
5  and  6.  Browicz,  "  Przeglad  lekarski, "  Nos.  43-44,  1901.  Litten,  "Berlin 
ichn.  Woch.,"  Dec.  17,  1900.  Green,  "Jour.  Path,  and  Bact.,"  Feb.,  1901.  Blum, 
"  Wien.  klin.  Woch.,"  March  19,  1903,  p.  349.  Godlee,  "Lancet,"  Dec.  5,  1903, 
p.  1551.  Edens,  "Zeig.  Beitr.,"  xxx,  H.  2,  1904.  Neuberg,  Ueber  Amyloid., 
*'Verhandl.  d.  Deutschen.  pathol.  Gesellsch.,"  Jahrg.  1904,  No.  i,  pp.  19-32. 


INFILTRATION   AND  DKOK  N  KR  ATIO  V. 


329 


salts  from  the  blood;  this  view  is  not  borne  out,  however,  by  the  lact  that 
lardaceous  disease  occurs  in  malaria  and  syphilis,  sometimes  unassociated 
with  suppuration.  Tuberculosis  is  often  the  cause  (50  per  cent,  ol 
the  cases),  especially  bone  and  lung  tuberculosis.  Anything  that 
greatly  reduces  the  general  nutrition  favors  its  development.  Am:'. 
the  many  careful  studies  bearing  on  the  relation  of  other  disease^  i'. 
the  occurrence  of  amyloid,  those  of  Wicht  (1S87)  and  Blum  (1903; 
merit  special  mention.  Blum's  observations  are  based  on  18,153 
autopsies,  in  279  of  which  he  found  lardaceous  disease.  Only  5  of  the 
patients  were  under  ten  years,  and  over  200  were  between  twenty  and 
fifty  years  of  age;  141  were  males.  Blum  found  that  tuberculosis  was 
the  cause  in  79.2  per  cent.;  in  Wicht's  series  59  per  cent,  were  tuber- 
culous. Wicht  traced  10  per  cent,  to  syphilis;  Blum  only  2.9  per  cent. 
Blum  made  the  interesting  observation  that  25  per  cent,  of  the  patients 
having  actinomycosis  also  have  amyloid  disease.  Practically  all  pa- 
tients with  amyloid  disease  show  more  or  less  anemia. 

By  some,  lardaceous  disease  is  regarded  as  a  degeneration.  In  a 
sense  this  is  true;  in  the  blood  the  alteration  is  of  the  nature  of  a  de- 
generation; the  material  itself  is  a  degeneration  product,  as,  probably, 
is  melanin.  As  deposited  in  organs,  it  represents  an  additional  element 
— an  infiltration;  and  as  the  degenerative  process  is  restricted  to  the 
origin  of  amyloid  material,  the  term  infiltration  is  applied  to  the  deposit 
in  organs  and  tissues.  There  is  not  adequate  proof  that,  where  found, 
it  results  from  a  degenerative  change  in  the  tissues  at  hand:  c.  i,'..  it  is 
not  probable  that  the  amyloid  liver  weighing  7  kilos  is  the  result  of  a 
degenerative  change  in  an  organ  normally  weighing  2.5  kilos.  Where- 
ever  found,  lardacein  presents  evidence  of  being  an  added  product; 
but  as  to  the  method  by  which  the  addition  is  accomplished,  we  know 
but  little.  It  may  be  that  primarily  there  is  a  deposit  of  some  body 
that  later  is  converted  into  lardacein. 

Attempts  at  the  artificial  production  of  amyloid  infiltration  bv  the 
injection  of  bacteria  or  of  bacterial  products  into  animals  have  not 
yielded  uniformly  successful  or  satisfactory  results.  Krawkow's 
experiments  were  unsatisfactory,  in  that  the  artificial  lesions  did  not 
resemble,  with  any  detail,  the  disease  as  seen  in  man.  Later  experi- 
ments by  Davidsohn  seem  to  have  been  more  successful.  Green'  has 
produced  an  amyloid  substance  by  infection  with  pure  cultures  of 
staphylococci,  but  the  results  are  not  convincing.  The  artificial  pro- 
duction of  amyloid  disease  must  be  considered,  for  the  present  at  least, 
as  being  in  the  experimental  stage. 

Sites. — The  process  usually  begins  in  the  blood-vessels,  deposition 
taking  place  in  the  intima  and  between  the  intima  and  adventitia. 
displacing,  or.  to  a  certain  extent,  replacing,  the  muscular  coat.  The 
deposit  occurs  almost  exclusively  in  the  arteriole.  l)Ut  may  be  seen 
around  the  capillaries,  and  occasionally  in  the  larger  blood-vessels. 
The  organs  most  commonly  involved  are  the  liver,  the  spleen,  the  kid- 
neys, the  blood-vessels  of  the  mucous  membranes. — more  particularly 
those  of  the  intestines.— and  the  lymph-nodes.  Of  118  cases  of  lar- 
daceous disease  observed  by  Dickinson,  the  reaction  was  present  in 
the  kidney  in  95  ;  in  the  spleen  in  76;  in  the  liver  in  65 ;  in  the  intestines 
in  35;  in  the  stomach  and  suprarenals.  each  9:  in  the  lymph-nodes 
'  "Jour,  of  Path,  and  Bact.."  Feb.,  1901. 


230  GENERAL  PATHOLOGY. 

in  5;  in  the  pancreas,  thyroid,  esophagus,  testis,  and  endocardium, 
each  I.  In  279  cases  studied  by  Blum  the  spleen  was  involved  in 
92.5  per  cent.,  the  kidney  in  81  per  cent.,  the  liver  in  62.7  per  cent., 
the  intestine  in  21  per  cent.  Godlee  is  of  the  opinion  that  when  the 
cause  of  the  disease  (for  example,  persisting  empyema)  is  removed,  com- 
plete recovery  may  occur. 

An  interesting  form  of  lardacein  deposit  is  represented  by  the  so- 
called  amyloid  tumors  which  often  arise  independently  of  wide-spread 
inflammatory  or  suppurative  processes.  These  masses  are  found  in 
the  conjunctiva,  eyehds,  lymph-nodes,  upper  air-passages,^  and  occa- 
sionally in  tumors.  Localized  lardacein  collections  may  be  found  in 
and  around  gummas.  Steinhaus^  records  a  case  in  which  amyloid  and 
hyaline  infiltrations  involved  the  myocardium  in  the  form  of  nodular 
accumulations.  Similar  nodules  occurred  in  the  submucosa  of  the 
stomach  and  intestines. 

Morbid  Anatomy. — The  amyloid  organ  is  large,  heavy,  and  pale,  the 
paleness  being  due  to  the  infiltrated  material  and  to  the  anemia;  the 
borders,  if  previously  sharp,  are  rounded;  it  is  tough  in  texture;  de- 
composition takes  place  very  slowly;  and  the  organ  possesses  a  specific 
gravity  very  much  higher  than  the  normal.  In  the  spleen  the  Mal- 
pighian  bodies  are  largely  involved,  and  usually  show  as  small  trans- 
lucent grains,  resembling  boiled  sago,  and  hence  the  name  "  sago- 
spleen."  (For  description  of  morbid  anatomy  of  lardaceous  disease 
of  the  liver,  spleen,  kidnev,  etc.,  see  chapters  on  those  organs  in  Part 
III.) 

Chemic  Tests  and  Reactions  of  Amyloid  Material. — Amyloid  material 
is  but  slightly  digested  by  pepsin,  and  only  when  presented  in  a  finely 
divided  state.  It  is  soluble  in  ammonia  and  in  strong  hydrochloric 
acid,  but  is  not  dissolved  by  dilute  mineral  acids  or  by  acetic  acid,  or  in 
saHne  solutions,  or  in  water.  The  iodin  reaction,  which  is  usually  ap- 
plied for  the  detection  of  amyloid  material,  is  obtained  as  follows:  A 
watery  solution  of  iodin,  such  as  Gram's  solution  (iodin  i  part,  potas- 
sium iodid  2  parts,  water  300  parts),  is  applied  to  the  cut  surface  of  the 
suspected  organ,  first  carefully  washing  away  any  blood  that  may  be 
present.  The  amyloid  material  is  stained  a  mahogany-brown  (see 
Plate  IV),  while  the  normal  tissue  takes  on  a  canary -yellow  color. 
If  a  small  piece  of  tissue  be  stained  with  iodin,  as  previously  directed, 
and  afterward  treated  with  a  five  to  ten  per  cent,  aqueous  solution  of 
sulphuric  acid,  the  lardaceous  material  reddens  and  eventually  turns 
blue.  Occasionally,  this  reaction  can  not  be  obtained,  the  sulphuric 
acid  deepening  the  brownish  hue  already  given  by  the  iodin.  The 
fact  that  amyloid  material  does  not  always  respond  in  exactly  the  same 
manner  has  led  to  the  belief  that  we  are  dealing  with  a  number  of  bodies 
so  closely  allied  that,  with  the  means  at  present  at  our  command,  dif- 
ferentiation is  impossible. 

For  the  histologic  demonstration  of  lardacein  the  material  should 
be  fixed  in  absolute  alcohol,  the  sections  stained  in  Gram's  solution, 
washed  in  water,  and  mounted  in  glycerin  or  glycerin  jelly.  Unfortu- 
nately, permanent  mounts  quickly  lose  the  characteristic  color.  Sec- 
tions may  be,  without  previous  staining,  dehydrated  in  a  mixture  com- 

'  See  Manasse,  "Virch.  Arch.,"  1900,  vol.  clix,  p.  117. 
^"Zeitschr.  f.  klin.  Med.,"  vol.  45,  Nos.  5  and  6. 


IM  Al 


!\ 


*^t|ll 


Cut  surface  of  spleen,  showing  lardaccous  change.  Thi 
wedge-shaiH-d  area  <ho\vs  the  iodine  reaction.  (Atlas  of  Falholof^y 
Sydenham  Society.^ 


IN'l'ILTkATIOX    AM)    UEGRNEK  ATION  .  23I 

posed  of  one  i)art  ol  tincture  ol"  iotlin  and  three  j^arts  of  absolute  alcohol, 
cleared,  and  mounted  in  oleum  oni^ani  eretici.  A  number  of  anilin  <i  • 
atl'ord  reasonably  characteristic  stams  for  amyloid  material.  Settii':i 
are  stained  in  a  one  per  cent,  solution  of  methyl-violet  for  live  minutes, 
washed  lightly  in  one  per  cent,  aqueous  solution  of  acetic  acid,  followed 
by  water  to  remove  the  excess  of  the  acid,  and  mounted  in  glycerin  or 
glycerin  jelly.  The  tissues  by  this  method  are  stained  blue  and  the 
amyloitl  material  a  reddish-violet.  lodin-green  may  be  applied  in  the 
same  manner,  although  a  longer  time  in  the  stain  is  usually  demanded ; 
with  this  reagent  the  tissue  stains  green,  the  lardacein,  reddish-violet. 
liirch-Hirschfeld  recommends  a  combination  of  gentian-violet  and 
Bismarck  brown.  Sections  are  first  stained  five  minutes  in  a  two  per 
cent,  alcoholic  solution  of  Bismarck  brown,  washed  in  alcohol  followed 
by  water,  and  this  in  turn  by  a  two  per  cent,  aqueous  solution  of  gen- 
tian violet  for  ten  minutes;  they  are  diflerentiated  in  one  per  cent. 
aqueous  solution  of  acetic  acid,  washed  in  water,  and  mounted  in  glycerin 
or  glvcerin  jelly,  or,  best,  in  levulose.  The  tissue  is  stained  brown  by 
this  method  and  the  amyloid  material  red.  Harris  recommends  the 
following  method:  Fix  material  in  alcohol,  stain  sections  three  to 
twenty-four  hours  in  carbol-toluidin-blue,  rinse  with  water,  and  mor- 
dant for  one  or  two  seconds  with  a  two  per  cent,  solution  of  ferrocyanid 
of  potassium,  wash  in  water,  and  differentiate  in  acid  alcohol.  De- 
hydrate, clear  in  cedar  oil,  mount  in  balsam.  Lardacein  is  stained 
red;  other  elements,  varying  shades  of  blue;  the  slightly  reddened 
fibrous  tissue  is  easily  identified.  In  addition  to  the  specific  staiiis 
previously  indicated,  satisfactory  exhibition  of  the  amyloid  areas  is 
afforded  by  any  good  hematoxylin  stain,  followed  by  eosin  and  mounted 
in  the  usual  manner.  vSections  so  prepared  keep  well  ami  exhibit  both 
the  normal  and  al)normal  structures  to  advantage." 

3.  Pigmentary  infiltration,-  also  known  as  pigmentation,  consist.s 
in  the  introduction  into,  or  production  by,  the  tissues  or  cells  of  pig- 
ment granules.  These  pigment  granules  may  arise  from  two  sources: 
(a)  They  may  be  imported  into  the  body,  and  are  therefore  extraneous 
pigments,  or' (6)  they  may  arise  as  the  result  of  clianges  in  elements 
nonnallv  present  in  the'  body — autochthonous  pigments.  Another 
form  of  pigmentation,  known  as  pseudomelanosis,  has  l)ecn  described; 
it  is  due  to  hvdrogen  sulphid  coming  in  contact  with  the  iron  present 
in  the  tissues  postmortem.  It  is  usually  seen  on  the  under  surface  of 
the  liver,  and  occasionally  on  the  intestines;  sometimes  the  spleen 
is  intenselv  colored.  One  aware  of  its  possible  occurrence  postmortem 
is  not  likely  to  be  mistaken,  or  fail  to  rocogni/<'  tlu-  condition  when  it 
is  present. 

'  A  very  full  bibliography  of  amyloid  disease  is  given  by  Chantemesse  and 
Podwvssots'kv,  "Les  Processus  G^n^raux, "  igoi.  p.  ao8. 

» Exhaustive  bibliography  on  Pigmentations,  see  Chanterncssc  and  Pod- 
wyssotsky,  "Les  Processus  Gcneraux,"  looi.  p.  31?.  Also  Oliver.  "Lancet." 
Nov.  14  '  190:5  p.  1245.  Tendeloo,  "MUnch.  mod.  Woch.."  Aug.  30.  1004.  P- 
1537.  HessleV  ''Amer.  Med.,"  Oct  i.  1004.  p.  .=;90-  Sehrt.  "Virch.  Arch..  '  1904. 
Bd.  177  p.  248.  von  Furth.  "Centralbl.  f.  allg^  Path.  u.  path.  Anal.."  Aug.  15. 
1904,  p.  617.  Falckenberg.  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.."  Sent..  ioo4; 
p.  662.  Parker.  "Brit.  Med.  Jour.."  Oct.  24.  1003.  p.  1052.  Osier.  "Lancet. 
Tan.  2,  1004.  p.  10.  Solman,  "Jour.  Path,  and  Bact.."  Feb..  1901.  Seattle, 
'Jour.' of  Path,  and  Bact.."  Aug..  1003.  •      '•- 


232 


GENERAL   PATHOLOGY 


(a)  External  or  Introditced  Pigments. — These  are  well  illustrated  m 
pneumoconiosis.  (See  Diseases  of  the  Mucous  Membranes  in  Part  III.) 
In  this  type  are  included  solid  pigments  arising  from  external  sources, 
such  as  hard  coal  in  miners,  iron  in  laborers  in  iron  manufactories,  and, 
in  stone  cutters,  particles  of  sand.  Any  of  these  insoluble  pigments  can 
secure  access  to  the  tissue  through  a  wound,  in  which  they  are  probably 
retained  by  the  action  of  phagocytes.  A  form  of  this  pigmentation,  as 
it  occurs  in  wounds,  is  seen  in  tattooing,  also  in  the  small  grains  of  pow- 
der that  may  be  forced  into  the  skin  in  powder  explosions. 

In  pneumoconiosis  the  foreign  material  enters  by  way  of  the  air- 
passages,  and  may  consist  of  any  solid  body  that  is  capable  of  dissemi- 
nation in  a  sufficiently  finely  divided  state  to  permit  its  inhalation. 
When  the  solid  material  is  hard  coal,  the  condition  is  spoken  of  as  an- 
thracosis  ;  when  the  material  contains  iron,  the  affection  is  known  as 
siderosis  ;  when  composed  of  sand  or  of  fragments  of  stone,  as  in  stone- 
cutters,  it  is   called  lithosis  or  chalicosis.     Potter's  pneumoconiosis— 


Fig.  136. — Section  of  Lung  Showing  Infiltration  of  the  Connective  Tissue  of  the  .-^levolar  Wall  by 
Coal-dust  (Anthracosis). — {Rindfleisch.) 


kaolinosis^results  from  the  inhalation  of  kaolin,  a  clay  used  in  the 
manufacture  of  pottery.  Dust  pigmentation  of  the  lung  also  occurs 
in  street  sweepers  and  in  the  workers  in  shoddy  mills,  granaries,  and 
other  dust  occupations.  The  inhaled  foreign  body  is  less  likely  to  give 
rise  to  important  tissue  changes  than  the  associated  bacteria  which 
accompany  it  or  later  enter  the  affected  tissues.  Of  the  inorganic  sub- 
stances, Reckzeh  holds  that  lime  is  the  least  injurious.  Dusts  of 
organic  origin,  such  as  wool  and  hair,  are  the  most  dangerous.  Once 
the  pigment  passes  through  the  protecting  membrane, — either  skin  or 
mucosa, — it  reaches  the  lymphatic  spaces,  and  may  pass  on  to  the 
lymph-nodes,  or  even  further,  eventually  reaching  the  circulation. 
A  lymph-node  may  break  into  a  blood-vessel,  and  the  solid  pig- 
ment may  be  carried  everywhere  by  the  circulation.  Weigert 
asserts  that  this  is  a  method  b}^  which  any  extraneous  pigment  reaches 
other  viscera  than  the  lung;  e.  g.,  the  liver  and  spleen.  Betz  reports 
the  case  of  a  stone-cleaner  whose  urine  suddenlv  contained  an  easilv 


INFILTRATION    AND   DEGENERATION. 


233 


sedimented  black  pigment  whicli  was  present  in  domonstrable  quanti- 
ties for  four  days.  The  carbonaceous  character  of  the  substance  was 
demonstrated  by   chemic  examination. 

Other  extraneous  pigments  do  not  enter  the  body  as  pigments, 
but  are  converted  into  pigments  by  the  action  of  the  body-juices.  Silver 
may  be  taken  as  a  type  of  these  pigments  entering  the  circulation  and 
coming  to  the  surface  of  the  body  as  an  alljuminate.  It  is  deposited  in 
the  skin  by  the  action  of  light  as  metallic  silver,  the  resulting  condition 
being  known  as  argyria. 

(b)  Pig))icnts  Derived  from  Elcmcuts  Normally  Present  in  the  Hody. — 
Pigmentation  is  a  normal  process  in  the  skin  of  the  negro,  and  in  the  iris, 
etc.     Pigments  derived  from  the  lilood — so-ca.\\ed  Iiematofienoic;  m'-o/.u/s 


?i"'^'       -■■■■■'     '^ft    '    ■  "''  ""^^"" 


^^^ 

•^  ^i^ 


M^ 


Fig.  137.— Sectki.n  of  .v  Lu.so  Showing  Chalicosis. 


P    Pleura.     ^.  Nearly  normal  air  vesicles;    some  are  slightly  emphysematous,     a.  MaM  of  infiltrated  tnatcnal 
with  dense  fibrous  capsule  and  situated  in  the  pleura,     a'.  .Similar  mass  in  the  lung  ussue^lher  n^^«*^ 


...^..  „^„.^ .  ^apsuL  „ ,  .... 

shown,     t.  Blood-ves.sel  around  a  branch  of  which  is  forming  an  area  of  inhltratioo. 
interlobular  septum. — (Schmiius^     X  30  diameters. 


i.  Thickened  fibroid. 


— are  the  results  of  changes  in  the  normal  hemoglobin  during  life.  In 
health  the  hemoglobin  is  not  yielded  to  any  of  the  tissues  with  which 
it  comes  in  contact;  in  certain  conditions,  however,  the  stroma  of  the 
erythrocvte  containing  the  normal  pigment  may  be  altered  or  destroyed 
(hemolysis),  giving  rise  to  hemoglobinemia,  or  the  liemoglobin  may  pass 
of!  with  some  of  the  excretions,  as  in  hemoglobinuria.  Dunng  life  the  two 
blood  pigments  resulting  from  changes  in  the  hemoglobin  ^rc  hematoidtn 
and  hemosiderin;  the  latter  differs  in  many  respects  from  the  former  the 
principal  difference  is  that  hemosiderin  contains  iron.  A  \' 
closelv  allied  to  those  just  mentioned  is  melanin;  with  j 
melanin  forms  the  chief  pigment  of  malaria.  Melanin  is  a  norraai  pig- 
ment in  the  skin  of  the  negro  and  around  the  nippl*^  "i  ^ho  wlute;   it  is 


•r>' 


234  GENERAL  PATHOLOGY. 

also  seen  in  tumors  .where  the  condition  is  known  as  melanosis,  or  the  tumor 
is  said  to  be  melanotic;  it  may  be  produced  by  the  cellular  activity  of 
the  part,  and  it  may  follow  hemorrhage.  In  malaria  melanin  may  be 
found  in  the  large  glandular  viscera,  such  as  the  liver,  spleen,  and  kidney, 
and  also  in  the  brain.  Rogers  has  recently  called  attention  to  a  peculiar 
pigmented  atrophy  of  the  mucous  membrane  of  the  small  intestine  in 
cases  of  malaria.  In  some  instances  the  pigment  deposit  is  sufhcient 
to  render  the  mucosa  gray  or  of  a  dark,  slaty  color. 

In  1889,  von  Recklinghausen  described  a  form  of  pigmentation  affect- 
ing a  number  of  organs  which  he  called  hemochromatosis.  Opie^  has 
very  fully  studied  the  condition  and  collated  the  literature.  Many 
glands  in  the  body  are  impregnated  with  a  reddish-yellow  or  ochre- 
colored,  granular  pigment,  containing  iron.  The  muscularis  of  the 
stomach  and  intestines  contains  a  fine,  pure  yellow,  granular,  iron-free 
pigment.  The  granules  containing  iron  are  called  hemosiderin,  the 
others  heniojuscin.  The  condition  is  associated  with  cirrhosis  of  the 
liver  and  chronic  interstitial  pancreatitis.  The  bronze  diabetes  of  the 
French  appears  to  be  a  terminal  stage  in  the  affection. 

Ochronosis"  is  characterized  by  the  deposit  of  black,  or  brownish- 
black,  iron-free  pigment  in  the  cartilages.  It  is  usually  associated  with 
melanuria.  The  source  of  the  pigment  and  the  cause  of  its  presence 
in  the  urine  remain  undetermined. 

In  Addison's  disease^  there  is  an  excess  of  pigment  in  the  rete  and 
deposits  may  also  occur  in  the  mucosa,  particularly  of  the  mouth.  The 
source  and  character  of  the  pigment  are  not  definitely  known,  although 
it  is  reasonable  to  suppose  that  it  is  a  hemoglobin  derivative. 

Jaundice.* — A  form  of  pigmentation  in  which  the  pigment  is  derived 
from  blood  coloring-matter,  but  which,  at  the  same  time,  would  not 
occur  without  the  intervention  of  another  process  in  metabolism,  is 
jaundice.  Jaundice  is  not  properly  considered  with  the  infiltrations  of 
pigment;  it  is  more  truly  the  diffusion  of  a  soluble  pigment.  Its  action, 
however,  on  many  cells  closely  resembles  that  of  insoluble  pigments. 
While  it  is  true  that  certain  blood  pigments,  including  hematoidin, 
are  chemically  identical  w4th  bilirubin,  and  that  the  latter  is  abun- 
dantly formed  when  there  is  rapid  hemolysis,  still  there  is  not  sufficient 
reason  for  believing  that  this  production  is  ever  sufficient  to  give  rise 
to  jaundice.  Bile  pigment  is  produced  in  the  liver,  and  by  reabsorption 
enters  the  circulating  blood,  and  is  the  agent  that  gives  rise  to  the  dis- 
coloration of  the  various  tissues  so  markedly  influenced  in  jaundice. 
The  pearly  white  of  the  conjunctiva  is  usually  first  to  manifest  the 
discoloration;  afterward  all  of  the  tissues  become  more  or  less  discolored. 

*  "Jour,  of  Exper.  Med.,"  vol.  iv,  1S99,  p.  27Q. 

'^  Heile,   "Virch.    Arch.,"    1900,    Bd.    clx.     Albrecht,    "Zeit.    f.    Heilkunde," 
1903,  vol.  xxiii,   Nos.    10  and   12. 
^  See  Diseases  of  the  Adrenals. 

*  Sandwith,  Cantlie,  Anderson,  and  also  Mathias.  "Brit.  Med.  Jour.,"  Sept. 
17,  1904,  pp.  672  to  678.  Anders,  "Amer.  Jour,  of  Med.  Sci.,"  April,  1903,  p.  596. 
Sacquepee,  "Arch,  de  med.  Exper.  et  d'Anat.  path.,"  July,  1902.  Jagic,  "Zieg- 
ler's  Beitrage, "  1903,  vol.  xxxiii,  p.  302.  Joannovics,  "Zeit.  f.  Heilk.,"  1904, 
vol.  XXV,  p.  25.  Pick,  "Wiener  klin.  Woch.,"  vol.  xvi,  No.  17.  Ravenna  and 
Gentili,  " Lo  Speriment.,"  Feb.,  1904.  Cocking,  "Quarterly  Med.  Jour.,"  York- 
shire, Feb.,  1903,  Eppinger,  "Beitr.  zur  path.  Anat.  u.  zur  all.  Path.,"  1903, 
vol.  xxxiii,  p.  123.  Phillips  ,"  Lancet, "  June  27,  1903,  p.  1796.  Hutchinson, 
"Practitioner,"  Feb.,   1902. 


INMLTRATION    AND   DKGENERATION, 


Commonly,  the  brain  and  spinal  cord  escape  pigmentation.  It  is 
said  that  the  gastric  and  pancreatic  secretions  do  not  sliow  the  yellow- 
ish tinge.  With  regard  to  the  sources  of  the  pigment  circulating  in 
the  blood  two  views  have  long  been  in  force,  these  leading  to  the  recog- 
nition of  two  forms  of  jaundice,  one  hepatogenous  and  the  other  hema- 
togenous. 

Hepatogenous  jaundice  depends  upon  the   production  of  bile   pig- 
ment in  the  usual  way.  and  its  al)Sorption  by  the  blood  as  a  result  of 
retention    within    the    biliary    cliannels.     This    retention    may    depend 
upon  swelling  of  the  mucous  membrane  of  the  duct,  biliary  calculi, 
tumors  within  or  without  the  duct  and  pressing  upon  it,  intlammatory 
adhesions,  kinks,  pressure  by  a  misplaced  viscus,  such  as  the  right  kid- 
ney, parasites  in  the  bile-duct,  etc.     The  resoq^tion  of  bile  as  a  result 
of  such  obvious  obstructions  as  those  just  considered  deserves  no  special 
comment.     There  are  forms  of  jaundice, however, that  arenot  obstructive 
in  the  sense  previously  indicated.     It  is  alleged  that  jaundice  may  de- 
pend upon  the  overproduction  of  bile  (polycholia);  the  abnormal  bile 
may  be  viscid,  slow-llowing,  and  hence  offer  opi)ortunities  for  resorption, 
or,  entering  the  intestine  in  large  quantities,  it  may  be  taken  up  by  the 
portal  circulation  and  returned  to  the  liver,  which  may  not  be  equal  to 
the  continued  removal  of  the  pigment  from  the  blood,  which,  escaping 
the  hepatic  cells,  passes  onward  into  the  general  circulation.     Although 
the  obstructive  origin  of  all  forms  of  jaundice  has  been  generally  accepted, 
there  has  not  been  uniform  agreement  as  to  the  route  by  which  the 
bile  elaborated  bv  the  liver  cells  enters  the   circulation.     The   recent 
studies  of  Eppinger,  Winckelmann,  Abramow.  and  Samoilowicz  indi- 
cate that  absorption  takes  place  through  the  lymphatics  of  the  liver. 
Hematogenous  jaundice  is  seen  in  connection  with  various  morbid 
processes  in  which  blood  destruction  constitutes  an  important  element. 
It  is  the  ervthrocvtolvsis  (hemolysis)  of  yellow  fever,  pyemia,  perni- 
cious malarial  fever,  and  allied  diseases  that  causes  the  form  of  jaundice 
in    question.      The   jaundice   associated   with   venom-poisoning,   phos- 
phorus-poisoning, etc..  belongs  with   this   group.     The    fortunate   pos- 
session of  an  agent  (toluvlenediamin)  destroying  the  blood  and  bringing 
about   this  form  of  jaundice   has  enabled  investigators  to  study  the 
changes  that  accompanv  the  condition.     It  has  been  shown  that  destruc- 
tion of  the  blood-cells  leads  to  the  production  of  a  bile  the  viscosity  of 
which  prevents  rapid  flow  through  the  biliar\^ capillaries,  and  hence  permits 
regurgitation,  or  at  least  increases  biliary  pressure  to  an  extent  com- 
patible with  resorption.     At  the  same  time  there  is  more  or  less  catarrhal 
swelling  of  the  mucosa  of  the  biliary  passages,  which  further  impedes 
the  flow.     The  jaundice  is  then  truly  obstructive,  and  not  actually  ot 
hematogenous  origin,  although  the  initial  step  in  the  process  was  prob- 
ably  the   ervthrocvtolvsis.      Experimental    studies    of    the    jaundice 
produced   bv  phosphorus   and    arseniureted    hydrogen  offer  conclusive 
evidence  that  the  production  is  due  to  the  same  conditions  as  toluvlene- 
diamin jaundice.     Further,  it  has  been  shown  that  if  the  liver  is  re- 
moved and  poisoning  bv  some  of  the  before-mentioned  agents  brought 
about,  blood  pigments  appear  in  the  urine,  though  bile  pigments  are 

not  found.  ,  ,  .         ,• 

A  number  of  writers  have  described  a  form  of  jaundice,  sometimes 
epidemic,    suggesting    communicability.     Such    systematic    wr,r..r^     ,<; 


236  GENERAL  PATHOLOGY. 

Strumpell,  Loomis,  and  Thompson  refer  to  it.  Pomeroy  reported  an 
epidemic  in  Calumet,  Michigan.  Costa  describes  70  cases  occurring 
among  soldiers  where  the  evidence  of  contagion  appeared  to  be  clear. 
Nicolaysen^  reports  an  epidemic  of  123  cases  and  believes  that  the  con- 
dition depends  upon  a  specific  gastro-intestinal  catarrh  transmissible 
from  person  to  person  and  often  occurring  without  its  associated  jaun- 
dice. The  infectious  jaundice  described  by  Sandwith,  the  epidemic 
catarrhal  jaundice  reported  by  Anderson,  and  the  jaundice  of  the  tropics, 
are  evidently  closely  alUed  affections.  The  relation  of  these  to  one 
another  and  to  Weil's  disease  is  not  known;  all  are  attended  by 
more  or  less  marked  jaundice,  and  hepatic  and,  usually,  splenic  enlarge- 
ment. A  number  of  bacteria  have  been  described  as  occurring  in  the 
condition,  but  no  specific  organism  has  been  isolated. 

A  pigment  closely  allied  to  hematoidin  is  lutein,  which  is  the  coloring- 
matter  of  the  yolk  of  the  egg,  and  is  found  in  the  corpus  luteum.  Lutein 
and  a  number  of  pigments  appear  to  be  rich  in  fat  and  have  been  desig- 
nated lipochromes,  placing  them  with  the  coloring-matter  of  normal 
adipose  tissue. 

There  are  a  few  pigments  that  do  not  enter  the  body  as  such,  but 
are  developed  in  the  body  from  elements  not  normally  present;  as  an 
example  of  these  may  be  mentioned  the  pigmentation  following  the  ad- 
ministration of  silver,  argyria,  to  which  reference  has  already  been  made. 

Bacterial  Pigmentation, — ^Certain  pig-ments  produced  by  bacterial 
growth  occur  in  suppuration.  The  bacillus  pyocyaneus  is  the  organ- 
ism most  commonly  producing  pigment  in  pus,  or  even  catarrhal  dis- 
charges from  such  mucous  surfaces  as  the  nose,  uterus,  and,  rarely,  the 
bowels. 

Occasionally,  the  cells  Whose  particular  function  it  may  be  to  elabo- 
rate given  pigment  fail  to  do  so.  Such  failures  often  become  as  conspicu- 
ous and  as  easily  recognizable  as  the  overproduction  of  pigment  under 
other  circumstances.  The  albino  is  an  example  of  congenital  absence 
of  pigment  production,  particularly  in  the  skin,  the  hair,  the  irides,  and 
the  choroid  coats  of  the  eyes.  A  minor  degree  of  failure  in  pigment 
formation  is  seen  in  the  condition  spoken  of  as  leukoderma,  in  which 
whitish  areas  appear  upon  a  skin  otherwise  normal.  Occasional  in- 
stances of  this  peculiar  disorder  have  been  observed  in  the  colored 
race,  the  skin  at  times  showing  areas  of  snowy  whiteness,  which  stronglv 
contrast  with  the  surrounding  normal  tissue.  No  satisfactory  explana- 
tion of  this  condition  is  at  present  forthcoming.  The  failure  in  the 
production  of  blood  pigment  seen  in  certain  blood  diseases  probably 
deserves  a  distinct  position. 

Demonstration  of  Pigment  in  Tissues. — With  the  usual  processes 
of  fixation  most  pigments  can  be  readily  recognized  within  and  between 
the  cellular  elements  of  the  structures  involved,  but  their  identification  is 
a  more  difficult  task.  The  chemic  and  microchemic  reactions  of  the 
various  pigments  are  but  poorly  understood.  In  addition  to  the  dif- 
ferentiating points  previously  indicated,  the  most  important  demon- 
stration is  that  of  iron.  As  before  stated,  hemosiderin  contains  iron; 
there  are  probably  a  number  of  pigments  included  under  the  name  of 
hemosiderin  merely  from  the  fact  that  iron  is  present.  The  demon- 
stration of  the  iron  is  usually  accomplished  as  follows:  Tissues  that 
'  "Deut.  med.  Woch.,"   1904,  vol.  xxx,  No.  24. 


I  N  1- 1  LT K  ATI O N    A  \  I)   D  K  G  E  N  K  R  AT  I  ()  N' . 

have  been  fixed  in  absolute  alcohol  arc  sectioned  in  the  usual  manner. 
Sections  are  treated  for  from  one  to  two  hours  in  a  one  per  cent,  aque- 
ous solution  of  the  ferrocyanid  of  potassium,  and  mounted  in  glycenn 
containing  0.5  per  cent,  hydrochloric  acid.  The  pijjment  contammj; 
iron,  not  in  the  so-called  concealed  or  masked  form,  will  show  the 
bright  blue  reaction.  In  order  to  secure  the  reaction  with  both  fernc 
and  ferrous  salts  it  may  be  necessary  to  use  a  mixture  of  ferrocyanid 
and  ferricyanid  of  potassium,  each  0.5  to   i   gm.  to  100  c.c.  of  water. 

4.  Calcareous  infiltration  or  calcification  consists  in  the  deposition 
in  the  tissues  of  salts  ol  lime  and  magnesium;'  the  lime  salts  are  the 
phosphate,  carbonate,  chlorid,  and  tluond;  the  magnesium  salt  is  a 
phosphate. 

The  term  petrification  ur  petrifaction  has  been  applied  to  deposits 
composed  ])urely  of  magnesium  and  other  than  lime  salts,  while  the 
term  calcification  has  been  restricted  to  lime  salts.  That  so  sharp  a 
differentiation  is  advisable  or  even  possible  is.  in  the  opinion  of  th*- 
writer,  doubtful. 

Causes. — Calcification  is  practically  never  a  ])rimary  process;  most 
frequently  it  is  secondary  to  some  destructive  change  in  the  cellular 
elements  of  the  area  involved:  e.g.,  local  changes  in  nutrition,  coagu- 
lation of  albumin,  slowing  of  the  circulation,  inflammation,  necrosis,  and 
chronic  infections.  It  may  be  said,  in' a  general  way,  that  calcification 
is  an  evidence  of  age,  and  that  the  more  marked  the  calcification,  the 
older  must  be  the  involved  tissue.  Calcification  is  one  of  nature's 
methods  of  limiting  infection,  as  is  shown  by  the  calcareous  masses 
that  collect  around  tuberculous  areas  and  in  actinomycotic  masses  and 
in  the  fungus  itself.  Thomassen-  has  shown  that,  in  animals  immun- 
ized to  the  tubercle  bacillus,  the  greater  the  immunity,  the  more  marked 
the  calcific  deposit  in  areas  containing  the  tubercle  bacillus.  The 
ultimate  cause  of  the  deposit  of  lime  salts  may  be  said  to  be  unknown. 
The  fact  that  it  is  more  or  less  constantly  associated  with  tissue  death, 
or  senescence,  would  indicate  that  disorganization  or  dissolution  of 
proteid  bodies  favors  the  deposit;  for  this  reason  it  has  been  held  that 
the  tissue  elements  in  process  of  disorganization  enter  into  chemic 
combination  and  retain  within  them  the  earthy  salts,  which,  under 
normal  conditions,  escape  or  remain  in  solution.  In  that  lorm  of 
tissue  death,  called  fat  necrosis,  often  associated  with  disease  of  the 
pancreas,  the  afTected  structures  are  promptly  infiltrated  by  calcific 
matter.  It  is  commonly  held  that  the  change  is  brought  about  by 
combination  of  the  fatty  acids  with  lime  salts  derived  from  the  circu- 
lating blood. 

Morbid  Anatomy. — The  lime  salts  may  form  distinct  concretions, 
as  in  tuberculous  abscesses  and  tuberculous  glands,  or  they  may  be  dif- 
fused between  or  into  the  cellular  elements  of  a  tissue :  c.  jj. .  the  carti- 
lages of  the  ribs.  This  latter  process  is  analogous  to  ossification  ob- 
served in  bone;  calcification  differs  from  ossification  in  that  the  former 
does  not  possess  anv  distinct  histologic  structure. 

Calcification  is  'obser\'ed  in  "healed-in"  infectious  processes,  or 
where  attempts  at  "healing  in"  have  been  made;  it  also  occurs  in  the 

'  A  full  Inblioj^raphy  of  this  subject  will  be  found  in  Chantemessc  and  Pc-^i 
wyssotsky,  "  Lcs  Processus  Generaux.  "1901,  pp.  363  to  368. 
'  "  Rev.  med.  Vet.."  1903.  vol.  x,  p.  5. 


238  GENERAL  PATHOLOGY. 

cartilages:  e.  g.,  those  of  the  ribs,  and  is  frequently  present  in  cica- 
tricial tissues,  particularly  in  those  connected  with  the  periosteum;  it 
is  seen  in  certain  tumors, — e.  g.,  psammoma  of  the  brain, — in  thrombi, 
and  in  areas  that  have  undergone  hyaline,  fatty,  and  possibly  other 
degenerative  and  necrotic  changes.  The  salts  may  be  deposited  both 
within  and  between  the  cells.  Deposit  within  the  cells  is  met  with  in 
the  ganglion  cells  of  senescence,  but  elsewhere  the  calcium  salts  are 
most  commonly  between  the  cells:  that  is,  in  the  intercellular  sub- 
stance. Calcification  following  attempts  at  repair  is  observed  secondary 
to  inflammation  of  serous  membranes,  notably  of  the  pleura  and  peri- 
cardium. It  occurs  as  a  sequence  of  inflammatory  and  degenerative 
processes  in  the  blood-vessels,  particularly  the  arteries,  and  is  also 
seen  around  the  cardiac  orifices  and  in  the  older  sclerotic  areas  in  valve 
leaflets.  A  few  remarkable  cases  of  extensive  calcareous  infiltration  of 
one  or  more  of  the  internal  organs  have  been  recorded.  The  lungs 
may  be  sprinkled  with  calcific  areas  and  ten  to  fifteen  per  cent,  of  the 
organ  may  be  earthy  matter.  Similar  miliary  calcification  is  occasion- 
ally observed  in  the  liver  and  spleen.  Sometimes  the  tendon  of  the 
diaphragm  is  affected  and  large,  calcareous  plaques  may  be  found  in 
the  mediastinum.  In  most  of  these  cases,  at  autopsy,  it  is  impossible 
to  say  exactly  what  was  the  primary  lesion  in  which  the  lime  salts 
were  deposited.  Tuberculosis  at  once  suggests  itself,  but  often  no 
evidence  in  support  of  this  view  can  be  discovered.  One  of  the  re- 
markable instances  of  calcific  deposit  is  that  occasionally  seen  in  the 
dead  fetus  of  a  ruptured  ectopic  gestation.  In  the  course  of  years  a 
fetus  remaining  in  the  abdominal  cavity  may  be  extensively  infiltrated 
with  lime  salts,  thereby  producing  a  body  spoken  of  as  a  lithopedion. 
Haultain^  has  recorded  an  instance  in  which  a  lithopedion  was  present 
in  the  abdominal  cavity  for  forty-one  years;  the  conformation  of 
the  fetus  was  so  perfectly  preserved  that  the  projecting  finger-nails 
could  easily  be  identified.  Calcification  of  the  placenta  is  occasionally 
observed. 

The  demonstration  of  calcific  deposits  does  not  commonly  require 
aid  other  than  the  gross  examination.  The  deposits  are  usually 
sufficiently  well  marked  to  be  readily  recognized  by  palpation,  and 
may  be  further  shown  by  the  occurrence  of  fracture  on  bending — a 
test  particularly  applicable  to  blood-vessels  and  valve  leaflets.  In 
sections,  the  calcific  deposit  is  not  uncommonly  first  discovered  by 
the  nicking  of  the  microtome  knife.  When  the  deposit  is  scanty,  the 
fine  granules  or  grosser  collections  may  be  readily  recognized  under 
the  microscope.  The  strong  affinity  of  the  salts  for  hematoxylin  also 
constitutes  an  important  test.  The  application  of  a  five  per  cent, 
aqueous  solution  of  hydrochloric  or  nitric  acid  leads  to  their  disap- 
pearance, the  carbonates  effervescing  as  a  result  of  the  liberation  of 
the  carbon  dioxid.  The  demonstration  of  lime  salts  may  be  further 
made  by  the  addition  of  sulphuric  acid,  which  leads  to  the  formation 
of  g\^psum  (sulphate  of  lime),  which  may  be  recognized  as  needle-like 
crystals. 

Uric  Acid  Deposits.- — With  gout  is  associated  the  abundant  deposit 

^  "Jour,  of  Obstetrics  of  the  British  Empire,"  Oct.,  1904. 

^  For  recent  interesting  review  of  the  various  theories  concerning  gout,  see 
"Practitioner,"  Juh',  1903,  vol.  Ixxi,  No.  i,  pp.  i  to  106.  Watson,  "Lancet," 
Feb.  II,  1905,  p.  347- 


INriLTkATlO.V    ANM)  DKCENKkATIoN 

of  uric  acid  and  its  salts,  particularly  in  articular  aii<i  ip;ira-.tn:.  ui.n 
structures,  although  the  kidneys,  skin,  and  tibrous  tissues  of  the  bodv 
are  also  likely  to  be  involved.     Wherever  the  deposit  takes  i  "  rc 

is  usually  a  surrounding  area  of  local  necrosis,  or  at  least  n.  c- 

generative  changes.  The  cause  of  the  deposits  has  not  been  <lchiuLcly 
determined.  We  do  not  even  know  wliether  it  is  defective  excretion, 
overproduction,  or  faulty  oxidation.  The  deposition  is  frequently 
associated  with  local  pain  and  inflammation.  The  statement  commonly 
made  that  the  deposits  consist  of  sodium  urate  is  not  strictly  true. 
as  Roberts  has  satisfactorily  demonstrated  that  they  consist  of 
sodium  biurate,  probably  precipitated,  in  the  tissues  involved,  from  the 
quadriurate  circulating  in  the  blood.  The  uratic  deposit  in  the  cor- 
tex of  the  kidney  is  irregularly  distributed,  while  in  the  medullary  por- 
tion it  follows  the  course  of  the  straight  vessels.  The  tophi  in  the  car- 
tilaginous external  ear  (the  helix),  the  deposits  in  the  eyelids,  around 
the  tendons,  in  the  tibrous  textures  of  the  palms  of  tlie  hands  and 
plantar  tissues,  are  composed  of  inflammatory,  necrotic,  and  hyaline 
elements  containing  a  varying  amount  of  sodium  biurate. 

5.  Glycogen  Infiltration.^ — Glycogen,  like  fat,  is  a  normal  constituent 
of  liver  tissue,  arising  from  the  metabolism  of  grape-sugar  by  the  ex- 
traction of  a  molecule  of  water: 

Grape-sucar.        Water.         Glycogen. 
C,H„0,    -    H,0    =    C.H.oOi 

That  it  can  also  be  produced  from  albumins  there  seems  no  reasonable 
doubt;  but  the  uncertain  composition  of  the  proteid  bodies  makes  the 
chemic  change  of  albumin  into  glycogen  an  unsolved  problem  in  physiolo- 
gic chemist^\^  While  produced  normally  in  the  organism,  it  is  in  diabetes 
that  its  most  remarkable  generation  is  observed.  When  we  have  solved 
the  pathology  of  diabetes,  the  production  of  glycogen,  and  ])articularly 
its  tissue  infiltrations,  may  become  apparent.  It  has  a  rather  remark- 
able resemblance  to  amyloid  material,  and,  still,  that  it  is  not  the  same 
can  be  easily  established.  It  reacts  with  an  aqueous  solution  of  iodin 
very  much  as  amyloid  material,  but  does  not  give  the  blue  with  iodin 
and  sulphuric  acid;  if  treated  with  ptyalin  or  amylopsin,  it  quickly 
loses  its  iodin  reaction;  while  amyloid  is  insoluble  in  water,  glycogen 
is  freely  soluble.  Glycogen  is  converted  postmortem  into  grape-sugar. 
The  extraction  of  glycogen  from  the  liver  is  accomplished  by  dissolving 
it  in  an  alkali  and  precipitating  by  alcohol.  It  is  a  white  powder,  freely 
soluble  in  water,  giving  the  solution  an  opalescent  tint. 

Dcmoiistration. — To  demonstrate  glycogen  in  the  tissues,  use  an- 
hydrous alcohol  for  fixation,  infiltrate  with  celloidm,  and  harden  in 
cedar  oil  and  chloroform  (p.  43).  For  staining,  Barfurth  advises  a 
glycerin  solution  of  iodin.  and  Ehrlich  a  syrupy  solution  of  iodin  in 
gum  acacia.  Bv  either  of  these  solutions  it  stains  brown,  like  amyloid, 
but  is  differentiated  by  the  insolubility  of  the  last-named  Ixjdy.     Fixa- 

•  For  full  bibliography  see  Chantemesse  and   P(Hl\vyssotsky.   "  L*-   iv,  ...v.,,< 
Gtodraux,"    1901,  pp.   242  to  246.     Spczia,   "Lajutt."   May  23.    k^ 
Best,  "Deut.  med.  Wwh.,"   1902.  No.  5.  Vcrcins-Bfil..  p.  36.     Hcli 
intemat.  de  Pharmacodvn.  et  de  Thcrap.."  vol.  xii.  fasc.  ii  and  iv.     iluU-iui. 
"Edinburgh  Medico-Chirurgical  Soc.,"  Feb.  3.  1004.     W'^lff.  "Zoit.  f  klm.  Med., 
Bd.  li.  p.  407.      Driessen.  'Centralbl.  f.  allg.  Path..'  F< 


240  GENERAL  PATHOLOGY. 

tion  in  absolute  alcohol  lessens  its  solubility  but  does  not  render  it 
insoluble.  On  account  of  the  readiness  with  which  glycogen  is  dis- 
solved it  has  been  recommended  to  secure  the  iodin  stain  by  exposing 
thin,  undried  cover-glass  spreads  to  the  vapor  of  iodin  and  mounting 
the  film  in  a  saturated  glycerin  or  gum  acacia  solution  of  iodin. 

As  an  infiltration,  glycogen  is  found  in  the  liver,  epithelial  cells 
of  Henle's  loops,  in  circulating  leukocytes,  and  in  pus-cells.  It  is  present 
in  the  leukocytes  in  diabetes,  and  it  is  claimed  that  the  diagnosis  of 
diabetes  can  sometimes  be  made,  before  sugar  appears  in  the  urine,  by  the 
glycogen  reaction  of  the  white  cells.  The  glycogenic  reaction  of  leuko- 
cytes— iodophilia^ — is  seen  in  a  number  of  infectious  processes,  particu- 
larl}^  suppurative  lesions,  and  is  usually  associated  with  leukocytosis. 
Many  tumors  contain  glycogen.  It  is  said  to  be  more  abundant  in  sar- 
coma than  in  carcinoma,  and  often  forms  a  conspicuous  element  in  tumors 
derived  from  adrenal  cells  (hypernephroma)  and  in  neoplasms  of  the 
testicle  and  bone. 

Morbid  Anatouiy. — Organs  showing  glycogenic  infiltration  resemble 
amyloid  organs  with  the  following  exceptions:  The  specific  gravity 
is  low;  there  is  not  the  bacony  density;  anemia  and  brittleness  are 
less  marked ;  the  organs  never  attain  the  size  sometimes  seen  in  amyloid 
disease;  and  the  difference  given  above  in  the  chemic  stain  reactions. 
In  cells  from  which  the-  glycogen  has  been  dissolved  the  protoplasm 
manifests  a  reticulated  appearance,  due  to  the  cavities  left  by  the  re- 
moval of  the  infiltrating  substance;  this  characteristic  is  particularly 
marked  in  the  hepatic  cell,  but  may  also  be  seen  in  the  renal  epithelium 
and  in  neoplastic  cells. 

Cholesterin  Infiltration. — There  is  much  doubt  as  to  this  being  an 
infiltration;  in  degenerative  processes  cholesterin  is  likely  to  be  found, 
but  gives  no  macroscopic  evidence  of  its  presence.  Under  the  micro- 
scope it  may  be  recognized  as  thin,  rhombic  plates  with  not  very  regu- 
lar edges,  and  quite  commonly  each  plate  has  a  small  square  absent  from 
one  comer,  appearing  as  though  it  had  been  cleanly  cut  out.^  In  addi- 
tion to  the  degenerative  processes  already  mentioned,  cholesterin  is 
found  in  the  contents  of  cysts,  and  sometimes  in  inflammatory  exudates 
and  in  atheromatous  areas. 

Hydropic  Infiltration. — -In  edema  the  tissues  involved  are  bathed  in 
the  fluid  that  distends  the  lymph-spaces,  and  the  cells  of  the  area  may 
take  up  a  varying  amount  of  this  fluid.  By  some  this  is  considered 
an  infiltration,  and  is  spoken  of  as  dropsical  or  hydropic  infiltration. 
It  is  practically  always  associated  with  more  or  less  degenerative  change 
in  the  cells,  and  it  has,  therefore,  seemed  to  the  writer  best  to  consider 
it  with  the  degenerations.     (See  Hydropic  Degeneration,  also  Edema.) 

(B)  DEGENERATION. 

Degeneration^  is  characterized  by  retrograde  changes  in  the  proto- 
plasm and  nuclear  structure  of  cells,  and,  though  to  a  lesser  degree, 
of  acellular  tissues.      These  alterations  may  be  recognized  by  chemic 

'  See  Diseases  of  the  Blood,  Part  III,  Chapter  I. 

'  See  illustration  in  chapter  on  the  Microscopic  Examination  of  Urine. 
^  For    full  bibliography  see  Chantemesse  and  Podwyssotsky,   "Les  Processus 
G^n^raux, "  1901. 


INI-II.TRATION    AM)   DKGEN'KR ATION'.  24I 

or  micTochemic  methods  and  can  often  be  seen  in  untreated  cells.  In- 
filtration may  lead  to  degeneration,  and  degenerations  may  \>c  accom- 
panied by  infiltrations;  the  processes,  however,  may  be  distimt.  Not- 
withstanding the  entity  of  each,  an  infiltration  may  be  associated  with 
a  degeneration,  the  two  tissue  changes  apparently  going  on  side  by  side, 
thus  affording  an  obscure  picture  of  both.  In  such  com]jlex  processes, 
however,  the  degeneration  is  likely  to  be  the  lesion  that  is  most  detri- 
mental, and  while  it  may  have  been  preceded  by  the  infiltration,  or  the 
infiltration  may  have  arisen  after  the  inception  of  the  degeneration, 
still,  the  degenerative  lesion  will  constitute  the  important  i)atholf)gic 
phenomenon.  Degenerations  are  also  known  as  metamorphoses. 
Occasionallv  a  degeneration  is  spoken  of  as  a  necrobiosis;  this  ti-nn  is 
not,  however,  correct,  as  the  latter  condition  implies  molecular  death, 
and  an  organ  or  a  cell  may  be  degenerated  and  may  not  as  yet  be  dead, 
although  ultimately  the  cell  may  perish.  The  degenerations  are  paren- 
chvmatous.  fattv,  hvdropic,  colloid,  mucoid,  hyaline,  and  corneous. 

I,  Parenchymatous  degeneration,  also  known  as  cloudy  swelling, 
granular  degeneration,  and  parenchymatous  metamorphosis,  consists  of 
a  preci|ntate,  within  the  cell  protoplasm,  of  what  seems  to  be  albumin, 
or  other  cell  .proteid,  in  a  finely  granular  form.  The  nucleus  of  the 
cell  is  obscured,  or  even  hidden,  by  minute  granules,  and,  late  in  the 
process,  may  be  destroyed;  the  perinuclear  protoplasm  contains  an 
abundant  granular  precipitate;  the  cell  outlines  are  indistinct,  and  the 
entire  body  may  be  disintegrated.  It  is  probable  that  the  process, 
if  continued,  terminates  in  a  fatty  degeneration,  and  that  the  granular 
bodies  seen  are  eventually  converted  into  oil.  The  cell  may  again 
be  cleared  up  by  the  use  of  dilute  acetic  acid  or  a  strong  alkali.  The 
nucleus  often  becomes  visible,  although  the  granular  bodies  may  merely 
agminate  and  not  disappear. 

Causes. — High  temperature;  poisoning  by  carbonic,  phosphoric,  and 
arsenious  acids,  and  by  the  salts  of  mercury,  copper,  antimony,  etc. ;  in- 
tense or  long-continued  hyperemia,  vascular  stasis,  and  edema;  inflamed 
mucous  membranes  usually  manifest  the  change  to  a  high  degree;  a  simi- 
lar process  is  seen  in  inflammation  of  muscle:  c.  g.,  acute  myocarditis; 
in  acute  yellow  atrophy  of  the  liver  numbers  of  the  cells  are  found 
granular  and  many  of  them  fatty  to  a  high  degree;  any  malnutrition 
mav  simulate  the  condition,  and  many  poorly  nourished  gland-cells, 
particularly  in  atrophic  processes,  show  the  change.  Bacteria  and  their 
products,  as  well  as  other  organic  poisons, — the  latter  due  to  faulty 
metabolism  or  deficient  excretion,  or  to  combinations  of  both  ]  • 
— venoms,  etc.,  are  also  causes.  An  examination  of  the  ca 
given  discloses  the  fact  that  all  are  essentially  toxic.  Halhburt(>n  i.  .;  i> 
that  the  cell  changes  seen  in  high  temi)eratures  resemble  necroses  ni"!-- 
than  degenerations;  their  toxic  origin  can  not  be  questioned. 

Morbid  A  natoniy.~The  affected  organ  is  swollen,  cloudy  or  opaquf  on 
its  surface,  appearing  cooked,  softer  than  normal,  and.  when  the  pr^  ■ 
is  uncomplicated,  there  is  evidence  of  anemia,  but,  as  commonly  - 
the  amount  of  blood  in  the  part  is  increased:  f.,i:..the  cloudy  swc 
seen  in  the  kidney  may  be  the  initial  stage  of  inflaii  .ind  tiie 

organ,  under  such  circumstances,  is  usually  distinctly 

Termination. — If  the  cause  be  withdrawn  early,  it  is  j  j^.-ahle  '  ■^' 
recoverv  of  the   cell   mav   occur;  if  the  cause  continue   to  act.   i.> 


242 


GENERAL  PATHOLOGY. 


degeneration  ensues,  the  cells  are  destroyed,  and  new  cellular  elements 
must  be  produced  by  the  remaining  structures,  including  the  connective 
tissues. 

Demonstration. — The  alterations  previously  described  in  the  gross 
organ  usually  enable  one  readily  to  recognize  the  condition.  Ex- 
amination of  fresh  cells  obtained  by  scraping  the  surface  of  the  tissue 
involved  may  offer  confirmator}^  evidence,  to  be  considered  with  the 
gross  appearance.  Too  much  confidence,  however,  can  not  be  placed 
in  the  examination  of  detached  cells.  In  such  cells  the  granules  clear  up 
or  agminate  when  treated  with  a  one  per  cent,  aqueous  solution  of  acetic 
acid.  They  are  not  soluble  in  alcohol,  ether,  chloroform,  or  other  agents 
that  dissolve  fat,  nor  are  they  blackened  by  osmic  acid.  Pieces  of 
the  organ  under  observation  should  be  fixed  in  an  osmic  acid  solution 
(see  pp.  T,;^  and  34),  infiltrated  with  celloidin  (paraffin  is  not  applicable), 
and  sectioned  in  the  usual  manner.  The  granules  are  not  blackened 
by  this  process.  Tissue  fixed  in  corrosive  sublimate  or  in  Zenker's 
fimd  (see  pp.  34  and  35),  sectioned,  and  stained  with  hematoxylin  and 
eosin  will  commonly  show  the  alterations  to  advantage.  The  intensity 
with  which  the  granules  take  the  acid  anilin  dyes  is  always  notable. 


i^ 


Fig.  138. — Cloudy  Swelling  of 
THE  Epithelial  Lining  of 
THE  Kidney  T  u  b  d  l  e  . — 
{Flutlerer .) 


v^'jiRu 


Fig.  139. — Granular  Degener- 
ation OF  A  Muscle-fiber, 
Last  Stage,  Nearly  Fatty. 
— (Scltmaus.) 


Fig.  140. — Cloudy  Swelling  of 
THE  Liver  Cells.  X  250  diam- 
eters.— (Schmaus.) 


2.  Fatty  Degeneration  or  Fatty  Metamorphosis.^ — This  probably 
represents  but  a  later  stage  of  the  preceding.  In  the  cells,  at  this  stage 
of  the  process,  the  granular  bodies,  before  noted,  are  replaced  by  minute 
oil  drops;  the  nucleus  is  destroyed  and  can  not  be  made  to  reappear; 
the  cell  is  shrunken  and  not  swollen;  its  outlines  are  apt  to  appear 
irregular,  or  evident  cell  dissolution  may  be  manifest.  The  oil  drops 
usually  are  smaller  and  do  not  run  together  as  in  fatty  infiltration, 
although  this  difference  is  not  constant  nor  characteristic.  The  com- 
pound granule  cells  in  brain  softening  represent  a  type  of  fatty  degener- 

^  Christian.  "Jour.  Med.  Research,"  Aug.,  1903,  p  109.  Rosenfeld,  "Berl. 
klin.  Woch.,"  1904,  Nos.  22  and  23.  Orgler,  "Virchow's  Arch.,"  Bd.  176,  No.  3. 
Fischler,  "Virchow's  Arch.,"  clxxiv,  2.  Waldvogel,  "Virchow's  Arch.,"  1904, 
Bd.  clxxvii.  Dietrich,  "Miinch.  med.  Woch.,"  Aug.  23,  1904,  p.  1510.  Christian, 
"Johns  Hopkins  Hosp.  Bull.,"  Jan.,  1905,  p.  i.  Shattock, " Jour.  Path,  and 
Bact.,"  Dec,  1903,  p.  234.  Arnold,  "Miinch.  med.  Woch.,"  Oct.  27,  1903, 
p.  1857.  Ribbert,  "Deut,  med.  Woch.,"  1903,  No.  44.  Dietrich,  "Arbeit,  a.  d. 
Path.  Inst.,"  Tubingen,  1904,  Bd.  5,  H.  i.  Torri,  "II  Policlinico, "  Nov.,  1902. 
Leick  and  Winckler,  "Arch.  f.  exp.  Path.  u.  Pharm.,"  vol.  xlviii,  p.  163. 


INIMI/IRATION'    AND   DHGENIiR  ATK  )N'. 


243 


ated  cells.     The  cellular  debris    in   the  affected  structures   is    usually 
abundant. 

Causes. — (i)  The  causes  already  j^ivcn  for  tloudy  swelling;  (2) 
anemia;  (3)  some  of  the  forms  of  necrosis  arc  a(H(imj)anied  by  fatty 
degeneration:  c.  i^.,  caseation.  Total  or  circumscribed  fatty  defenera- 
tion usuallv  results  from  embolism,  infection,  or  the  noxious  influence 
of  bacterial  toxins  and  allied  agents.  The  relation  of  anesthesia,  par- 
ticularly by  chloroform,  to  fatty  degeneration  is  not  fully  explained. 
The  studies  of  Guthrie^  go  to  show  that  the  prolonged  administration 
of  chloroform  may  give  rise  to  fatty  degeneration  of  the  organs,  par- 
ticularly  the   liver. 

Morbid  AiiatoDiy. — As  soon  as  tlic  removal  of  fat  by  absorption 
begins,  the  organ  diminishes  in  size,  becomes  soft,  almost  pultaceous,  oily 
to  the  touch,  and  greases 
the  knife  with  which  it  is 
cut.  The  afifected  part  is 
paler  than  normal,  yellow 
in  color,  markedly  anemic, 
and  may  be  the  seat  of  in- 
terstitial or  parenchyma- 
tous hemorrhage  due  to 
the  degenerative  processes 
involving  the  capillaries. 
The  color  of  the  organ  may 
not  be  uniform,  but  mot- 
tled, as  a  result  of  the  pro- 
cess being  more  active,  or 
more  marked,  or  at  a  later 
stage  at  some  points.  The 
color  is  also  influenced  by 
the  amoimt  of  blood  in  the 
tissue  and  by  the  presence 
or  absence  of  hemorrhage 
or  of  associated  pigment. 
The  conversion  of  the  pro- 
teid  matter  into  fat  leads 
to  a  reduction  in  the  spe- 
cific gravity.  The  paren- 
chymatous cells  manifest 
the  alteration  earlier  and 
in    a    more    characteristic 

manner  than  the  connective-tissue  elements,  which  may  escape.  W  hen 
the  process  is  focal  and  marked,  and  in  certain  tissues.— as.  for  example, 
the  central  nervous  svstem,— the  softening  may  go  on  to  complete 
liquefaction.  (See  Softening  of  the  Brain.)  Recent  studies  seem  to 
indicate  that  the  condition  ordinarily  called  fatty  degenerations  is.  in 
certain  locations,  a  form  of  what  has  more  recently  been  designated 
autolvsis.  Christian's  studv  of  the  presence  of  fat  in  the  resolving 
croupous  pneumonia  mav  be  considered  as  corroborative  of  flcxncrs 
views  as  to  the  method  (autolysis)  by  which  this  disease  normally  under- 
goes resolution. 

»  "Lancet."  July  4.  1903.  P- .*°- 


lio.  141.     Kii>Nh\,  Karlv  Staok  of  Iatty  DECE.NERAT10S  or 

THK  EpITHKLILM  f)F  THE  CoNNOLCTED  TOBB;    rSOMACASE 
DF  I'F.RNinOfS  .'\nKMIA. 

t  )smic  acid  prcp-iMlion.     T.-irts  of  three  convoUilcd  IuJ>cs  and  one 
rillcclinK   tube  arc   shown.     The   epiiluliiim   M   two  ol    Ihr 


convoluted   tubes,  near  the  center  of  thi-  dr^  wir 
of  advanced  Kfanul.ir  and    less    marke<l 
protopl.Tsin  is  Rr.anular  .ind    fr.iK"ienlin« 
lets  of  fat  that  have  born  blackened  by  the 


i«   Ov 


rhc 

rop- 


244  GENERAL  PATHOLOGY. 

Fatty  degeneration  affects  particularly  epithelial  surfaces  and  glan- 
dular viscera,  muscles,  nerves,  and  blood-vessels;  occasionally  it  is  ob- 
served in  the  brain,  and  there  constitutes  a  variety  of  softening.  In 
certain  localities  the  process  is  apparently  physiologic:  for  example,  the 
production  of  fat  by  degeneration  of  the  central  cells  of  the  acini,  in  the 
mammary  gland,  leading  to  the  formation  of  milk,  and  the  fatty  change 
seen  in  the  uterus  after  labor.  (See  Fatty  Degeneration  of  the  Heart, 
Blood-vessels,    Liver,   etc..  Part  VII.) 

Deiiwiistratiou. — The  highly  refractive  oil  globules  can  usually  be 
recognized  under  the  microscope.  In  fresh  tissues  the  affected  cells 
are  not  cleared  up  by  acetic  acid;  they  are  blackened  by  osmic  acid;  the 
black  or  brownish-black  granules  produced  by  treating  fat  with  osmic 
acid  are  not  soluble  in  alcohol  during  the  subsequent  dehydration,  but 


y»''*ij» 


m 


Fig.  142. — Heart,  Transverse  and  Oblique  Sections  of  Muscle-fibers,  showing  Fatty  Degeneration. 
Osmic  preparation,  from  case  of  pernicious  anemia. 

may  undergo  partial  solution  during  the  process  of  clearing  for  par- 
affin infiltration,  and  particularly  when  subjected  to  the  action  of  fat 
solvents,  such  as  chloroform,  turpentine,  xylol,  etc.  For  the  demon- 
stration in  sections  fixation  in  alcohol  is  not  applicable.  Tissues 
should  be  fixed  in  one  of  the  osmic  acid  solutions  (see  pp.  7,7,  and  34), 
dehydrated,  infiltrated  with  celloidin,  and  sectioned.  The  fat  globules 
will  be  blackened  by  this  method.  Blocks  of  tissue  may  be  fixed  in 
Miiller's  fluid  (see  p.  31)  or  in  Orth's  fluid  (see  p.  31)  or  in  a  ten  per 
cent,  solution  of  formaldehyd  for  a  week  or  ten  days.  The  tissue  is 
then  transferred  to  Marchi's  fluid,  which  consists  of : 

Mtiller's  fluid, 2   parts. 

One  per  cent,  aqueous  solution  of  osmic  acid,.,   i   part. 


INFILTRATION    AND    DKP.KNRR  ATION  .  .'.JS 

The  tissue  is  permitted  to  remain  in  this  solution  for  a  week  or  ten  days. 
For  successful  treatment  the  blocks  of  tissue  should  he  very  small - 
not  over  two  to  iive  millimeters  in  thickness.  Embedding  in  cclloidin 
is  permissible.  After  cuttintj;,  the  sections  are  cleared  in  cedar  oil  and 
mounted  in  balsam  without  staining.  The  fat  globules  will  be  black 
or  brownish-black.  When  desired,  sections  may  be  stained  in  the  usual 
manner,  which  will  permit  an  examination  of  the  nuclei  and  of  the 
associated  structures  to  advantage  (Figs.  142  and  143).  Paraffin  infiltra- 
tion does  not  yield  so  satisfactory  or  trustworthy  results  as  celloidin.  as 
the  preliminary  clearing  agents  are  liable  to  extract  a  ])art  of  the  fat. 

Scharlach  R,  .Sudan  III,  and  F'ettponceau  are  stains  useful  for  the 
demonstration  of  fat  in  cells  or  in  tissue.  Sudan  III  is  commonly  em- 
ployed. A  saturated  solution  of  the  dye  in  seventy  per  cent,  alcohol 
is  the  most  convenient  strength.  The  suspected  fluid  and  cells  are 
spread  upon  a  cover-glass  and  fixed  in  formalin  vapor  for  five  or  ten 
minutes.  The  film  is  then  washed  in  water,  rapidly  rinsed  with  seventy 
per  cent,  alcohol,  and  flooded  with  the  alcoholic  solution  of  the  stain. 
Afer  ten  minutes  the  dye  is  quickly  washed  ofT  with  seventy  per  cent, 
alcohol,  dried  and  mounted  in  glycerin,  glycerin-jelly,  or  Farrant's 
medium.*  Scrapings  from  the  incised  surfaces  of  organs,  or  small 
fragments  torn  to  pieces  by  needles,  may  be  treated  in  the  same  way. 
For  the  demonstration  of  fat  in  fresh  tissues  the  specimen  may  be 
fixed  in  formalin,  Orth's  fluid,  or  Zenker's  solution,  and  sectioned 
with  a  freezing  microtome;  sections  are  stained  twelve  to  twenty- 
four  hours  in  hematoxylin  diluted  with  water,  followed  by 
frequent  changes  of  water  until  the  color  is  no  longer  extracted. 
The  sections  are  then  placed  in  the  alcoholic  solution  of  Sudan 
III  for  fifteen  to  twenty  minutes,  rapidly  washed  in  seventy  per 
cent,  alcohol,  transferred  to  water,  and  mounted  in  glycerin,  glycerin- 
jelly,  or  Farrant's  medium.  For  the  demonstration  of  fat  in  tube  casts 
the  urine  should  be  sedimented  and  the  deposit  washed  in  several  changes 
of  water.  A  drop  of  the  fluid  containing  the  casts  is  mixed  with  an 
equal  volume  of  seventy  per  cent,  alcohol  and  a  drop  of  the  alcoholic 
solution  of  the  stain  added.  In  this  fluid,  examined  under  the  micro- 
scope, the  fat  can  easily  be  identified  within  the  epithelial  cells  or  casts. 
Sudan  III  stains  the  larger  fat  droplets  a  rather  deep  scarlet;  the  smaller 
particles  are  golden  vcllnw.     The  reaction  seems  to  be  finite  selective.' 

3.  Hydropic  degeneration,  or  hydropic  metamorphosis  (cellular 
dropsy,  cellular  vacuolization),  is  ])ractically  an  intracellular  edema. 
The  affected  cells  arc  very  much  larger  than  normal,  and  contain  many 
so-called  vacuoles,  usually  in  the  ])erinuclear  protoplasm,  although  the 
nucleus  may  be  involved.  The  evident  cell  damage  is  less  than  in 
parenchymatous  degeneration,  but  may  l)e  most  marked  when  the  two 
processes  are  associated,  as  is  not  uncommonly  the  case. 

Games. — In  many  instances  the  process  is  clearly  toxic.  Exactly 
how  poisons  induce  this  form  of  change  can  not  be  stated.  It  is  seen 
particularly  in  edema,  inflammation,  infectious  processes,  and  degenera- 

'  Farrant's  medium  cim.sists  of  plycorin.  pum  arabic.  arscnious  acid,  and  water. 
It  is  difficult  to  prepare  and  had  best  be  puriha.«;ed  from  a  dealer  in  .suj<|'l«cs.  In 
some  climates  it  forms  a  satisfactop.-  medium  for  per •:•■• 

'  For  further  review   of   methods   sec    Fischler.      '  Tath.. 

Xov.  30.  1904.  p.  9n-     Stransky.  "  Ncurolog.  Centra:   .  .  p.  ^^S. 

Mever,  "Centralbl.  f ."  Nervenheil.  u.  Psych.."  1903,  vol.  xiv,  No. 


246  GENERAL  PATHOLOGY. 

tive  lesions  in  general  when  affecting   the    large  ganglion  cells  of  the 
central  nervous  system. 

Hydropic  degeneration  is  frequently  observed  in  the  cells  of 
epithelial  surfaces,  particularly  the  mucous  membranes,  glandular 
viscera  in  inflammation  and  edema,  edema  of  the  muscular  tissues  in 
which  many  fibers  are  swollen  and,  on  transverse  section,  show  extensive 
central  vacuolation.  The  morbid  anatomy  is  practically  that  of  edema, 
but  hydropic  degeneration  is  often  present  when  no  gross  alteration  is 
manifest. 

Demonstration. — No  specific  method  has  as  yet  been  devised  for  the 
demonstration  of  this  process.  Rapid  and  powerful  fixatives  are  de- 
manded in  order  to  prevent  the  cell  from  emptying  itself  of  the  fluids 
"  before  fixation  is  completed.  Probably  the  best  results  are  obtained 
by  fixing  small  pieces  of  the  tissue  in  corrosive  sublimate  (see  p.  34), 
followed  by  hematoxylin  and  eosin  staining. 

4.  Colloid  degeneration,  or  colloid  metamorphosis,  is  a  process  by 
which  cellular  protoplasm  is  converted  into  a  homogeneous,  gelatinous, 
structureless  substance  called  colloid.  The  exact  cause  of  this  change 
is  not  known;  it  occurs  in  connection  with  epithelial  cells,  to  which  it  is 
practically  restricted.  It  is,  therefore,  a  common  phenomenon  in  glandu- 
lar structures  where  exit  is  prevented  by  occlusion  of  the  duct;  it  is  seen 
in  the  kidney  and  in  ovarian  cysts,  it  occurs  in  goiter  and  in  cancerous 
masses.  The  constancy  with  which  it  is  found  in  the  thyroid  gland  has 
led  many  observers  to  beHeve  that  it  is  a  normal  constituent  of  that  organ, 
and,  when  greatly  increased  in  amount,  the  condition  is  spoken  of  as 
colloid  goiter.  The  exact  chemic  nature  of  the  material  has  not  been 
definitely  settled;  it  is  not  precipitated  by  alcohol  or  acetic  acid,  it  is 
not  readily  soluble  in  water,  and  is  not  rendered  opaque  by  chromic  acid. 

Macroscopically,  the  material  is  gelatinous,  stringy  or  ropy,  and  is 
usually  colorless,  but  may  be  slightly  bluish  or  yellow. 

Microscopically,  it  will  occasionally  be  observed  to  be  arranged  in 
concentric  masses.  It  does  not  stain  well  with  the  anilin  dyes,  but 
stains  with  carmin. 

Colloid  degeneration  of  muscle  has  been  described  by  Zenker,  and  is 
closely  allied  to  the  hyaline  degeneration,  which  he  also  describes.  Col- 
loid material  is  found  in  some  cancers,  particularly  in  those  of  the  ali- 
mentary canal;  it  is  also  found  in  cysts  possessing  an  epithelial  wall. 
Colloid  transformation  occurs  in  the  cerebral  vessels,  where,  according  to 
Mallory,  it  is  particularly  subject  to  subsequent  calcareous  change.  (For 
demonstration  and  differentiation  from  amyloid,  mucoid,  and  hyaline 
material  see  paragraph  following  Hyaline  Degeneration.) 

5.  Myxomatous  degeneration,  also  known  as  mucoid  degeneration  or 
myxomatous  metamorphosis.^  Myxomatous  material  is  normally  found 
in  Wharton's  jelly  and  in  the  vitreous  humor.  The  process  terminates 
in  the  formation  of  a  semifluid,  hyaline  body  containing  a  varying 
quantity  of  mucin.  A  further  study  of  mucin  has  led  to  the  recognition 
of  the  fact  that  what  was  originally  considered  to  be  a  chemic  entity  is 
now  found  to  occur  under  a  number  of  conditions  and  in  more  than  one 
form.  In  epithelial  structures  the  mucin  exists  in  the  mucus  elaborated 
within  certain  of  the  cells,  which  assume,  as  a  result  of  the  accumulation 
in  their  interior,  a  goblet  form,  and  hence  are  called  goblet  cells.  The  free 
end  of  the  cell  opens  and  the  accumulated  contents  flow  out,  the  cell 

'  Chantemesse  and  Podwyssotsky,   "  Les  Processus  Generaux,"   1901. 


INl-lLTkATU)\    AN!)   DEGEN  KR  ATIO  V.  247 

returns  to  its  normal  shape  and  resumes  the  manulacture  ot  mucus. 
In  other  instances  the  cell  is  actually  shed,  undergoes  dissolution,  and 
liberates  the  elaborated  product.  During  inflammatory  processes  in  epi- 
thelial surfaces  the  ciuantity  of  mucus  produced  is  notably  increased.  The 
production  of  mucoid  material  is  not,  however,  restricted  to  the  epithelial 
tissue,  but  is  intimately  associated  with  the  connective  tissues,  and  arises 
from  the  transformation  of  the  cell,  or,  more  frequently,  and  probably 
more  truly,  of  the  intercellular  substance  into  a  jelly-like  material  con- 
taining mucin.  Chemically,  the  material  seems  to  be  made  up  of  com- 
plex albuminous  compounds  in  which  mucin  is  abundantly  present. 
The  affected  area  is  gelatinous  and  trembling,  almost  perfectly  clear, 
and   colorless. 

In  myxedema  the  subcutaneous  and,  to  a  certain  extent,  other  tissues 
are  the  seat  of  marked  swelling,  and  between  the  fibrils  is  intercalated 
a  somewhat  hyaline,  almost  homogeneous  substance,  thatOrd  has  shown 
contains  a  mucin.  Apparently  the  alteration  is  not  identical  with 
some  other  forms  of  myxomatous  degeneration,  but  the  resulting 
product  possesses  a  number  of  the  characters  seen  in  tissues  affected  by 
mucoid  metamorphosis.  Myxedematous  tissues  are  solid,  do  not  pit 
on  pressure,  and  when  incised  yield  practically  no  serum.  The  vas- 
cularity is  greatly  reduced  and  the  nutrition  proportionately  altered. 
(See  Diseases  of  the  Thyroid  Gland.) 

Microscopically,  mucoid  material  is  quite  homogeneous,  and  not 
uncommonly  contains  large  multipolar  cells  with  long,  branching  fila- 
ments. These  form  a  reticulum,  which  supports  the  gelatinous  material 
and  maintains  conformation  of  the  affected  structure;  it  is  not  arranged 
in  concentric  masses,  like  colloid  material.  Mucoid  material  is  precipi- 
tated by  alcohol  and  acetic  acid,  and  is  best  fixed  by  corrosive  sub- 
limate. It  will  absorb  considerable  water,  which  causes  it  to  swell; 
it  does  not,  however,  undergo  solution.  It  is  dissolved  by  neutral  salt 
solutions  and  by  alkalies,  even  in  comparatively  weak  solutions.  (For 
further  remarks  on  demonstration  see  paragraph  following  Hyaline 
Degeneration.) 

As  before  indicated,  mucoid  degeneration  occurs  in  both  connective 
and  epithelial  tissues;  it  is  present  in  certain  connective-tissue  tumors, 
most  commonly  in  myxoma  and  lipoma,  occasionally  in  sarcoma  or 
chondroma,  and  rarely  in  carcinoma. 

6.  Hyaline  degeneration,  also  known  as  vitreous  or  glassy  degenera- 
tion or  hyaline  metamorphosis.     The  exact  nature  of  the  material  i)n)- 
duced.  and  the  method  by  which  it  is  elaborated,  have  not  been  worked 
out ;  the  body  seems  closely  related  to  colloid  material,  but  is  firmer,  more 
fragile,  and  arises  in  a  different  class  of  tissues;  it  is   most  commonl-. 
found  in  the  lymphatic  glands  and  blood-vessels,  including  the  capillaries, 
around  which  it  may  form  a  distinct  mantle;  it  is  occasionally  obser\'ed 
just  outside  the  intima  of  the  blood-vessels  and  around  the  capillar;.- 
"thus  closely  resembling  amyloid  material.     It  does  not.  however    'mv- 
the   amyloid   reaction.      Hyaline   material   is  occasionally 
the  Drain,  in  the  stroma  of  epithelial  tumors,  and  in  the  <'■■ 
ments  of  papilloma  of  the  bladder  and  other  mucous  surtaces.      i 
degenerative  change  obser\'ed  in  the  muscles  in  typhoid  fever,   j  ir 
ticulariv  in  the  abdominal  recti  and  the  muscles  of  the  upper  portion 
of  the  thigh,  has  been  variously  placed.     By  some  it  is  regarded  as  a 


248  GENERAL  PATHOLOGY. 

Special  degenerative  change  restricted  to  muscle ;  by  others  it  is  grouped 
with  the  hyaline  degenerations;  while  still  others  regard  the  change 
as  a  form  of  coagulation  necrosis. 

Amyloid,  colloid,  mucoid,  and  hyaline  materials  are  closely  allied 
bodies.  Thoma,  von  Recklinghausen,  and  Graham  regard  each  as 
representing  but  different  stages  in  the  evolution  of  the  same  body. 
Lardacein  apparently  presents  sufficiently  distinct  reactions  to  entitle 
it  to  be  considered  alone.  That  the  remaining  conditions  are  separable 
by  methods  at  present  at  our  disposal  seems  doubtful.  Differentiation 
by  stain  reaction — the  only  method  at  present  available — is  not  fully 
characteristic  or  always  satisfactory.  Hyaline  and  colloid  materials 
seem  to  select  acid  stains,  while  mucoid  is  commonly  best  stained  by 
basic  dyes.  Pianese  differentiates  these  materials  by  fixing  small 
pieces  of  tissue  (2  mm.  thick)  in  a  mixture  composed  of  15  c.c.  of 
a  I  per  cent,  aqueous  solution  of  chlorid  of  platinum  and  sodium;  5 
c.c.  of  a  0.25  per  cent,  aqueous  solution  of  chromic  acid;  5  c.c.  of  a 
2  per  cent,  aqueous  solution  of  osmic  acid;  and  one  drop  of  chemically 
pure  formic  acid.  After  thirty-six  hours'  fixation  the  tissues  are  washed 
in  flowing  water  and  transferred  to  eighty  per  cent,  alcohol.  Sections 
are  stained  for  half  an  hour  in  the  following  solution : 

Martius  yellow, 0.0 1  gm. 

Acid  fuchsin, o.i    gm. 

Malachite  green, 0.5    gm. 

Distilled  water, 150        c.c. 

Alcohol   (96  per  cent.), 50       c.c. 

After  staining,  wash  in  absolute  alcohol,  treat  with  xylol,  and 
mount  in  xylol  balsam.  By  this  method  mucin  is  stained  sky-blue; 
hyaline,  brick-red;  colloid,  bright  green. 

Corneous  degeneration,  keratoid  metamorphosis,  keratohyaline  de- 
generation, keratosis,  or  hyperkapatosis,  are  a  few  of  the  many  names 
given  to  a  condition  characterized  by  excessive  cornification  of  epithe- 
lium. It  is  an  exaggeration  of  the  normal  process  by  which  the  epi- 
thelium of  the  Malpighian  layer  of  the  skin  is  transformed  into  the 
corneous  stratum.  The  chemic  product  resulting  from  this  change 
is  called  keratin.  This  substance  is  insoluble  in  cold  or  boiling  water, 
in  dilute  acids,  and  in  alkaline  carbonates;  it  resists  digestion  and  putre- 
faction and  is  converted  into  alkaline  albuminates  and  hemialbumose 
by  a  concenerated  caustic  alkali.  When  stained  by  the  method  of 
Gram,  it  is  found  to  contain  numerous  small  granules  (keratinic  granu- 
lations of  Ernst)  which  take  the  dye  intensely.  The  formation  of 
keratohyaline  is  practically  always  most  advanced  in  epithelial  cells 
farthest  from  the  source   of  nutrition. 

Pathologic  keratinization  is  seen  particularly  in  ichthyosis,  kera- 
tosis, and  in  lingual,  buccal,  and  vaginal  psoriasis.  A  large  part  of 
the  typical  cell  nests  of  squamous  epithelioma,  when  fully  developed, 
are  composed  of  keratinized  epithelial  cells.  The  epithelium  covering 
papillomas  and  the  hardened  superficial  layers  of  ordinary  corns  are 
composed  of  keratinized  epithelium.  Cutaneous  horns  usually  consist 
of  more  or  less  perfectly  laminated  epithelial  cells  that  have  under- 
gone this  change.^ 

^  For  fuller  description  of  the  process  see  Chantemesse  and  Podwyssotsky,  "  Les 
Processus  Generaux, "    1901,  p.   154,  bibliography,  p.   207. 


CTTAPTKR   IX. 
NECROSIS. 

Necrosis  is  the  local  death  of  a  part,  as  distinguished  from  somatic 
death.  When  necrosis  of  any  structure  results  from  trauma  apj>lied 
directly  to  the  tissue,  it  is  known  as  direct  necrosis  ;  when  the  change  is 
dependent  upon  causes  applied  througli  the  circulation,  innervation, 
or  degenerative  processes,  it  is  called  indirect  necrosis. 

Causes. — Anything  that  destroys  the  vitality,  c.  t;.,  burns,  scalds, 
and  chemic  destruction  or  injury  sufficient  to  interfere  with  nutrition. 
The  influence  of  trauma  need  but  be  mentioned,  as  the  extensive  lacera- 
tion of  the  cells,  with  the  associated  disturbances  of  circulation,  both 
hemic  and  lymphatic,  makes  cellular  death  inevitable.  The  method 
by  which  poisons  produce  necroses  is  not  always  apparent.  Of  the 
many  toxic  substances  endowed  with  the  property  now  under 
consideration,  certain  of  them  are  inorganic,  such  as  mercur\',  phos- 
porus,  copper,  arsenic,  etc.;  others  are  organized  bodies,  which  may 
be  again  subdivided  into  at  least  three  groups:  (i)  Vegetable  poisons 
(from  the  higher  forms  of  vegetable  life  many  bodies  might  be  men- 
tioned, e.  g.,  oil  of  mustard,  abrin,  ricin,  etc.),  bacteria,  and  bacterial 
poisons,  such  as  the  toxin  of  the  Bacillus  diphtheria;  (2)  poisons  belong- 
ing to  the  animal  kingdom,  such  as  those  elaborated  by  poisonous  rep- 
tiles; (3)  certain  toxic  bodies  produced  by  the  tissues  themselves.  As  an 
example  of  the  noxious  influence  of  the  last  group,  it  is  Vmt  necessary 
to  refer  to  the  extensive  hepatic  necroses  that  occur  in  uremia,  and  in 
that  partictilar  form  of  intoxication  known  as  eclampsia.'  The  associa- 
tion of  inflammation  with  necrosis  may  be  either  primary  or  secondan,' : 
that  is  to  say,  necrotic  processes  may  give  rise  to.  or  be  followed 
by,  inflammation;  on  the  other  hand,  inflammation  is  always  associated 
with  a  varving  degree  of  necrosis.  Obstruction  to  the  circulation — 
arrest  of  the  arterial  influx,  capillary  flow,  or  of  the  venous  exit — may 
cause  necrosis;  lymphatic  obstruction  may  have  practically  the  same 
effect;  capillary  stasis,  thrombosis,  or  rhexis  is  usually  followed  by 
necrosis  of  the  tissues  involved. 

As  nutrition  is,  in  part,  governed  by  the  trophic  nerves,  it  is  held 
that  certain  necrotic  changes  result  from  lesions  of  these  nerves  or  the 
central  nervous  system  acting  through  them.  Such  necrotic  processes 
are  known  as  neuropathic  necroses. 

The  cause  of  any  ^ivon  necrotic  process  may  have  been  complex. 
more  than  one  element,  and    in  some  i-  many  factors,  entering 

into  its  formation.     In  the  weak  and  .i  i.  after  fevers,  in  malig- 

nant   diseases,    and,    in    certain    instan<.eo.    luUowing    1  •  shock. 

necrotic  changes  are  induced  by  injuries  and  other  cau  in  the 

physicallv  strong,  would  give  rise  to  but  little  or  even  nu  nuportant 

'  See  page  80. 
240 


250  GENERAL  PATHOLOGY. 

tissue  alteration.     As  examples  of  necrosis  arising  in  part  through  such 
influences,  marasmic  and  senile  necroses  may  be  mentioned. 

Results.— The  tissue  involved  inay  undergo  (i)  regeneration  or  the 
nearest  approach  thereto,  repair;  (2)  absorption,  more  or  less  complete; 
(3)  retention  in  some  form  or  another;  or  (4)  it  may  be  discharged.  The 
possibility  of  associated  or  subsequent  inflammation  is  not  to  be  for- 
gotten. 

1.  Regeneration  and  Repair. — In  some  instances  the  necrosed  elements 
are  thrown  off  or  absorbed,  and  adjacent  cells  or  embryonic  constituents 
of  the  tissues  involved  may  produce  new  tissue  structurally  and  physio- 
logically identical  with  that  lost,  in  which  case  the  lost  structures  are 
said  to  be  regenerated.  More  frequently,  absorption  of  the  liquefied  ele- 
ments occurs,  and  repair  proceeds  to  the  formation  of  cicatricial  tissue, 
which  remains  as  a  scar  occupying  the  area  of  the  original  lesion. 

2.  Absorption  is  possible  only  when  the  liquefaction  can  be  complete 
and  when  bacteria  do  not  gain  access;  such  absorption  is  typified  in 
bruises  in  which  the  extruded  blood-cells  are,  in  time,  completely  re- 
moved. 

J.  Retention. — The  entire  mass  may  be  retained,  or  partial  absorption 
and  reparative  changes  may  leave  but  a  part;  thus,  if  an  infarct  cut 
off  the  blood-supply  in  a  branch  of  the  renal  artery,  the  area  involved 
— say,  a  part  of  a  pyramid — dies;  after  certain  degenerative  processes, 
leukocytes  and  fixed  connective-tissue  cells  wander  in  and  convert  the 
mass  into  embryonic  tissue,  from  which  granulation  tissue  is  evolved 
and  eventually  cicatricial  tissue  (organization).  Only  a  part  of  the 
involved  tissue  may  be  retained,  and  this  may  be  much  altered:  e.  g., 
in  the  blood  cyst,  or  hematoma,  a  fibrous  capsule  may  be  formed  sur- 
rounding the  escaped  blood.  Some  of  the  fluid  contents  mav  be  re- 
moved by  the  absorbents,  and  the  remaining  solid  material,  derived 
from  the  clot  and  cellular  elements,  becomes  permanent,  or  degenera- 
tive changes  may  convert  the  mass  into  a  cyst. 

4.  Discharge. — The  necrotic  mass  may  be  thrown  off,  as  in  gan- 
grene, or  it  may  be  slowly  disintegrated,  as  in  suppuration,  ulceration, 
and  caries. 

Forms  of  Necrosis.— Liquef action  necrosis,  coagulation  necrosis,  fat 
necrosis,  cheesy  necrosis,  sphacelation  en  masse  or  gangrene. 

I.  Liquefaction  or  colliquative  necrosis  arises  as  the  result  of  in- 
fection, particularly  by  pyogenic  organisms,  and  is  induced  by  irritants 
that  are  not  sufficiently  active  to  produce  coagulation  necrosis.  It 
differs  from  coagulation  necrosis  in  the  absence  of  coagulation;  there 
is  the  same  infiltration  of  the  tissues  with  fluid,  but  coagulation  does 
not  occur.  Pus  production  resulting  from  infection  represents  a 
type  of  liquefaction  necrosis,  in  that  bacterial  products,  and  pos- 
sibly other  bodies,  liquefy  the  intercellular  substance  retaining 
the  leukocytes  and  other  cellular  elements,  and  thus  convert 
the  area  involved  into  a  liquid.  Liquefaction  necrosis  is  sometimes 
seen  to  follow  coagulation  necrosis,  and  coagulation  of  previouslv  lique- 
fied areas  is  occasionally  observed.  It  has  been  shown  that'  tissues 
normally  contain,  or  may  produce,  substances  possessing  the  power  of 
hquefying  structural  elements.  As  a  result  of  such  liquefaction  (auto- 
lysis) absorption  is  rendered  possible. 

Morbid  Anatomy. — The  gross  appearance  depends  largelv  upon  the 


NECROSIS. 


»SI 


.1 


tissue  involved,  aiul,  to  a  certain  extent,  upon  the  cause.     The  increased 
amount  of  fluid  in  the  part  may  make  it  softer  than  normal— indeed,  it 
may  fluctuate;  in  other  situations  the  associated  increased  tension  ^ives 
rise  to  apparent  induration,  which  disappears  on  incision  or  puncture 
permitting  the  escape  of  some  of  the  fluid.     In  the  absence  of  coloring- 
matters,  including  blood  pigment  or  its  derivatives,  the  color  is  lighter 
than  the  normal.     Concurrent  fatty  degeneration  leads  to  the  presence 
of  minute  oil  drops, — an  emulsion, — -which  may  give  the  softened  area 
a    greasy    appearance.      Histologically,    the    structural    elements    pass 
through  hydropic,  fatty,  and  other  degenerative  processes,  and,  finally, 
may  no  longer  contain  a  single  structurally  normal  constituent.     Ab- 
sorption, retention  in  part 
or    as    a    whole,   and    dis- 
charge are  possible  termin- 
ations; repair,  more  or  less  r- 
complete,  occasionally  oc- 
curs,   but    regeneration   is 
extremely     rare,    if    even 
possible. 

The  results  of  liquefac- 
tion necrosis  are  seen  in 
the  fluid  exudate  in  burns, 
vesicles,  etc.,  and  in  soften- 
ing of  the  central  nerv'ous 
system ;  secondary  lique- 
faction of  coagulated  exu- 
dates occurs  in  croupous 
pneumonia,  blood-clots 
and  thrombi. 

2.  Coagulation  necrosis 
occurs  as  a  part  or  se- 
quence of  infection;  as  a 
result  of  embolism  or  capil- 
lary plugging.  In  areas  of 
interstitial  hemorrhage  and 
in  blood-clots,  the  mass 
undergoes  coagulation  ne- 
crosis. Usually  the  affected 
tissues  are  matted  together 
with  fibrin,  which  entangles 
whatever  cellular  elements 

be   present;    occasionally    fibrin   is 


f^. 


Fig.  143.— I.NTERf ostai    Mi  ^'  1  k,  Transvebse   Sectio.v.  frum  a 
Case  of  Epipneumomc  Pleurisy,  showing  Area  o»  Cjjaoc- 

LATioN  Necrosis. 
Tissue  futed  in  2^nki  r 
Necrotic  area  in 
musclc-tibcrs  ni  i 
clear  leukocyte.-, 
margin  of  the  n 
fibers  (hydri'irii 


the  field. 


mav 


absent  or  not  demonstrable, 
as  on  or  in  the  mucosa  in 


When  occurring  in  superficial  structures 

diphtheria,  the  fibrin  found  may  be  hyaline  or  homogeneous,  fibrillar. 

or.  in    some   instances,   granular.      The   view  at  one   time    If  '  "     " 

fibrin  of   the   blood   was  essential    to   the   process,   is   now   .. 

to    be    incorrect,    as    lymph    containing    fibrinogen    may    inducc    ihc 

change.     Zenker's  degeneration  of  muscle  is.  by  some,  held   to   » .-  .i 

form  of  coagulation  necrosis.     As  an  example  of  coagulation 

following  infection   may  be  mentioned   its  occurrence   in   di; 

tuberculosis,  typhoid  fever,  and  allied  conditions.     It  does  not  scorn 

that   bacteria   at   the  point  of   necrosis  are   necessar>',   bv»    ''^-^    ''^<- 


252  GENERAL  PATHOLOGY. 

process  may  be  engendered  by  the  activity  of  bacterial  products ;  that  it 
may  be  due  to  chemic  agents  circulating  in  the  blood  is  shown  by  the 
intravascular  injection  of  abrin  or  ricin,  which  is  followed  by  coagula- 
tion necrosis  in  different  organs.  After  the  tissues  are  matted  together 
by  fibrin,  fragmentation  of  the  nuclei  (karyolysis)  and  more  or  less 
complete  dissolution  of  the  cells  occur.  In  active  inflammatory  proc- 
esses, or  in  the  tissues  immediately  adjacent,  coagulation  necrosis  is 
nearly  always  present.  It  not  uncommonly  precedes  caseation,  and 
may  be  present  in  the  neighborhood  of  caseous  areas. 

Morbid  Anatomy. — Early  in  the  process  the  tissues  become  very 
much  firmer  than  normal;  not  uncommonly  the  area  can  be  recognized 
by  palpation,  even  when  situated  some  distance  beneath  the  surface. 
Upon  incision  the  freshly  cut  surface  may  resemble  the  opaque,  glassy 
appearance  of  cloudy  swelling.  Later,  softening  not  uncommonly 
occurs,  which  may  progress  to  liquefaction.  In  the  absence  of  blood 
or  of  blood  coloring-matter  or  its  derivatives,  the  area  is  lighter  than 
normal.  Histologically,  the  cell  outlines  soon  disappear  and  the  normal 
microchemic  reactions  are  altered.  The  nuclei  at  first  stain  very  faintly 
with  the  basic  d3'es,  but  later  not  at  all,  and  just  before  complete  dis- 
solution of  the  cell  its  entire  structure  may  take  the  acid  dye  only. 
Occasionally,  however,  even  late  in  the  process,  fragments  of  nuclear 
chromatin  ma}^  be  irregularly  disseminated  through  the  area,  and  may 
show  as  irregular  granules  taking  the  basic  dye  in  the  midst  of  a  fine 
granular  mass  that  selects  the  acid  stain.  By  suitable  methods  the 
presence  of  fibrin  can  be  shown  at  some  stage  in  the  development  of 
the  process. 

For  the  purpose  of  demonstrating  the  presence  of  this  body  Wei- 
gert's  fibrin  stain  is  recommended.  Sections  of  alcohol-hardened  tis- 
sue are  fastened  to  the  slide  by  an  approved  method.  The  subsequent 
staining  is  conducted  as  follows: 

Anilin  gentian-violet  solution^  two  to  ten  minutes;  rinse  in  normal 
salt  solution;^  apply  solution  of  Lugol  (iodin,  4 parts;  iodidof  potassium, 
6  parts;  water,  100  parts);  rinse  in  water;  blot  with  filter-paper;  dif- 
ferentiate in  a  mixture  composed  of  anilin  2  parts,  xylol  i  part;  com- 
plete differentiation  in  xylol,  which  should  be  applied  and  removed  at 
least  three  times;  when  the  section  becomes  fully  cleared,  mount  in 
balsam.     Dehydration  and  differentiation  ivith  alcohol  are  not  permissible . 

Termination. — Discharge  may  occur  as  in  pseudomembranous  for- 
mation. (See  Pseudomembranous  Infiammation  of  Mucous  Mem- 
branes.) Liquefaction,  absorption,  retention,  or  suppuration  usually 
occurs.  More  or  less  absorption,  followed  by  repair,  is  not  infrequent. 
As  in  liquefaction  necrosis,  regeneration  of  the  destroyed  tissue  is  not 
common.  On  the  surface  of  the  mucous  membranes,  however,  the 
destroyed  cellular  elements  are  not  infrequently  regenerated. 

Coagulation  necrosis  is  possible  wherever  embolism  may  occur,  and 
in  all  forms  of  capillary  stasis;  it  involves  the  cells  of  epithelial 
surfaces  and  glands  made  up  largely  of  epithelium,  such  as  the 
liver;  the  same  condition  has  been  observed  in  the  connective  tissues, 
muscles,  and  fat.      Halliburton^   states    that  the  cell    change  seen  in 

^  For  formula,  see  chapter  on  Bacteriologic  Technic. 
^  Sodium  chlorid,  0.75  per  cent,  in  water. 
^  "Lancet,"  June  22,  1901. 


NECROSIS. 


253 


the  brain  substance  and  thought  to  depend  upon  liigh  temperature 
has  been  recognized  by  Marinesco  as  a  form  of  coagulation  necrosis. 
Angkule'  holds  that  in  all  cases  cerebral  softening  is  a  necrosis,  pure 
and  simple;  it  may  ])rimarily  l)e  coagulativc.  but  rajndly  i)roceeds  to 
liquefaction. 

3.  Fat  Necrosis.- — Whether  this  deserves  a  distinct  position  among 
the  necroses  is  not  fully  determined.  It  is  most  constantly  associated 
with  hemorrhagic  pancreatitis,  in  which  condition  it  occurs  in  the  pan- 
creas, peripancreatic  fat,  and  in  the  fat  of  the  abdominal  wall.  It  has 
been  found  in  other  conditions,  and  with  no  discoverable  lesion  of  the 


Fic.  J44.-1\T  Nfi  R"-~i>  A(  ( ■■\irvvvis'.  Ai  i  i  v    i  1  -  \'  ''  ^- 

The  area  shown  in  the  illustration  is  from  just  Itcneaih  ihf  invcsiitiK  IiIt 
area  of  hemorrhage,     fi.  Fragmented  nuclei  in  area  of  neimsis.     ( 

tion.  Many  other  unaffectc<l  or  but  slightly  changed  fat  cells  are  present  />  I  .it  ..11 111  win.  !i  th. 
is  incomplete.  E,  E.  .Vreas  in  which  the  necrosis  is  practically  complete.  F.  Part  ol  pcnpancreauc 
tissue. 

pancreas.  The  areas  of  fat  necrosis  vary  in  size  from  one  or  two  milli- 
meters to  five  centimeters,  are  usually  spheroid  or  ovoid  in  outline,  are 
white,  yellowish-white,  or  gray,  and  resemble,  in  .1  w.iv    .li^^cniiv.;!'<'l 

'  'Soc.  de  Biol."  March  4.  1905. 

'Williams.   "The  Morbid  Anatomy  and  Etiology*  of 
1900.     Truhart.    "  PankrcaspathoK-pic. "    Toil    I;       •'Mt:: 
gewcbsnckrose,"  Wiesbaden,  1902.      Ponfick.  "Bcitr.  zur  I 
Xckrose,"  1902.     Guthrie.  "Jour.  Amcr.  Med.  Assoc.."  J- 
"Jour.   Med.    Research,"    1003.   vol.  ix,    No.    i.     Hart. 
Jan.  12,  1904.     HatTncr.  "Mtinch.  med.  Woch.."  Aug.  lO,  1904.  ; 
lett.  "Jour.  Med.   Research."  May.   1904.  p.  377- 


254  GENERAL  PATHOLOGY. 

neoplasms  or  tubercles.  Histologically  the  oil  content  of  the  fat  cells 
is  converted  into  a  finely  granular  debris  which  no  longer  takes  osmic 
acid;  nuclear  structures  in  the  affected  area  are  fragmented.  In  the 
earlier  stages  leukocytes  are  absent,  and,  when  infection  does  not 
occur,  play  no  important  part  in  the  process.  In  time  the  necrotic 
tissue  may  be  infiltrated  by  lime  salts;  this  infiltration  is  further  ex- 
plained if  we  accept  the  statement  of  Langerhans  that  the  necrotic 
areas  consist  of  a  combination  of  the  fatty  acids  with  lime  salts.  Some- 
times areas  are  softened,  but  later,  as  a  result  of  the  calcific  matter 
present,  they  become  gritty.  The  presence  of  steapsin,  the  fat  ferment 
of  the  pancreas,  has  led  to  the  belief  that  this  body  is  the  essential 
factor.  Some  hold  that  the  process  depends  upon  bacteria  or  bacterial 
products,  while  others  believe  that  it  is  brought  about  by  trophic  in- 
fluences. Recent  clinical  and  experimental  evidence  indicates  that 
the  change  in  the  fat  is  due  to  the  activity  of  the  pancreatic  ferments, 
and  that  the  older  theories  can  be  discarded. 

4.  Cheesy  necrosis,  or  caseation,  frequently  begins  as  a  coagulation 
or  liquefaction  necrosis,  followed  by  a  fatty  degeneration  of  the  cel- 
lular elements,  and  the  conversion  of  the  mass  into  a  liquid  or  semifluid 
material  resembling  cheese.  In  some  cases  the  fluid  is  taken  up  bv  the 
lymphatics,  giving  rise  to  dry  caseation,  such  as  is  seen  in  old  tuber- 
culous abscesses  in  which  the  substances  resulting  from  liquefaction 
necrosis  have  been  absorbed,  leaving  nothing  but  the  cellular  detritus. 
Caseation  is  not  always  dependent  upon  the  removal  of  the  fluids  and 
the  retention  of  the  solid  particles,  as  is  shown  by  the  fact  that  many 
caseous  areas  undergo  no  diminution  in  size  at  any  period  in  their 
evolution.  This  is  partly  explained  by  the  occurrence  of  cell  migra- 
tion into  the  necrotic  area,  the  newly  arriving  cells  themselves  under- 
going necrosis  and  their  solid  constituents  remaining.  The  entrance  of 
cells  and  fluids,  as  well  as  the  absorption  of  the  latter,  account  for  the 
nodules  retaining  approximately  their  original  size.  In  addition  to  the 
detritus,  arising  from  disintegration  of  the  normal  elements  present,  and 
the  necrotic  cells,  caseous  nodules  may  contain  bacteria.  The  organism 
most  frequently  present  is  the  tubercle  bacillus,  which  may  be  at  times 
demonstrated  in  caseous  nodules  that  are  evidently  old.  Recently 
formed  caseous  areas  are  not  uncommonly  surrounded  by  a  zone  of 
inflammation.  Older  nodules  may,  from  causes  not  well  understood, 
show  recrudescence  of  the  original  process.  SchmolP  has  shown  that 
caseous  products  of  tuberculosis  consist  chiefly  of  coagulated  proteid 
the  elementary  composition  of  which  resembles  albumin,  like  which  it 
maybe  converted  into  albumoses  and  peptone. 

Once  the  caseous  mass  is  thoroughly  encapsulated,  it  becomes 
permanent;  the  capsule  frequently  calcifies,  and  lime  salts  may 
be  infiltrated  into  the  cheesy  material,  converting  it  into  a  stone- 
like structure.  The  condition  can  not  be  properly  said  to  be  a  cure, 
but  only  a  quiescent  stage,  likely  at  any  time  to  be  followed  by  recru- 
descence of  the  original  exciting  cause. 

Causes. — The  process  arises  almost  exclusively  in  connection  with 

tuberculosis,  but  is  occasionally  seen  in  other  chronic  infections;    in 

some  instances  small  nontuberculous  abscesses  may  caseate.    Caseation 

is  sometimes  seen  in  serous  cavities :  e.  (^. ,  pericardium  or  pleura.     Rarely, 

'  "Deut.  Arch.  f.  klin.  Med.,"  1905,  Ixxxi,  p.  163. 


NECROSIS. 


^S5 


the  retention  of  mucoid  materials,  as  in  the  Fallopian  tubes,  may  be 
followed  by  inspissation  and  caseation. 

5.  Sphacelation  en  masse,  or  Gangrene.  This  process  is  also  known 
as  mortification.  A  sur^^^ical  term,  tiicrosis,  is  applied  to  death  of  bone 
en  masse.  Gangrene  or  mortification  is  the  death  of  any  tissue,  fol- 
lowed by  putrefaction,  while  attached  to  the  living  l)ody. 

Wirictics. — (a)  Moist  i^afitirciic,  which  is  further  divided  into  (/) 
circumscribed  anil  (j)  spreading:   (b)  dry  f:a)i(^rene:   (c)  hospital  f^ani^reue. 

(a)  Moist  gangrene  may  arise  from  disturbance  of  the  blood-supply 
— arrest  of  arterial  influx,  capillary  flow,  or  venous  exit.     Gangrene 


/ 


Fic.  145. — CoNFLUENXE  Of  T-.vo  TrnrRriE<; 
Hardened  in  corrosive  sublimate,  infiltrated  with   ■ 
balsam.     The  ma5s  has  originated  in  the  vt 
surround  adjacent  air  vr>l.  Ii  -■    ■■  md  c  hav. 
caseation.     .Ground  thr  .  a  zont  ./i  !> 

eccentrically  placi-d  Ki:ii  infritiucnt. 

.,    .!    iVir.u-  (onsidcrablc  '..  tuh  ..Li,-,  in. 


Ihr 


SErTi<iN  or  Lrsc. 


I.  .it  J.  ij  A  N^'liiATy  ijiant  lcU-     iudi 
which  leave  the  tubercle  mtm  at  a. 


mav  result  from  edcniu,    when  due  to  injury,  it  is  known  .1  :!i< 

gangrene;     when    caused   by   inflammation,   it    is   called    r  -rv 

gangrene.  The  inflammatory  processes  arresting  capillar\'  circulation, 
coagulation  necrosis  occurs. 'followed  by  gangrene.  The  cutting-off  of 
the  blood-supplv  may  result  from  occlusion  of  the  artery  by  an  em- 
bolus or  thrombus,  or  a  similar  obstruction  of  a  vein.  Continuous 
pressure  upon  an  area  bv  progressive  lessenmg  of  the  blood-supply 
leads  to  softening,  and  is  followed  by  infection  giving  rise  to  gangrene. 
Destruction  of  tissue  vitalitv  by  injury,  whether  traumatic,  chemic. 


256  GENERAL  PATHOLOGY. 

or  thermic,  leads  to  gangrene  if  putrefaction  occur.  Eichhorst^  has 
been  able  to  collect  166  cases  of  gangrene  associated  with  or  following 
infectious  disease.  In  65  cases  examined  at  autopsy  thrombosed  ar- 
terial trunks  were  found.  Ricketts  collates  134  cases  of  gangrene  in 
typhoid  fever;  varicella  gangraenosa  also  belongs  with  this  group.  The 
gangrene  occurring  in  infectious  diseases'  commonly  involves  a  number 
of  areas  {multiple  gangrene)  and  sometimes  affects  the  same  parts  on 
the  two  sides  of  the  body  {symmetric  gangrene).  Thayer's  studies  of 
arteritis  accompanying  infectious  diseases,  particularly  typhoid,  clearly 
indicate  the  character  of  the  lesion  (thromboarteritis  or  thrombophleb- 
itis) upon  which  the  gangrene  depends. 

Chronic  thrombosing  or  obliterative  endarteritis^  sometimes  termi- 
nates in  gangrene.  The  condition  is  occasionally  seen  in  the  young, 
and  differs  in  a  number  of  respects  from  arteriosclerotic  gangrene 
occurring  later  in  life  (see  Arteriosclerosis).  The  gangrene  produced 
by  obliterative  endarteritis  involves  particularly  the  extremities;  in 
the  case  reported  by  Morgan  all  the  limbs  were  affected  and  one  hand 
and  both  legs  were  amputated. 

Gangrene  in  all  its  forms  represents  death  of  the  tissue  involved, 
plus  infection.  In  the  absence  of  infection  mummification,  or  drying 
without  putrefaction,  occurs.  Such  a  condition  is  rarely,  if  ever  seen, 
certainly  not  in  masses  of  any  considerable  size.  The  odor  of  dry 
gangrene  is  significant  of  the  presence  of  bacteria.  In  spreading 
gangrene  a  violent  infection  occurs,  extending  by  the  lymphatics,  and 
with  such  rapidity  as  to  preclude  arrest  by  the  resources  of  the  tissues 
involved.  In  circumscribed  gangrene  the  process  is  limited  by  the 
protective  influence  of  the  body  juices  and  cells  and  extends  no  farther 
than  the  line  of  demarcation  described  below;  in  spreading  gangrene 
no  line  of  demarcation  is  formed.  The  infectious  processes  associated 
with  gangrene  are  not  fully  understood.  There  is,  however,  a  form 
of  spreading  gangrene — malignant  edema,  due  to  a  bacillus — that  has 
been  thoroughly  studied.     (See  Malignant  Edema,  p.  136.) 

Noma,  or  cancrum  oris,  is  a  gangrenous  process  that  attacks  the 
mucosa  of  the  mouth,  lips,  and  adjacent  structures.  (See  Diseases  of 
the  Alimentary  Canal,  Part  III.)  A  similar  if  not  identical  process  has 
been  observed  in  the  external  genitals,  particularly  in  the  female. 
The  affection  sometimes  manifests  an  epidemic  tendency,  especially 
where  large  numbers  of  children  are  congregated.  Blumer  and 
MacFarlane^  report  an  epidemic  of  16  cases.  Of  the  133  cases 
collated  by  Krahn,  55  followed  measles.  The  disease  is  practi- 
cally restricted  to  childhood,  but  occasionally  is  seen  in  debilitated 
adults,    particularly   consumptives,    and    those    recovering    from    such 

1  "Deut.  Arch.  f.  klin.  Med.,"  Bd.  Ixx,  H.  5  and  6.  See  also  Keen,  "Surgical 
Complications  and  Sequelae  of  Typhoid  Fever,"  1898.  Edwards,  "Archives  of 
Pediatrics,"  Aug.,  1903.  Ricketts,  "Cincinnati  Lancet-Clinic,"  Dec.  5,  1903. 
Auche  and  Laterrille,  "Jour,  de  Med,  de  Bordeaux,"  May  8,  1904.  Ley,  "Revue 
Francaise  de  Med.  et  de  Chir.,"  Oct.  10,  1904.  Rooth,  "Brit.  Med.  Jour.,"  Jan. 
24,    1903,   p.    197. 

=*  See  Michelis  and  Weber,  "Brit.  Med.  Jour.,"  Sept.  12,  1903,  p.  566.  Wulff, 
"Deut.  Zeit.  f.  Chir.,"  1901,  vol.  Iviii,  p.  47S.  Bunge,  "Arch.  f.  klin.  Chir.,"  1901, 
Bd.  63.  Beketoff,  "  Rousski  Vratch,"  1903.  Morgan,  "Jour.  Amer.  Med.  Assoc," 
Nov.   29,   1902,  p.   1359. 

'  "Amer.  Jour,  of  Med.  Sci.,"  Nov.,  1901.  See  also  von  Ranke,  "Mtinch. 
med.  Woch.,"   1903,  No.  i,  p.  13. 


NKCUOSIS.  257 

infectious  iliseases  as  typlioid.  Attempts  to  establish  a  spet-ific  microbe 
for  the  disease  have  been  un])ro(.luctive.  Clearly  the  atlection  is  poly- 
microbic in  a  larp;e  percentage  of  cases,  and  in  those  instances  in  which 
but  a  single  microbe  has  been  found  the  same  bacterium  is  not  always 
present.  In  Hlumcr  and  MacFarlane's  cases  and  in  the  instances 
stutlied  bv  Perthes,  von  Ranke,  and  a  few  others  a  leptothrix  was  ap- 
parently the  cause.  In  other  cases  the  diphtheria  bacillus,  staphylo- 
cocci, streptococci,  and  various  rod-shaped  and  s])iral  organisms  have 
been  found.  In  a  number  of  these  cases  the  diphtheria  bacillus  has 
been  the  onlv  organism  isolated.  The  bacillus  described  Vjy  Lingard 
is  present  in  a  small  percentage  of  cases.  Noma  is  fatal  in  from  fifty 
to  scvcntv  per  cent,  of  those  affected. 

Raynaud's  disease,'  or  digitu  mortui,  is  a  form  of  gangrene  due  to 
artenovascular  spasm.  Raynaud,  who  first  described  the  condition, 
called  it  gangrene  in  the  young,  thereby  distinguishing  it  from  the 
senile  and  diabetic  gangrenes  occurring  later  in  life;  it  is  not  restricted 
to  youth.  The  necrosis  is  frequently  multiple  and  symmetric,  affect- 
ing particularlv  the  lingers,  ears,  and  nose;  it  sometimes  occurs  in  the 
skin  of  the  trunk  and  extremities.  Osier  and  others  have  reported 
cases  tending  to  show  that  a  similar  vascular  spasm  may  occur  in  the 
viscera,  although  in  this  location  it  probably  never  goes  on  to  gangrene. 
In  practically  all  cases  studied,  changes  have  been  found  in  the  nerves 
or  vessels,  or  both.  The  condition  may  be  associated  with  acropar- 
esthesia, erythromelalgia,  sclerodactylia,  and  other  angioneurotic  dis- 
turbances. 

Morbid  Ajiatomy  of  Gan^i^rcnc. — The  tissues  involved  become  soft. 
pulp-like,  with  liquefaction  of  the  fat  and  cellular  elements;  as  this 
proceeds  blebs  form  upon  the  surface  and  discoloration  occurs — red- 
dish-purple, then  black,  with  varying  shades  of  green.  Putrefactive 
bacteria  gain  ingress  and  give  rise  to  the  chemic  phenomena  of  jjutre- 
f action.  Gases  may  be  produced,  and  these,  infiltrating  the  gangren- 
ous tissue,  give  rise  to  gangrenous  emphysema  or  gaseous  gangrene.* 
Some  cases  of  gangrene  manifest  gas  production  from  the  beginning, 
and  in  others  the  phenomenon  appears  late ;  in  many  instances  gas  pro- 
duction does  not  occur,  and  the  interstitial  evolution  of  gas  is  practic- 
allv  never  present  in  the  so-called  dry  gangrene.  The  blooil-celN  fragment 
and  discolor  the  fluids,  which  may  be  extruded  through  the  skin.  The 
gases  of  putrefaction  give  rise  to  the  horribly  fetid  odor  at  times 
present.  Where  the  gangrenous  mass  joins  the  living  tissue,  a  line  of 
demarcation  occurs;  this  line  represents  the  point  at  which  the  tissue 
is  viable,  and  where  tissue  death  and  the  processes  of  infection  are  ar- 
rested, although  some  of  the  chemic  agents  elaborated  below  this  point 


'  The  literature  of  the  subject  mav  be  traced  from  the  foUowinir  articles: 
Savill.  •Lancet."  June  i,  1901.     Osier,  "Bull,  of  Johns  Hopkins  Ho  •   ■    '       •    < 
1900.      Dekcyser,  '"  jour.  M^d.  Bnixelles."  Nov.  i,?.  1902.  p.  7J5.     LyL 
■Phila.  Med.  Jour..'"  Aug.  10.  1901.      Kr-        \-      •     ^'^  •'        \l  .      . - 
Brit.  Med.  lour.."  March  21,  1903,0.  ' 

'  Legros."  -Recherches  Bact.  s.  1.  Gan;, 
saucr.   'Munch,  mcd.  VVoch.,"  Sept.  8,    1903        kisl.      An.ter..Ue;>  I 
Suppurations  Gangrcneuses."  "Bulletin  dc  llnst     Pasteur.  "  Jan    ' 
Sappington,    "N.  Y.  Med.  Jour.."   April   3.   100.4.  p.  641.     Kat;  i 

Bakt.."  Feb.   18.  1004.   Bd.  xxxv.  No.  5.  p.   5v»       Dudgeon  an  th 

Soc.  of  London."  Jan.  19,  1904. 
18 


258  GENERAL   PATHOLOGY. 

may  be  absorbed.  At  this  line  of  demarcation  embryonic  tissue,  followed 
by  granulation  tissue,  develops;  these,  progressing  from  the  surface, 
separate  the  dead  from  the  living  tissues ;  in  the  soft  parts  this  separation 
advances  with  considerable  rapidity,  while  in  bone  the  progress  is  much 
slower.  In  the  dead  tissue  putrefaction  proceeds  exactly  as  it  would 
if  the  tissue  were  separate  from  the  body;  advanced  autolytic  and 
liquefactive  changes  occur  in  the  cells,  which  eventually  liquefy.  The 
gases  produced  are  compounds  of  hydrogen,  sulphur,  ammonium,  etc. 

During  the  destructive  metabolism  of  tissue,  induced  and  carried 
on  by  bacteria,  in  addition  to  the  products  already  mentioned  are 
certain  chemic  bodies  always  the  essential  result  of  microbic  growth 
— ptomains.  These,  for  the  most  part,  are  highly  diffusible,  and  are 
rapidly  absorbed  by  the  living  tissues,  and,  entering  the  circulation, 
give  rise  to  the  systemic  symptoms  of  gangrene.  It  is  possible  to 
understand  how  the  intensity  of  the  symtoms  depends  upon  the  amount 
of  poison  generated  in  the  gangrenous  focus,  the  rapidity  of  its  absorp- 
tion, and  the  resistance  of  the  patient. 

In  spreading  gangrene  the  infection  promises  to  be  rapidly  fatal 
by  its  quick  spread  and  the  extreme  activity  of  the  toxic  substances 
produced  and  absorbed;  hence,  the  surgeon  lays  great  stress  upon  the 
necessity  of  immediate  removal  of  the  structures  in  which  infection  is 
advancing.  The  urgency  of  the  case  is  augmented  by  the  fact  that 
no  line  of  demarcation  occurs.  In  circumscribed  gangrene  the  bac- 
teria present  may  not  be  able  to  invade  the  adjacent  normal  tissues 
possessing  their  usual  degree  of  resistance.  In  spreading  gangrene, 
however,  the  evidence  would  seem  to  indicate  that  the  tissue  resistance 
must  be  reduced  or  that  the  bacteria  possess  the  power  of  infiltrating 
and  destroying  tissue  not  previously  injured.  By  some,  spreading 
gangrene  is  believed  to  be  an  infection  of  the  lymph-spaces,  along  which 
the  bacteria  travel,  elaborating  their  poisons,  which,  in  turn,  destroy 
the  adjacent  tissue. 

(b)  Dry  gangrene  differs  from  the  preceding  in  that  the  less  juicy 
nature  of  the  tissues  involved  resists  infection  and  the  dead  structures 
manifest  a  marked  tendency  to  mummification.  It  commonly  results 
from  atheroma  or  obliterative  changes  in  the  blood-vessels  supplying  the 
part.  The  skin  being  unbroken,  there  is  little  tendency  toward  infection 
and  consequent  putrefaction.  It  is  associated  occasionally  with  diabetes 
and  other  adynamic  states  in  elderly  people  having  the  vascular  lesions 
already  noted.  It  is  spoken  of  as  senile  gangrene  and  as  diabetic  gan- 
grene under  the  conditions  just  named. 

(c)  Hospital  gangrene  is  now  a  historic  disease,  modern  antisepsis 
having  led  to  its  disappearance.  It  probably  represented  an  infection, 
of  extreme  virulence,  the  exact  nature  of  which  may  be  surmised  only. 


»57 


CHAPTER  X. 

CIRCULATORY     DISTURBANCES. 

Anemia.  ^The  term  anemia  is  used  lu  designate  certain  changes 
in  the  blood  by  which  its  functional  activity  is  lessened;  but,  as  here 
considered,  reference  is  made  to  the  local  anemia  dependent  upon 
changes  influencing  the  circulatory  apparatus,  and  not,  essentially,  upon 
alterations  in  the  blood  itself;  it  is,  therefore,  an  ischemia. 

Cait.scs. — (i)  Faulty  distribution  of  the  blood,  as  in  shock,  when 
the  blood  tends  to  accumulate  in  the  larger  veins,  particularly  the 
splanchnic  veins.  (2)  A  very  much  weakened  circulation,  whether 
due  to  shock,  disease,  or  the  influence  of  poisons,  may  be  too  feeble 
to  force  the  blood  through  the  capillary  system,  particularly  in  the  skin 
and  brain;  hence,  cerebral  anemia  and  cutaneous  anemia  may  arise. 
(3)  Diseases  of  the  blood-vessels,  such  as  atheroma;  obliterating  in- 
flammation of  an  arterv  leads  to  lessened  blood-supply  in  the  distribu- 
tion of  the  affected  vessel.  (4)  Pressure.  (5)  Occlusion  of  an  artery, 
whether  complete  or  partial,  as  by  ligature,  pressure  of  a  tumor,  throm- 
bosis, or  embolism.  (6)  Spasm  of  the  blood-vessel,  due  to  contraction 
of  its  muscle-fibers,  either  dependent  upon  or  independent  of  the  inner- 
vation. (7)  An  abnormal  perivascular  pressure  in  the  area  involved 
mav  lessen  the  possible  ingress  of  blood.  This  increased  perivascular 
I)re'ssure  mav  arise  in  a  number  of  ways.  Organizing  cicatricial  tissue 
may,  bv  its  contraction,  so  increase  the  pressure  normally  exerted  upon 
the'  capillaries  that  the  blood  flow  may  be  greatly  diminished  or  even 
obliterated  in  some,  if  not  all,  of  the  capillaries  of  the  area  involved. 

Morbid  Anatomy.— The  area  is  pale  and  bloodless,  and  the  tem- 
perature is  likelv  to  be  lower  than  normal,  or.  when  the  general  body- 
temperature  IS  above  the  normal,  the  anemic  area  manifests  a  less 
marked  elevation;  there  may  be  some  edema,  and,  as  will  be  seen  later. 
the  stagnation  of  regurgitation  may  be  evident. 

Efjcct.—li  the  ischemia  be  temporary,  there  is  but  slight  interference 
with  function;  if  the  process  be  slowly  developed,  a  gradual  lessening 
of  function  occurs,  and  the  area  may  undergo  degenerative,  necrotic. 
or  atrophic  changes;  the  same  result  may  follow  a  slight  anemia  that 
persists.     If  the  local  anemia  be  suddenly  developed    and  the  blood- 
supplv  is  insufftcient  to  maintain  nutrition,  death  of  the  part  may  ensue; 
such  a  condition  sometimes  follows  ligation  of  the  mam  artery  of  a  limb. 
Local  anemia  lessens  the  functional  activity  of  the  tissues  invo! . 
diminishes  their  reparative  power  and  resistance  to  infprtion      It 
be  greatly  reduced  or  abolished,  even  for  a  short  time 
take  place  in  the  capillary  walls  which  increase  tlf 
favor  the  formation  of  exudates,  and  sometimes  capillary 
upon  the  re-entrance  of  blood  or  there-establishment  <>f  tli. 

250 


26o  GENERAL  PATHOLOGY. 

or  after  the  occurrence  of  satisfactory  collateral  anastomosis.  Vascular 
spasm,  lessening  the  blood-supply  to  an  area,  is  usually  associated  with 
pain,  which  is  most  marked  at  the  point  of  vessel  constriction;  at  the 
same  time  there  occurs  more  or  less  muscle  spasm,  rendering  volun- 
tary movement  of  the  affected  part  difhcult  and  often  painful.  The 
pain  of  angina  pectoris,  due  to  coronary  artery  disease,  the  alDdominal 
pains  of  arteriosclerosis,  and  the  lancinating  pains  due  to  sclerotic  ves- 
sels in  the  lower  extremities  appear  to  be  of  ischemic  origin.  Vas- 
cular spasm,  when  involving  the  leg,  and  attended  by  muscular  cramps, 
has  been  called  intermittent  laming  or  intermittent  claudication. 

If  the  arrest  of  the  blood-supply  occur  in  an  artery  supplied  bv  a 
branch  that  communicates  indirectly  with  the  area  involved,  and  the  cir- 
culation be  turned  through  the  branch  to  supply  nourishment  in  the  indi- 
rect route  indicated,  such  a  process  is  spoken  of  as  collateral  anastomosis. 
With  the  occlusion  of  an  artery  the  blood-pressure  beyond  the  ob- 
struction gradually  lessens  until  a  point  is  reached  when  it  is  less  than 
the  pressure  in  the  veins.  Backward  distention  may  now  occur,  so 
that  an  area  which  at  one  time  showed  marked  ischemia  later  becomes 
distended  by  venous  blood.  This  constitutes  the  stagnation  of  regurgita- 
tion, and  probably  ends  in  infarction.     (See  Embolism.) 

Ischemia  is  sometimes  said  to  be  collateral  or  compensatory  when 
it  results  from  the  accumulation  of  blood  elsewhere. 

Hyperemia  {''Active  Hyperemia''  or  ''Active  Congestion  of  Some 
Authors). — This  condition  is  dependent  upon  an  increased  arterial 
influx,  a  distention  of  the  capillaries  by  arterial  blood,  and  hence  is  called 
arterial  hyperemia,  in  contradistinction  to  a  condition,  to  be  considered 
later,  in  which  the  blood  present  is  essentially  venous. 

Catises. — (i)  Physiologic,  as  the  hyperemia  of  the  mucous  mem- 
branes during  digestion  or  of  the  uterine  muc9sa  during  menstruation. 
(2)  In  inflammation,  hyperemia  constitutes  the  first  stage,  and  usually 
persists  during  the  activity  of  the  processes.  (3)  Increased  arterial 
pressure  or  tension;  ordinarily,  it  is  probable  that  the  greater  quantity 
of  the  blood  is  in  the  venous  system,  but  when  there  is  increased  cardiac 
activity,  the  arterial  and  arteriocapillary  systems  become  surcharged; 
examples  of  this  are  seen  in  the  flushed  face  of  active  exercise  and  in 
the  apoplexy  that  follows  violent  exertion.  (4)  Neuroparalytic,  when 
the  stimulus  to  the  vasoconstrictors  is  withdrawn.  (5)  Neurotonic, 
when  there  is  hyperactivity  of  the  vasodilators.  (6)  Local  anemia 
is,  at  times,  quickly  followed  by  a  more  or  less  marked  arterial  hyperemia. 
Thus,  prolonged  pressure  not  uncommonly  produces  active  hyper- 
emia in  the  affected  area.  A  similar  hyperemia  is  seen  to  follow  the 
removal  of  Esmarch's  bandage,  applied  for  the  purpose  of  preventing 
hemorrhage  during  the  progress  of  operations.  The  local  anemia  pro- 
duced by  cold  is  frequently  followed  by  an  arterial  hyperemia.  (7)  A 
sudden  stroke  applied  to  the  skin  is  quickly  succeeded  by  a  local  hyper- 
emia, probably  depending  upon  a  temporary  paralysis  of  the  vaso- 
constrictors. (8)  Certain  chemic  bodies  also  induce  hyperemia:  e.  g., 
mustard,  chloroform,  cantharides,  etc.  These  probably  act  by  induc- 
ing inflammation, — in  other  words,  as  irritants, — and  the  result  should 
therefore  be  considered  with  inflammatory  hyperemia.  Hyperemia 
is  said  to  be  compensatory  and  collateral  when  the  blood  is  forced  into 
one  area  by  reason  of  its  inabilitv  to  enter  another,  or  as  the  result  of 


(  IIUUI.ATORY    DISTURBANCES.  261 

anemia  elsewhere ;  siuli  a  eondition  is  observed  in  the  increased  amount 
of  blood  sent  to  one  lunj^  when  the  other  is  solid  or  conipresse<l. 

Morbid  Aiiato)ny. — During  life,  redness,  increased  cellular  activity, 
and  usually  a  slightly  elevated  temperature  are  manifest;  swelling, 
discomfort,  and,  ])erhaps.  pain  may  accompany  the  condition;  if  the 
process  is  physiologic,  the  functional  activity  is  usually  increased; 
in  pathologic  hyjieremia  inflammation  is  likely  to  occur.  Persistent 
physiologic  hyperemia  may  lead  to  hypertrophy;  similar  patlK^logic 
hyperemia  may  cause  some  of  the  degenerative  processes  already  de- 
scribed. Postmortem,  as  the  result  of  emptying  of  the  arterioles  and 
capillaries,  the  evidence  of  hyperemia  may  be  wanting.  Microscopi- 
cally, however,  there  will  usually  be  found  capillary  rhexis.  and.  if  the 
process  has  persisted,  degenerative  or  inflammatory  changes  may  have 
ensued. 

Plethora,  also  known  as  polyemia  and  repletio,  implies  an  abnormal 
fullness  of  the  entire  vascular  a])paratus.  Several  forms  have  been 
described,  dependent  upon  the  material  that  is  increased  in  the  blood, 
whether  it  be  an  excess  in  the  water,  in  the  albuminous  compounds, 
or  in  the  corpuscular  elements. 

Thoma  speaks  of  a  plethora  vera,  in  wliicli  the  lilnrxl  ])resent  is  ncjr- 
mal  but  the  total  volume  is  increased;  hydremic  plethora,  as  dependent 
upon  an  additional  quantity  of  water;  again,  when  the  |)lcth(>ra  seems 
to  involve  the  entire  vascular  system,  it  is  said  to  be  a  general  plethora  ; 
a  localized  form  is  described  that  is  analogous  to  congestion,  l)Ut  is  some- 
times called  vascular  plethora.  An  overdistention  of  the  lymph-spaces 
is  spoken  of  as  lymphatic  plethora,  a  condition  closely  allied  to  edema. 
(See  also  chapter  on  The  Blood.  Fart  III.) 

Hemorrhage. — The  escape  of  all  the  constituents  of  the  blood  con- 
stitutes what  is  ordinarily  spoken  of  as  a  hemorrhage.  Hemorrhages 
are  said  to  be  arterial,  venous,  capillary,  or  mixeJ,  depending  upon  the 
vessel  or  vessels  from  which  the  bleeding  occurs.  The  escape  of  blood 
as  a  result  of  solution  in  the  continuity  of  the  blood-vessels  is  called 
Jiemorrliage  per  rhexin.  The  hemorrhages  that  arise  as  a  result  of 
trauma  are  properlv  to  be  classified  with  this  group.  The  injury  to 
the  vessel  may  not  be  sufficient  to  permit  the  escape  of  blood  at  once. 
but  later  degenerative,  necrotic,  or  inflammatory  change,  attacking 
the  vessel  wall,  mav  cause  it  to  rupture.  Increaseii  arterial  tension 
is  also  said  to  be  a  cause  of  hemorrhage.  It  is  ])robable,  however,  that 
the  normal  blood-vessel,  whether  it  be  artery,  capillary,  or  vein,  not 
previously  injured  or  diseased,  never  ruptures  as  the  result  of  a  sim:iU' 
rise  in  the  blood-pressure.  Developing  blood-vessels  may  be  ex.. -p- 
tions  to  this  rule.  When  a  hemorrhage  occurs  from  a  blood-vessel  (cap- 
illary or  vein)  without  manifest  solution  in  the  continuity  of  its  wall. 
the  condition  is  spoken  of  as  hemorrhage  per  diapedcsin.  Such  hen..: 
rhage  occurs  as  a  result  of  venous  obstruction.  The  incre.i  •  • 
permeability  of  the  blood-vessels  is  largely  induced  through  interfen  •  • 
with  their  nutrition,  as  after  persistent  local  anemia,  or  as  a  result  ..i 
injury,  mechanical  or  thermic,  as  well  as  chemic;  including  under  the 
last-named  the  destructive  influences  manifested  upon  the  vascular 
endothelium  bv  the  poisons  of  many  l)actena. 

As  illustrating  the  influences  of  bacteria  and  bacten 
the  production  of  capillar)'  hemorrhage,  the  cutaneous. 


262  GENERAL  PATHOLOGY. 

submucous  hemorrhages  of  septicemia,  cholera,  yellow  fever,  and  allied 
diseases  may  be  cited.  It  seems  probable  that  rheumatism  is  a 
bacterial  affection,  and,  if  so,  the  capillary  hemorrhages  present  in  the 
disease  called  purpura  rheumatica  may  be  of  infectious  origin.  With 
this  group  should  be  considered  the  so-called  hemorrhagic  septicemias. 
These  are  seen  particularly  in  animals,  but  there  can  be  no  doubt  that 
essentially  the  same  condition  occurs  in  man.  It  is  well  knowm  that  a 
number  of  bacteria  produce  hemolytic  poisons,  and  that  blood  in  which 
hemolysis  is  in  progress  escapes  the  endothelium  of  the  vessels  more 
readily  than  in  health.  Grenet^  suggests  that  purpuric  affections  are 
produced  by  the  action  of  toxic  substances  on  the  liver.  The  toxic 
nature  of  such  hemorrhages  is  further  shown  by  their  most  frequent 
occurrence  in  connection  with  infectious  diseases.  Blair-  has  col- 
lected a  number  of  cases  of  typhoid  with  multiple  subcutaneous  hemor- 
rhages. Tripp  ^  has  observed  purpuric  hemorrhages  in  ptomain  poison- 
ing. The  frequent  occurrence  of  mucous,  submucous,  serous  and  sub- 
serous, and  cutaneous  hemorrhages,  in  leukemia,  particularly  toward 
the  end  of  the  disease,  shows  the  influence  of  blood  alterations  in  pro- 
ducing the  condition.  Wollstein*  believes  that  the  hemorrhagic  affec- 
tion occurring  in  the  new-born,  and  called  morbus  maculosus  neona- 
torum, epidemic  hemoglobinuria,  acute  fatty  degeneration,  syphilis 
haemorrhagica  neonatorum,  and  by  other  names,  is  an  infection  not 
attributable  to  any  specific  organism,  but  may  be  produced  by  the 
Staphylococcus  pyogenes  albus  or  aureus,  the  pyogenic  streptococci, 
pneumococcus.  Bacillus  pyocyaneus.  Bacillus  hsemorrhagicus,  the  Bacil- 
lus coli  communis  the  Bacillus  enteritidis  (Gartner),  and  possibly  other 
organisms  The  condition  may  occur  in  syphilitic  infants  independently 
of  any  other  infection.  The  extensive  ecchymoses  that  occur  in  phos- 
phorus-poisoning are  probably  brought  about  by  alterations  in  the 
blood  and  by  degenerative  changes  in  the  capillary  walls.  A  similar 
explanation  is  probably  operative  with  regard  to  the  capillary  hemor- 
rhages induced  by  the  poison  of  venomous  reptiles.  The  presence  of 
bile  in  the  blood  is  often  associated  with  an  increased  tendency  to 
hemorrhage;  wounds  in  jaundiced  patients  often  bleed  profusely  and 
stubbornly  resist  the  usual  methods  of  hemostasis.  Robson  believes 
that  the  tendency  to  hemorrhage  in  jaundice  is  intensified  by  the  presence 
of  associated  pancreatic  disease. 

In  addition  to  the  morbid  conditions  just  considered, — in  which  it 
would  appear  that  the  occurrence  of  hemorrhage  was  dependent  upon 
an  acquired  alteration  in  the  blood  or  blood-vessel,  or  in  both,  and  hence 
called  an  acquired  hemorrhagic  diathesis, — -we  occasionally  find  individ- 
uals possessing  an  extraordinary  tendency  toward  the  occurrence  of 
severe  hemorrhage  resulting  from  the  most  trivial  cause,  which  ten- 
dency seems  to  have  been  transmitted  from  ancestors  who  manifested 
the  same  peculiarity.  Such  a  condition  is  called  inherited  hemorrhagic 
diathesis,  or  hemophilia.^     Hemophilia,  or  bleeding  diathesis,  is  trans- 

^  These  de  Paris,   1905. 

^  "Lancet,"  Jan.  14,  1905,  p.  84. 

^  "Northwestern  Medicine,"  June,  1903. 

*  "Arch,  of  Paediatrics,"  Sept.,  1904. 

^  Velliet,  "Revue  de  la  Med.  Swiss.  Romain,"  Dec.  20,  1902.  Carless,  "Prac- 
titioner," 1903,  vol.  Ixx,  p.  S5.  Grant,  "Lancet,"  Nov.  5,  1904.  p.  1279.  Greir, 
"  Medizinskoe  Oborenie,"  Ixi,  No.  i.  Lossen,  "Deut.  Zeit.  f.  Chir.,"  1905,  vol. 
Ixxvi,  p.  I. 


CIUCULATOKY    DISTURBANCES.  363 

mitted  commonly  from  the  mother;  as  n  rule,  the  male  children  mani- 
fest the  disease  but  do  not  transmit  it.  The  female  children,  '»n  the 
other  hand,  usually  show  no  evidence  of  the  affection,  but  transmit 
it  to  their  children.  No  satisfactory  explanation  has  l)een  offcreil  for 
this  congenital  hemorrhagic  diathesis,  although  cases  undoubt«"i' 
occur  in  which  the  hemorrhages  arc  arrested  by  tlie  application  of  a;-  •  • 
favoring  the  coagulation  of  the  blood.  Wright'  has  shown  thai  in 
some  "bleeders"  the  calcium  content  of  the  blood  is  below  normal. 

Genealogic  Tree  of  a  Hemopiiimc  Family.' 

(The  persons  affected  arc  indicated  by  an  •  ) 


M* 


M  M 


F*  F 

I  I 

I  M*  I'* 

i 

I  Daughters  Sons* 


M  M*  M* 

In  addition  to  the  dangers  from  traumatic  hemorrhage,  hemophiliacs 
occasionally  manifest  a  tendency  toward  other  forms  of  bleeding 
for  which  no  adequate  explanation  at  present  can  be  given.  This 
})eculiarity  is  sometimes  shown  by  the  occurrence  of  hemorrhage,  which 
may  be  fatal,  from  a  kidney  apparently  normal  even  when  submitted 
to  careful  microscopic  examination  (causeless  hematuria).  Less  com- 
monly the  hemorrhage  without  discernible  anatomic  lesions  is  from 
the  stomach  or  intestines.  Hemarthrosis  in  hemophiliacs  has  been 
especially  studied  by  Konig,  Lucas,  Carless,  Broca  and  others.  Poillct 
has  analyzed  252  cases;  the  affected  joints  are  first  distended  with 
blood,  followed  by  ecchymosis  in  the  para-articular  and  subcutaneous 
tissues.  The  blood  is  promptly  al)sorbed,  but  the  bleeding  recurs,  and 
eventually  the  synovial  membranes  thicken,  the  fringes  hypertrophy, 
and  the  articular  cartilages  become  lipped  at  their  free  margin  and  at 
points  pitted.  The  affection  occurs  chiefly  between  the  fourth  and  sixth 
years  of  life,  nearly  all  the  patients  are  males,  and  nearly  all  the  cases 
that  have  been  operated  upon  died.  The  knee  is  affected  in  abn'!* 
fifty  per  cent.,  and  the  elbow  in  about  twenty-tive  j)er  cent,  of  the  <  ;i  • 

When  inflammatory,  suppurative,  infectious,  or  ulcerative  pro*  t 
approach  the  blood-vessel  from  without  and  destroy  its  walls,  the  • 
sequent  hemorrhage  is  spoken  of  as  Iwmorrhaiic  hyJial'  r  lurmor- 

rliagc  per  diabrosin.     Such  hemorrhages  occur  from  bh  'Is  in  the 

cavities  resulting  from  pulmonary  tuberculosis  and  occasionally  are  due 
to  suppurative  processes  around  the  large  vascular  trunks  of  the  neck 

The  influence  of  the  nervous  system  in  the  production  of  hemor- 
rhage  is   but   little   understood.     It    may    act   indirectly   thrn-- •'■    ''^ 
vasomotor  system,  raising  the  arterial  ten.sion  and  increasing  ■ 
sure  in  diseased  blood-vessels  that  are  already  taxed  to  withstatia  inc 

'  "  Lancet."  July  5.  1902.  p.  15. 

'Quoted  by  Lazarus- Barlow  from  "Schmidt's  Jahrbucher,"  etc.,  1863,  vol. 
cxvii,  p.  330. 


264  GENERAL  PATHOLOGY. 

normal  stress,  and  hence,  under  the  increased  pressure,  give  way. 
Such  action  of  the  nervous  system  fails  to  explain  hemorrhage  from 
the  stomach  <and  intestines  in  diseases  of  the  crura  cerebri,  and  the 
occasional  instances  of  vicarious  menstruation  manifested  by  hemor- 
rhages from  the  nose,  mouth  lungs,  etc.  The  hemorrhages  of  hysteria 
would  seem  properly  to  be  classed  with  this  group. 

Small  areas  of  hemorrhage  with  sharply  defined  margins,  at  first 
red  then  purplish,  and  eventually  purplish-black,  are  known  as  pete- 
chicB.  Purpuric  hemorrhages  manifest  themselves  by  numerous  petechiee 
principally  in  the  submucous  or  subcutaneous  structures;  they  are 
also  occasionally  observed  under  serous  membranes.  An  ecchymosis  is 
a  submucous,  interstitial,  or  subcutaneous  hemorrhage,  commonly  due 
to  injury,  but  also  arising  from  other  causes.  Extensive  infiltration 
of  the  connective  tissues  by  blood  is  spoken  of  as  hemorrhagic  infiltra- 
tion, or  bloody  suffusion,  or  suggillation.  When  blood  collects  so  as  to 
form  a  distinct  tumor,  the  mass   is  called  a  hematomu. 

Hemorrhages  from  various  cavities  and  surfaces  have  received  special 
names,  depending  upon  their  location  or  on  the  phenomena  to  which 
they  give  rise:  hemorrhage  from  the  nose  is  called  cpistaxis;  hemor- 
rhage from  the  lungs,  bronchopulmonary  hemorrhage,  or  hemoptysis; 
excessive  menstrual  flow  is  menorrhagia,  and  uterine  hemorrhage  oc- 
curring independently  of  menstruation,  metrorrhagia;  bleeding  from 
the  bowels,  enterorrhagia  or  intestinal  hemorrhage;  hemorrhage  from 
the  urinary  organs  (the  blood  being  voided  with  the  urine),  hematuria; 
hemorrhage  into  joints,  hemarthron  or  hemarthros ;  hemorrhage  into  the 
brain,  cerebral  hemorrhage,  cerebral  apoplexy,  or  hematencephalon ;  blood 
in  the  pleural  cavity,  hemothorax ;  a  collection  of  blood  in  the  pelvic 
peritoneum  or  in  the  tunica  vaginalis  testis  is  spoken  of  as  a  hematocele ; 
hemorrhage  into  the  central  canal  of  the  spinal  cord,  hematomyelia ; 
hemorrhage  into  the  pericardium,  hemo pericardium;  hemorrhage  into 
the  peritoneum,  hemo  peritoneum;  and  so  on. 

The  effects  of  hemorrhage  may  be  local  or  constitutional.  The  local 
changes  to  be  considered  are  only  those  that  arise  in  connection  with 
accumulations  of  blood  that  remain  in  contact  with  the  living  tissues. 
Blood  acted  upon  by  the  digestive  juices  is  more  or  less  modified  by 
the  chemic  changes  which  they  induce.  In  the  stomach  it  forms  a 
brown  or  brownish-black,  grumous  substance,  resembling  coffee-ground; 
hence  the  term  "coffee-ground  vomit,"  used  to  designate  the  vomiting 
of  more  or  less  altered  blood.  Within  the  intestinal  canal  the  altera- 
tion is  more  marked  when  hemorrhages  have  occurred  sufficiently  high 
to  permit  prolonged  contact  with  the  intestinal  juices.  The  blood  of 
rectal  hemorrhage  may  escape  with  but  little  alteration.  When  hemor- 
rhages arise  in  the  upper  intestine  the  blood  is  usually  converted 
into  a  tarry  substance.  Blood  thrown  out  into  the  serous  cavities  or 
interstitial  tissues,  unless  excessive,  is  usually  absorbed. 

The  fate  of  hemorrhages  into  the  connective  tissues  is  largely  de- 
pendent upon  the  amount  of  blood  extravasated  and  upon  the  dam- 
age to  which  the  tissue  has  been  subjected.  When  the  hemorrhages 
are  small  the  blood  rapidly  undergoes  hemolysis,  the  red  corpuscles  yield 
their  hemoglobin  and  fragment,  and,  eventually  dissolving,  the  resulting 
products  are  carried  away  by  the  lymphatics.  The  display  of  color  that 
occurs  in  bruised  areas  or  areas  of  local  hemorrhage  is  dependent  upon 


CIRCULATOKY    OIST  U  R  UvVNCES.  ,1,:, 

alterations  in  the  hemoglobin  Distinct  collection^  ni  i-k.om  [,i. m.ito- 
mata),  if  still  communicating  with  an  artery,  may  remain  as  false  aneu- 
rysms. (See  Aneurysms.)  The  small  amount' of  infiltration  at  the 
periphery  of  a  blood  collection  is  replaced  by  cicatricial  tissue,  which, 
with  the  condensed  structures,  forms  a  false  wall;  this  structure  may 
limit  the  hemic  tumor  or  may  gradually  yield  and  eventually  rupture. 
Similar  collections,  not  communicating  with  an  arterv,  usually,  in  time, 
undergo  complete  absorption;  sometimes,  however,  such  a  mass  is  walled 
oflf  by  a  newly  formed  connective-tissue  membrane,  which  may  become 
calcareous;  in  time,  this  may  contract  and  eventually  leave  nothing 
but  an  area  of  induration.  Small  residual  collections  of  unabsorbed 
blood  may  undergo  calcareous  change. 

The  systemic  phcuomctia  induced  by  liemorrlia(^e  are  dependent  U[)on 
the  amount  of  blood  lost  and  upon  the  rapidity  with  which  it  escapes. 
A  considerable  quantity  of  blood  may  be  lost  by  a  slowlv  oozing  hemor- 
rhage without  giving  rise  to '  any  consi)icuous  symj)tom.  A  much 
smaller  quantity,  however,  suddenly  ejected  by  an  arten*',  mav  induce 
a  rapidly  fatal  issue.  In  severe  hemorrhage  the  blood-pressure  begins 
to  fall  coincident  with  the  blood  loss.  This  fall  in  vascular  tension  lessens 
the  amount  of  blood  that  will  escape  (in  the  same  length  of  time  under 
higher  blood-pressure  the  loss  would  be  greater),  and  favors  the  occur- 
rence of  coagulation,  at  the  same  time  permitting  contraction  of  the 
blood-vessel.  The  sudden  drop  in  blood-pressure,  and  the  associated 
faulty  distribution  of  the  blood,  give  rise  to  cerebral  anemia,  which, 
if  the  fall  be  marked  or  long  continued,  may  terminate  fatally.  Under 
lower  blood-pressure  a  clot  not  uncommonly  forms  in  the  wounded 
vessel,  and  with  the  complete  arrest  of  hemorrhage  the  volume  of 
blood  is  made  up  as  soon  as  possible  by  removal  from  the  lymph-spaces 
of  the  available  fluid  in  the  body,  gradually  restoring  the  circulatory 
volume  and  paving  the  wav  to  complete  regeneration  of  the  blood. 
(See  Blood.) 

Lymphorrhea  or  lymphorrhagia  is  the  abnormal  escape  of  lymph, 
usually  due  to  some  solution  in  the  continuity  of  the  larger  lymph- 
vessels.  The  same  term  is  made  to  embrace  the  escape  of  chyle  from 
the  lacteal  system  or  thoracic  duct,  a  condition  usually  due  to  the 
injury  of  these  structures  or  to  the  presence  of  thrombosis  or  an  animal 
parasite  occluding  the  lumen.'  Wounds  or  rupture  of  the  thoracic 
duct  may  permit  the  chyle  to  enter  the  peritoneum  (chylous  ascites) 
or  pleura  (chylothorax). 

The  condition  which  I  shall  describe  as  congestion  is  also  known 
as  venous  hyperemia  or  venous  couf^estion,  passi'ee  hyperemia  or  passive 
coni^estion.  It  results  from  faulty  exit  of  the  blood,  and  consequent 
retarded  flow,  giving  ri.se  to  accumulation  in  the  veins  and  capillaries 
of  the  area  involved.  In  contrast  to  hyperemia,  in  which  there 
is  an  increased  amount  of  arterial  blood,  in  congestion  there  is  an  in- 
creased amount  of  venous  blood. 

Causes. — Any  condition  that  prevents  free  venous  exit,  and  that 
at  the  same  time  does  not  limit  arterial  ingress;  pressure,  and  con- 
stricting bands  that  compress  the  easily  collapsed  veins  and  not  the 
more  rigid  arteries;  diseases  of  the  veins,  such  as  inflammation  and 
thrombosis,  which  narrow  the  lumina  and  lessen  the  carrying  capacity 
'  See  Elephantoid  Diseases,  p.  210 


266  GEXERAL  PATHOLOGY. 

of  the  affected  vessels;  tumors,  and  pressure  from  surrounding  or 
adjacent  organs  or  structures.  In  a  feeble  circulation  congestion  is 
favored  by  the  influences  of  gravity,  as  in  the  congested  extremities 
of  individuals  suffering  from  valvular  heart-disease.  Venous  and 
capillary  distention,  dependent  upon  feebleness  of  the  circulation,  is  illus- 
trated in  the  hypostatic  congestion  of  the  lungs  that  accompanies 
typhoid  fever  and  other  adynamic  states.  Arrest  of  arterial  flow 
may  lead  indirectly  to  congestion  depending  upon  the  regurgitation 
of  blood  from  veins  in  which  a  more  or  less  constant  pressure  is 
maintained;  such  vascular  distention,  at  first  manifested  in  the 
larger  veins,  but  sooner  or  later  reaching  the  '.-enules  and  capillaries, 
is  termed  the  congestion  of  regurgitation. 

Morbid  Anatomy. — This  is  largely  dependent  upon  the  duration 
of  the  process  and  its  magnitude.  During  life  the  area  involved  is 
edematous,  swollen,  and  bluish,  with  a  temperature  usually  lower  than 
normal.  The  cause  of  the  associated  swelling  will  be  further  considered 
when  dealing  with  edema.  The  gradual  reduction  in  circulatory  activity 
gives  rise  to  overdistention  of  the  capillaries  of  the  area  involved, 
degenerative  changes  in  their  walls,  and,  if  prolonged  or  intense,  dia- 
pedesis,  and  corpuscular  plugging.  The  distention  of  the  capillaries 
by  plugs  in  which  the  cellular  elements  may  no  longer  be  recognized 
(stasis)  is  frequently  seen.  As  a  result  of  hemolysis  affecting  the  quies- 
cent red  blood-cells,  both  within  and  without  the  blood-vessels,  a 
certain  amount  of  pigmentation  may  be  present,  particularly  where 
the  process  has  been  long  continued.  Prior  to  complete  stagnation 
and  dissolution  of  the  cellular  elements  restoration  of  the  circulation 
is  possible.  The  process  is  likely  to  terminate  in  degenerative,  atrophic, 
or  necrotic  changes  in  the  affected  tissues;  this  is  due  to  the  fact  that 
nutrition  in  any  given  area  is  as  dependent  upon  the  removal  of  the 
products  of  cell  life  as  it  is  upon  the  supply  of  pabulum.  If  the  area 
involved  be  large,  and  the  process  be  sufficiently  marked,  coagulation 
necrosis,  followed  by  gangrene,  may  occur.  Such  extensive  necrotic 
processes  are,  of  necessity,  preceded  by  stasis.  Congestion  is  likely 
to  persist  postmortem  and  to  be  evident,  thereby  differing  from  hyper- 
emia. The  form  of  congestion  that  develops  after  the  cessation  of 
circulation,  known  as  snggillation,  must  be  differentiated  from  conges- 
tion that  arose  during  life.  Postmortem  suggillation  is  not  usually 
accompanied  by  edema,  and  the  affected  tissues  do  not  show  the  nu- 
tritive changes  that  accompany  antemortem  venous  stasis.  (See  pages 
5  and  6.) 

Stasis, — When,  as  the  result  of  slowing  the  circulation,  the  ob- 
struction of  gravity,  inflammation,  or  of  injury,  the  blood  stops  circu- 
lating in  the  capillaries  of  an  area,  the  condition  is  called  stasis.  It 
is  a  very  common  sequence  of  congestion,  occasionally  occurs  in  hyper- 
emia, and  is  a  more  or  less  constant  phenomenon  in  inflammation. 
The  extent  of  stasis  in  inflammatory  processes  is  dependent  upon  the 
activity  of  the  inflammation  and  upon  the  recuperative  powers  of  the 
circulation.  The  virulence  of  the  infection  is  no  doubt  also  a  deter- 
mining factor.  In  addition  to  the  causes  just  mentioned,  stasis  occa- 
sionally arises  as  a  result  of  tension  occluding  the  blood-vessels  to  or 
from  an  area,  and  may  also  be  caused  by  inspissation ;  as,  for  example, 
from  prolonged  exposure  of  serous  surfaces,  notably  the  peritoneum. 


CIRCULATORY    I)ISTURBANXI>  7l>~ 

The  corpuscular  changes  terminate  in  iHssolution,  iraj^uuMUatK.n  m  the 
cells,  and  not  infrequently  necrosis  of  the  capillary  walls;  the  necrotic 
jjroccss  may  also  involve  the  perivascular  structures. 

Edema'  implies  abnormal  or  excessive  transudation  of  the  fluid 
portion  of  the  Mood  into,  or  its  unusual  retention  in,  the  lymph-sitaccs. 
As  the  large  serous  cavities  are  generally  conceded  to  be  lym[)h-spa(cs. 
the  accumulation  of  serum  such  as  is  seen  in  the  ascites  that  may  accom- 
pany cirrhosis  of  the  liver  belongs  truly  to  the  edematous  condition. 

Causes. — The  pathology  of  edema  is  intimately  associated  with 
the  normal  process  of  lymph  formation.  When  ])hysiologists  satis- 
factorilv  determine  the  origin  of  lymph,  we  shall  be  l»etter  able  to 
appreciate  the  overdistention  of  the  lymph-spaces  seen  in  edema. 
It  is  probable  that  the  cause  of  edema  is  never  a  single  factor,  usually 
depending  upon  a  combination  of  conditions,  among  which  may  be 
considered  alterations  in  the  blood,  in  the  blood-pressure,  and  in  the 
capillarv  wall,  and  interferences  with  the  normal  How  of  lymph.  To 
these  may  possibly  be  added  decreased  perivascular  pressure,  and  pos- 
siblv  chemic  and  structural  changes  in  the  tissues;  that  the  nervous 
svstem  mav  exert  a  certain  causative  influence  can  not  be  overlooked, 
but  the  nature  of  the  factor  or  the  manner  of  its  action  can  not  be  so 
accuratelv  determined.  Some  are  inclined  to  believe  that  abnormalities 
of  the  blood  will  not  produce  edema  until  sufficient  time  has  elapsed  for 
the  blood  alterations  to  give  rise,  either  directly  or  indirectly,  to  changes 
in  the  vessel  walls.  The  changes  in  the  vessel  walls  consist,  for  the 
most  part,  of  alterations  in  the  endothelium  of  the  ca])illaries.  The 
endothelium  may  become  granular,  cloudy,  or  even  partially  exfoliated. 
With  such  alterations  in  the  endothelium  enlargement  of  the  stomata 
occurs,  or  even  separation  of  the  endothelial  plates  along  their  line 
of  juncture.  It  is  probable  that  in  all  forms  of  edema,  arising  from 
increased  blood-pressure,  some  change  in  the  endothelium  is  an  essential 
part  of  the  process.  When  there  is  an  obstruction  to  the  onward  flow 
of  the  blood,  such  as  may  occur  from  ligation  or  occlusion  of  the  pnn- 
cipal  veins,  or  when  there  is  retardation  in  the  progress  of  the  blood, 
which  increases  the  pressure  in  the  capillaries  and  leads  to  such  de- 
generative changes  in  the  endothelium   as  to  permit  extravasation   of 

'  The  literature  of  edema  is  very  extensive.  The  most  impjortant  can  Vk  tr.uotl 
from  the  following  articles:  Chantemesse  and  Podwyssotsky,    •  Ix-s  Pre  it- 

aux,"    1905,  vol.  ii,  p.  331.       Meltzer.    Harrington  Lectures,    Univcrsr  lo. 

1904,  reprint;  also  "American  Medicine,"  July  9,  16,  23,  and  30,  1904.    I  In 

temational  Clinics,"  1904,  vol.  iv.  13th  series.     Harrington,  "Boston  M-  r^ 

Jour.,"  March  30,  1905.  p.  362.   Merklen  and  Heitz,  "  Bull,  dc  la  Soc.  Moi   u.    ■  .ui.s." 
Jan.  21,  1904,  p.  26.     Bodin,  "  Ptiuger's  Arch.."  Sept.  30.   1004.     Apcrt  and  Dc- 
lille,  "Lancet."  Jan.  7,   1905,  p.  4.?-      Baum,  "Berl.  kl"'    W.^n     '    r..n     .•     imoc 
Valobra,  "Soc.  de  Neurol,  de  Paris."  March  2,  1905.     S 
Iconogr.  de  la  Salpetricre,"  May-June,  1904.     Achar.1 

des  M6d.  des  H6p.."  July  2s,  1903.     Courmont.  i; 

^3.      Dopter  and  Tanton^  "  6ull.  et  Mem.  de  la  S< 
jixlv  18,  1901,  No.  25.     Albu,  "Virch.  Arch.,"  1901.  IM 
of  Path,  and  Bact.,"  Aug.,  1903.  P-  67.     Loeper.  "  La  I' 
p.  630.      Widal  and  Javal,  "La  Presse  Med.."  Oct     - 
Ratherv,  "Arch,  de  Med.  Exper.,"  Sei)t..  1903.  p 
"Wien.'klin.  WcKrh..  '  Oct.   13.  1904.     Morris,  "A:. 

1904,  p.  812.     Osier,  "Amer.  Jour,  of  Med.  Sci.,"  Jan..  1904.  P-   »  ^*- 

"Amer.  Jour,  of  Med.  Sci.,"  Sept..  100?.  p.  44.?:    a'sq  May.  1904.  r  "^• 

"Zieg.  Beitr..  '  1904.  Bd.  36.  p,  435 


268  GENERAL  PATHOLOGY. 

the  serum,  edema  results.  Similarly,  venous  congestion,  due  to  inability 
of  the  heart  to  propel  the  venous  blood,  ma}'  induce  a  similar  lesion, 
called  cardiac  edema.  That  edema  produced  by  obstruction  to  the  on- 
ward flow  of  the  blood  is  directly  due  to  the  increased  intracapillary 
pressure  can  not  be  said  definitely  to  be  demonstrated.  It  is  prob- 
able that  it  arises,  in  part  at  least,  as  a  result  of  associated  degen- 
erative changes  in  the  endothelium,  increasing  the  permeability  of 
the  vascular  wall  and  permitting  the  occurrence  of  serous  transuda- 
tion. 

The  fact  that  the  blood-vessels  in  an  edematous  area  may  show 
no  recognizable  structural  lesion  has  led  to  the  belief  that  edema 
may,  under  certain  circumstances,  be  dependent  upon  an  in- 
creased secretory  action  of  these  cells,  presuming,  of  course,  that  the 
normal  Ivmph  is  produced  by  a  process  of  secretion  and  not 
simply  by  transudation.  The  presence  of  certain  materials  in  the 
circulation  undoubtedly  favors  the  occurrence  of  edema.  For  the 
most  part  these  are  toxic  substances,  of  which  bacterial  poisons  may 
be  taken  as  examples.  It  is  not  improbable  that  they  increase  the 
difEusibility  of  the  serum  and  at  the  same  time  injure  the  endothelial 
cells.  The  edemas  that  occur  in  the  last  stages  of  tuberculosis,  and 
in  various  cachexiae  associated  with  lowered  nutrition,  are  probably 
dependent  upon  the  faulty  nourishment  of  the  vascular  endothelium 
as  well  as  upon  alterations  in  the  blood,  and  in  not  a  few  of  these  the 
presence  of  toxic  materials  in  the  circulating  fluids  can  not  be  positively 
excluded  as  adjuvant  factors.  The  influence  of  tissue  tension  in  the 
occurrence  of  edema  must  not  be  overlooked.  With  vascular  changes 
practically  the  same,  edema  must,  of  necessity,  occur  with  more  rapidity 
in  lax  tissues,  such  as  the  eA'elid  and  scrotum,  than  in  tissues  of  greater 
density,  such  as  periosteum  and  bone.  Normally,  the  nutrition  of  the 
tissues  is  maintained,  in  part  at  least,  by  serum  passing  out  from  the 
vessels  into  the  perivascular  structures  (primitive  lymph-spaces) ;  the 
cells  abstract  from  this  fluid  the  elements  necessary  for  their  nutrition, 
and  yield  to  it  excrementitious  products,  after  which  it  is  removed 
from  the  tissues  by  the  lymph-stream.  It  will  be  seen  that  any  obstruc- 
tion to  the  onward  flow  of  the  lymph,  such  as  may  result  from  pressure 
upon  the  lymph-duct,  may  give  rise  to  an  accumulative  edema  in  the 
area  drained  without  the  necessity  of  presupposing  any  degenerative 
change  in  the  blood-vessels  of  the  part. 

As  a  result  of  the  studies  of  Widal,  Achard,  Loeper,  and  other  French 
observers,  great  stress  is  at  present  being  laid  on  the  relation  between 
the  sodium  chlorid  content  of  the  tissues  and  the  occurrence  of  edema. 
If  for  any  reason  an  excess  of  this  salt  be  present  in  the  connective  or 
other  tissues,  the  attempt  to  maintain  isotonicity  results  in  an  excess 
of  fluid  accumulating  in  the  structures  containing  the  abnormal  amount 
of  sodium  chlorid.  It  is  not  certain  that  any  other  salt  exerts  exactly 
the  same  action.  This  theory  of  edema  formation  has  been  turned 
to  therapeutic  advantage;  dropsical  patients  are  given  salt-free  diet 
and  elimination  of  the  sodium  chlorid  facilitated  in  every  way  possible 
The  results  seem  to  add  support  to  the  theory  upon  which  the  treat- 
ment is  based.  Admitting  the  correctness  of  the  French  observers, 
the  necessity  for  explaining  the  excess  of  sodium  chlorid  is  no  less 
urgent  than  the  original  proposition.     The  fact  that  salt  excretion  is 


CIKCUI.ATOKY    DISTURBANCES.  J69 

less  active  iluring  certain  inMainmations  (croupous  ])neuinonia)  and 
intoxications,  indicates  that  the  substance  constitutes  an  important 
part  of  the  protective  influences  of  the  body,  and  is  esj)ccially  necessary 
in  resisting  bacteria,  bacterial  toxins,  and  some  other  poisons.  Tissues 
subjected  to  the  action  of  toxic  bodies  may  extract  salt  fnmi  the  cir- 
culating fluids,  and  this  in  turn  be  followed  by  an  accumulation  of 
serum.  It  has  been  demonstrated  that  in  renal.  an<l  sometimes,  although 
not  invariablv,  in  cardiac  dropsies,  the  sodium  chlorid  content  of  the 
afTected  tissues  is  aV)ove  the  normal. 

However,  the  edema  fluid  enters  the  lymph-spaces  or  lymph- 
vessels,  and  whatever  may  be  the  cause  of  its  accumulation,  there 
is  no  reasonable  doubt  as  to  its  origin;  it  is  derived  from  the  liquor 
sanguinis,  from  which,  however,  it  differs  in  the  lessened  proteid 
content,  the  usual  al)sence  of  all  the  factors  necessary  to  form  fibrin,  its 
lower  specific  gravitv,  and  minor  differences  in  the  proportion  of  salts. 

The  studies  of  Merklen  and  Heitz,  and  also  Kostkevitch,  have 
shown  conclusivelv  that  most  edema  fluids  contain  toxic  sulistances, 
and  that,  when  rapidly  absorbed,  may  give  rise  to  nervous,  cardiac, 
and  renal  disturbances.  The  character  of  these  poisons  no  doubt 
differs  and  is  largely  determined  by  the  cause  of  the  edema.  When 
removed,  the  absorption  of  edema  fluids  is  accomplished  by  the  blood- 
vessels, principally  the  veins,  and  by  the  lymphatics. 

A  form  of  edema  known  as  edema  ex  vacuo  is  said  to  occur  when 
brain-tissue  or  tissue  from  the  spinal  cord  disappears  by  any  process, 
and  the  resulting  cavity,  or  loss  of  structure,  or  shrinking  of  the 
organ,  must  be  tilled  in. 

Edema  is  often  named  for  the  cause  that  gives  rise  to  the  lesion  in 
the  blood-vessel  or  blood  primarily.  Such  edema  may  be  known  as 
toxic,  infections,  cachectic,  traumatic,  ischeunc,  injlamwatory,  thermal. 
or,  in  some  cases  (as  when  the  dilatation  of  the  blood-vessels  is  de- 
pendent upon  errors  or  lesions  in  innervation),  the  condition  may  be 
spoken  of  as  trophic  edema  or  tieiiropathic  edema. 

Morbid  Anatomy. — Edematous  tissue  is  usually  pale,  pits  on  pres- 
sure, and  as  a  result  of  the  deficient  circulation  of  the  blood,  is  lower 
in  temperature  than  the  normal.  On  incision  serum  escapes,  and  the 
waterv  condition  of  the  tissue  can  be  readily  seen.  By  reason  of  the 
deficient  circulation,  the  resistance  of  such  tissue  is  lowered,  and  this 
renders  it  extremely  susceptible  to  infectious  and  necrotic  processes. 
Not  uncommonlv  the  edematous  tissue  shows  well-marked  and  advanced 
degenerative  changes.  (See  Hydropic  Degeneration,  p.  245.)  Edema 
fluids,  spoken  of  as  transudates,  differ  in  some  respects  from  inflamma- 
torv  accumulations,  called  exudates.  The  former  possess  a  low  specific 
gravity  are  poor  in  cells,  and  contain  a  relatively  small  proportion  of 
albumin.  A  specific  gravity  of  1016  to  1020  is  not  uncommon  in  inflam- 
mator>'  exudates,  while  dropsical  collections  rarely  attain  a  specific 
gravity  of  1015,  usually  falling  below — loog  to  loio.  Transudates 
are  commonly  clear  and  poor  in  cells,  of  which  the  mononii  o- 

cytes  and  endothelium    are   most    numerous;  exudates  are  nd 

usuallv  rich  in  leukocvtes. 

The  histologic  studies  of  Kurt  show  that  m  edematon.  fiss-i.s  the 
fibrous  and  elastic  elements  are  swollen,  hyaline,  and  ot'  d. 

Lvmph-spaces  are  more  or  less  dilated,  and  usually  coi.;...  •''- 


270  GENERAL  PATHOLOGY. 

mal  number  of  leukocytes,  especially  of  the  mononuclear  type.  The 
affected  epithelial  cells  imbibe  an  excess  of  fluid  and  frequently  show 
the  so-called  hydropic  spots  or  vacuolated  areas ;  fragmentation  and 
deficient  tingibility  are  practically  always  present  in  the  chromatin 
of  cells  in  edematous  areas.  The  cells  of  the  central  nervous  system 
in  edema  affecting  the  brain,  cord,  or  meninges  are  similarly  altered. 
Different  names  have  been  given  to  the  accumulations  of  dropsical 
fluids,  based  upon  the  location,  cause,  or  admixture  with  other  fluids. 
When  the  edema  is  more  or  less  general,  the  term  hydrops  universalis 
is  applied ;  edema  of  the  connective  tissues,  particularly  of  subcutaneous 
connective  tissues,  is  called  anasarca;  dropsy  of  the  peritoneum  is 
spoken  of  as  hydro  peritoneum  or  ascites;  dropsy  of  the  pleura  as  hydro- 
thorax,  which  condition  may  be  unilateral  or  bilateral;  dropsy  of  the 
pericardium,  as  hydropericardium;  fluid  accumulation  in  joints,  as 
dropsy  of  the  joints  or  hydrops  articuli.  Fluid  accumulation  in  the  cere- 
bral ventricles  is  called  internal  hydrocephalus,  and  when  the  excess  is 
in  the  meninges  or  brain  substance,  cerebral  edema;  the  latter  is 
also  known  as  external  hydrocephalus.  The  origin  of  edematous 
collections  is  sometimes  indicated  by  the  name:  as,  for  example,  renal 
dropsy,  cardiac  dropsy,  congestive  dropsy,  angiosclerotic  edema  (edema 
associated  with  sclerotic  changes  in  the  blood-vessels).  Reference  has 
already  been  made  to  the  toxic,  infectious,  and  other  forms  of  edema. 

THROMBOSIS. 

A  thrombus^  is  a  more  or  less  uniformly  solid  or  semisolid  body, 
formed  during  life  in  the  heart  or  blood-vessels  and  resulting  from 
causes  that  lead  to  the  agmination,  agglutination  or  coagulation  of 
one  or  more  elements  present  in  the  blood.  The  older  definition — 
an  antemortem  intravascular  clot — did  not  take  into  consideration 
the  agmination  and  agglutination  of  platelets  and  leukocytes.  Most 
thrombi,  however,  are  nothing  more  than  fibrinous  coagula,  relatively 
rich  in  leukocytes  and  platelets.  The  term  thrombosis  is  applied  to 
the  process  terminating  in  the  formation  of  a  thrombus.  It  is  also 
somewhat  loosely  used  to  cover  the  associated  conditions. 

In  most  instances  there  is  little  difficulty  in  differentiating  thrombi 
from  postmortem  clots.  Coagula  formed  after  death  have  certain 
points  that  are  highly  characteristic;  they  are  usually  smooth  on  the 
surface,  and  show  no  attachment  to  the  vessels  in  which  they  lie, 
although  they  may  be  entangled:  as,  for  example,  in  the  muscular  col- 
umns or  the  tendinous  cords  in  the  heart.     This  absence  of  attach- 

'Eichhorst,  "  Dent.  Arch.  f.  klin.  Med.,"  Bd.  Ixxx,  p.  75.  Steiner,  "Bull. 
Johns  Hopkins  Hospital,"  June,  1902,  p.  130.  Flexner,  "Univ.  of  Penna.  Med. 
Bull.,"  Nov.,  1902.  Pearce-Gould,  Lettsonian  Lectures,  "Lancet,"  June  7,  1902. 
Clark,  "Univ.  of  Penna.  Med.  Bull.,"  July,  1902.  Orlowski,  "  Russki  Vratch," 
vol.  ii,  No.  6.  Moore,  "Lancet,"  Dec.  19,  1903,  p.  1715.  Loeb,  "Montreal  Med. 
Jour.,"  July,  1903.  Gerster,  "Trans.  Amer.  Surg.  Assoc,"  1903.  Mignon  and 
Dopter,  "La  Presse  Med.,"  Oct.  29,  1904,  p.  689.  Pearce  and  Winne,  "Amer. 
Jour,  of  Med.  Sci.,"  Oct.,  1904.  Weinberger,  "Wien.  klin.  Woch.,"  Jan.  21,  1904, 
p.  64.  Aldrich,  "N.  Y.  Med.  Jour.,"  March  5,1904,  p.  442.  Osswald,  "  Deut. 
Zeit.  f.  klin.  Med.,"  vol.  53.  Goldsborough,  "Johns  Hopkins  Hosp.  Bull.,"  June, 
1904,  p.  193.  Thayer,  "Med.  News,"  Oct.  i,  1904,  p.  637.  Le  Tohic,  These  de 
Paris,  1904.  Chantemesse  and  Podwyssotsky,  "  Les  Processus  Generaux,"  1905, 
vol.  ii,  p.  134,  bibliography. 


ClkCl'LAToKY    DISTL'RHANCES.  27  I 

meiil  is  liiglily  iiiii)()rlant ;  even  when  a  tliromljus  has  been  dislodged 
from  its  place  of  origin,  the  point  from  whit  h  the  thrombus  has  been 
detached  can  usually  be  easily  recognized  as  a  roughenetl  area  upon 
the  blood-vessel  or  heart  wall,  cardiac  orifice,  or  valve  leaflet.  In 
manv  instances  an  area  on  the  thrombus  that  shows  evidence  of  past 
attachment  can  be  found.  The  postmortem  clot  possesses  a  moist,  glis- 
tening surface,  is  usually  red  in  color;  some  ])art  of  it  always  shows 
the  redness  due  to  red  blood-cells,  and  an  important  differentiation, 
for  which  we  are  indebted  to  Cohnhcim,  is  that  in  the  thrombus  there 
is  little  difticulty  in  accomplishing  longitudinal  splitting.  The  throm- 
bus usually  has  a  frayed-out  end.  A  postmortem  clot  does  not  show  the 
changes  that  may  be  seen  proceeding  in  a  thrombus.  (See  p.  275.) 
Occasionallv.  where  postmortem  coagulation  of  the  blood  goes  on  very 
slowly,  sufficient  time  elapses  for  the  red  blood-cells  to  settle  to  the  most 
dependent  portion,  giving  rise  to  a  clot  the  upper  layers  of  which 
are  colorless  and  jelly-like,  while  the  lower  stratum  shows  a  deeper 
color  than  usual  bv  reason  of  its  richness  in  red  blood-cells. 

Very  often,  when  life  is  almost  extinct  (agonal  period),  the  very 
slow  rate  at  which  the  blood  is  flowing  may  favor  the  occurrence  of 
thrombi,  which,  later,  become  continuous  with  postmortem  clots,  coagu- 
lation going  on  around  the  thrombus  after  death.  While  not  restricted 
to  the  right  side  of  the  heart  and  the  pulmonary  artery,  such  clots 
frequently  cocur  in  that  location. 

Red  thrombi  contain  blood  coloring-matter  usually  in  the  entangled 
red  blood-cells;  these  are  the  thrombi  that  form  in  stagnant  or  prac- 
tically quiescent  blood.  White  thrombi  are  thrombi  consisting  of  fibrin 
with  a  varying  number  of  leukocytes  and  blood-platelets,  and  are 
formed  in  flowing  blood.  Thrombi  may  be  mixed — the  so-called  gray 
thrombi,  in  which  the  gradual  slowing  of  the  blood  has  led  to  a  slight 
deposit  of  red  blood-cells  with  the  forming  and  condensing  fibrin.  As 
a  result  of  ribbed,  "frayed-out,"  or  irregular  thrombus-formation, 
longitudinal  cavities  are  sometimes  produced  in  which  the  more  or 
less  quiescent  blood  proceeds  to  clotting,  and  thereby  becomes  a  part 
of  the  completed  thrombus.  This  condition  gives  rise  to  thrombi  that 
may  be.  in  a  sense,  mixed,  certain  parts  being  distinctly  red.  other 
parts  gray,  and  still  other  areas  red  and  jelly-like,  closely  resembling 
the  thrombi  formed  elsewhere  in  quiescent  blood.  When  the  mass  is  com 
posed  of  layers,  such  as  occur  in  the  cavity  of  an  aneurysm,  the  thrombus 
is  said  to  be  stratified.  When  a  thrombus  remains  where  it  originated 
and  arises  independent  of  other  thrombi,  it  is  called  a  primary  thrombus. 
The  term  propagated  thrombus  is  api)lied  to  a  thrombus  that  extends 
some  distance  from  the  point  at  which  it  originate<i;  such  thrombi 
are  extremely  likely  to  show  different  ages  at  different  points,  and 
may  extend  to  an  indefinite  length.  A  thrombus  developing  from  an 
embolus,  or  a  thrombus  that  arises  secondary  to  an  existing  thrombus. 
is  known  as  a  secondary  thrombus.  When  a  thrombus  leads  to  occlusion 
of  the  blood-ycssel  or  cardiac  orifice  in  which  it  lies,  it  is  said  to  be 
an  obstructing  thrombus.  When  it  permits  the  blood  to  flow  one  wav 
and  occludes  a  current  flowing  in  the  opposite  direction,  it  is  termed 
a  valve  thrombus.  When  the  thrombus  lines  the  wall  of  a  cavity.— 
c.  (^..  an  aneurysm  or  a  blood-vessel,— it  is  known  as  a  parietal  or  a 
mural   thrombus.     When  a  thromb-i-   .«vton,U  .-.r.. md    a   blood-vessel. 


272  GENERAL  PATHOLOGY. 

it  is  said  to  be  annular  ;  if  formed  with  a  distinct  canal,  it  is  spoken 
of  as  a  channeled  or  canalized  thrombus.  The  "ball  thrombus''  is  not 
attached,  although  evidence  of  recent  attachment  may  be  present 
either  on  the  thrombus  or  on  the  vascular  or  cardiac  wall;  a  point 
of  separation  from  a  fragment,  still  attached,  may  often  be  recognized. 
Ball  thrombi  are  most  frequently  found  in  the  dilated  left  auricle  in 
cases  of  mitral  stenosis.  Polypoid  or  pedunculated  thrombi,  so-called 
cardiac  polypi,  are  most  frequently  seen  in  the  left  auricle;  the  point 
of  attachment  is  usually  the  margin  of  the  fossa  ovalis  or  its  immediate 
vicinity.  The  pedicle,  and  not  uncommonly  a  larger  part  of  the  throm- 
bus, may  show  advanced  organization.  The  structure  of  such  partly 
organized  polypi  may  resemble  fibrous  or  myxomatous  tissue,  and 
hence  they  have  been  termed  fibromatous  and  inyxoinatous  polypi  re- 
spectively. An  endothelial  covering  is  sometimes  demonstrable,  and 
calcareous  infiltration  may  be  in  an  early  stage  or  even  advanced. 

The  most  important  division  of  thrombi  is  into  simple  or  bland,  and 
infected  or  infective,  the  former  including  the  aseptic  thrombi,  containing 
no  bacteria,  the  latter  terms  being  applied  to  thrombi  in  which  bacteria 
are  present,  hence  infected  thrombi.  A  further  division  of  infected  thrombi 
has  been  proposed.  It  is  suggested  that  the  term  septic  thrombi  be 
applied  to  those  in  which  organisms  of  suppuration  are  present,  and 
the  term  putrid  thrombi  to  those  that  contain  bacteria  of  decomposition. 
The  fact  that  the  bacteria  of  decomposition  may  be  present  alone  or 
associated  with  the  organisms  of  suppuration  deprives  such  a  division 
of  much  of  its  theoretic  value. 

Thrombi  are  sometim3s  called  arterial  or  venous,  and,  under  the 
latter,  a  separate  form  is  named,  dependent  upon  its  location  in  a 
distinct  venous  system— portal  thrombi. 

Causes. — The  essential  exciting  cause  of  a  thrombus  is  that  process 
terminating  in  coagulation  of  the  blood.  Other  causes  are:  (i)  Any 
body  within  the  circulation,  not  covered  by  endothelium,  leading  to 
attachment  of  blood-platelets  and  to  the  subsequent  formation  of 
a  clot  or  thrombus;  (2)  roughening  of  the  vascular  wall,  as  observed 
in  atheroma;  (3)  slowing  of  the  circulation,  such  as  occurs  in  partial 
occlusion  of  a  blood-vessel,  or  in  complete  obstrtiction,  as  represented 
by  ligation.  It  is  maintained,  and  probably  justly,  that  a  blood- 
vessel may  be  ligated  and  its  lumen  occluded  without  the  intervention 
oi  a  clot.  This  implies  great  care  in  apphang  a  ligature,  so  that  it 
does  not  injure  the  endothelium.  When  a  blood-vessel  is  ligated  in 
its  continuity,  two  thrombi  are  usually  formed:  one  on  the  cardiac 
side,  known  as  the  proximal  thrombus,  and  a  second  in  the  blood-vessel, 
beyond  the  point  of  ligation,  known  as  the  distal  thrombus.  It  is 
probable  that  complete  or  partial  obstruction  gives  rise  to  changes  in 
the  endothelium  of  the  vessel  wall,  and  this  favors  the  mural  lodgment 
of  leukocytes  and  third  corpuscles,  and  hence  of  a  thrombus.  As  will 
be  noted  later,  the  formation  of  a  thrombus  is  not  essential  to  the 
obliteration  of  a  blood-vessel  in  which  the  circulation  has  ceased.  In- 
deed, it  is  held  by  some  authors  that  thrombosis  interferes  with  the 
obliterative  endarteritis  that  normally  leads  to  the  disappearance  of  a 
blood-vessel.  (4)  An}^  alteration  in  the  vessel  wall  that  injures  the  endo- 
thelium favors  the  development  of  a  thrombus.  (5)  Chemic  changes 
in   the    blood    also    facilitate    the   occurrence   of    thrombosis;    throml)i 


CIRCULATORY  DISTURBAN'CES.  273 

partly  due  to  this  cause  are  seen  in  dijihtlieha  and  in  adynamic  con- 
ditions with  very  nnuh  slowcil  and  enfeebled  circulation.  Such  thrombi 
are  called  marasmic  thrombi.  (6)  Hyjierinosis,  such  as  develops  in 
pregnancy,  is  natures  niethod  of  anticipating  hemorrhage,  the  m- 
creased  amount  of  fibrin  favoring  the  arrest  of  bleeding  by  the  develop- 
ment of  thrombi.  Hyperinosis  is  not  of  itself  an  exciting  cause  of 
thrombosis,  as  many  conditions  are  associated  with  an  increase  in  the 
amount  of  fibrin-forming  elements  in  the  blood  without  any  marked 
tendency  toward  the  occurrence  of  thrombosis.  ( 7 )  Chemic  changes 
leading  to  a  thrombus  may  be  produced  in  the  blood  by  the  injection 
of  certain  agents:  c.  g.,  ether.  (8)  Where  a  tumor  infiltrates,  comes 
in  contact  with,  or  penetrates  a  blood- vessel,  a  thrombus  fretjuently 
forms.  (9)  A  primary  thrombus  favors  the  development  of  secondan.' 
thrombi.  (10)  Mycoses  of  the  blood  may  give  rise  to  or  follow  throm- 
bosis,    (ii)    Embolism  often  leads  to  thrombus-formation. 

The  old  discussion  as  to  whether  thrombosis  dejjended  upon  changes 
in  the  blood,  or  alterations  in  the  vessel  wall,  apf)ears  to  have  been  satis- 
factorily settled.  Bacteria  or  bacterial  products  in  the  circulating 
blood  acting  upon  the  vessel  wall  alter  the  endothelium,  favor  the 
deposit  of  platelets  or  leukocytes,  thereby  forming  a  nucleus  upon 
which  thrombus  formation  progresses.  The  studies  of  Eichhorst, 
Steiner,  Thayer,  and  others  have  clearly  estah)lished  the  influence  of 
infectious'  diseases  on  the  production  of  thrombosis.  Eichhorst  was 
able  to  collect  42  instances  of  thrombus  formation  in  typhus,  40  in 
typhoid,  and  19  in  influenza.  He  believes  that  the  thrombus  formation, 
in  certain  instances  at  least,  is  due  to  bacterial  invasion  by  way  of 
the  vasa  vasorum.  Steiner  found  41  instances  of  thrombosis  com- 
plicating pneumonia;  Orlowski  was  able  to  collate  38  cases  in  which 
thrombosis  of  the  abdominal  aorta  complicated  infectious  disease. 
Thaver  analvzed  42  cases  of  venous  thrombosis  occurring  in  the  course  of 
tvphoid  fever.  Thromboses  of  the  uterine  sinuses  and  of  the  pelvic  and 
saphenous  veins  are  not  infrecjuently  results  of  septic  processes  in  the 
uterus,  parametrium,  or  pelvic  tissues.  Flexner's  studies  on  the  intra 
vitani  agglutination  of  red  blood-cells  throw  considerable  light  on  the  for- 
mation of  thrombi  in  hemolytic  processes,  and  it  may  be  possible  that 
the  thrombosis  of  chlorosis  has  a  similar  origin.  The  so-called  marantic 
thrombi,  long  held  as  occurring  independently  of  infection,  are  probably 
bacterial  in  origin.  Harris  and  Longcope  found  demonstrable  bacteria 
in  34  of  44  studied.  The  observations  of  Clark  strongly  incline  toward 
the  belief  that  trauma  may  produce  thrombosis  without  the  presence 
of  bacteria,  or  at  least  in  the  absence  of  discernible  infection.  The  ex- 
tension of  inflammaton-  or  septic  processes  from  the  perivascular 
tissue  is  easilv  recognized  as  an  important  cause  of  throml)osis.  Veins 
are  frequentl'v  thrombosed  as  a  result  of  infection  involving  the  area 
in  which  their  branches  are  distributed.  In  inflammations  and  infec- 
tions of  the  appendix,  thrombi  may  be  propagated  along  the  course 
of  the  portal  vessels,  constituting  one  of  the  important  causes  of  hepatu 
abscess  due  to  embolism  from  the  portal  vein.  In  a  like  manner  the 
cranial  sinuses  may  be  infected  from  sept: 
bone,  particularly  the  middle  ear  and  : 
attention  to  the  frequency  with  which  throinl 
to  relapse,  and  cites  a  case  in  which,  during/ 
11; 


274 


GENERAL  PATHOLOGY. 


was  invalided,  at  different  periods,   for  six  years  and  two  months  on 
account  of  thrombosis,  the  origin  of  which  was  obscure. 

Thrombus  formation  begins  as  a  thromboarteritis,  thrombophlebitis, 
or  thrombosinusitis  with  alteration  of  the  lining  endothelium  of  the 
aft'ected  vessel,  the  deposit  of  platelets,  and  possibly  leukocytes,  fol- 


FiG.  146. — Termination  of  Aorta,  the  Common  Iliac,  External  and  Internal  Illacs,  Case  of  Thrombo- 
arteritis DUE  to  Para-uterine  Inflammation  and  Extension  to  the  Vessels  from  Adjacent 
Tissues. 

A .  Thrombus  in  common  iliac  artery  secondary  to  and  an  extension  from  the  primary  thrombus  in  the  right  internal 
iliac.  B.  Point  of  initial  thrombo-arteritis  with  partial  organization  of  a  peripheral  gray  thrombus;  the  central 
more  recent  thrombus  was  red.  Note  the  great  tliickening  of  the  artery  and  periarterial  tissues.  C.  Left  com- 
mon iliac  the  seat  of  acute  endarteritis,  upon  which  a  thrombus  is  just  beginning  to  form. 


lowed  by  superimposed  fibrin.  The  area  of  attachment  in  the  involved 
blood-channel  depends  upon  the  extent  of  the  endothelial  erosion. 
From  its  point  of  origin  a  thrombus  may  be  propagated  in  either  di- 
rection, but  usually  the  extension  is  farthest  in  the  line  of  the  blood- 
current. 


CIRCULATORY   DISTURBANCES. 


275 


Changes  'I' hat  a  Thrombus  May  Undergo. — The  character  of  the 
transformations  observed  in  thrombi  arc  <ic]i(!i'!cnt  upon  whethi-r  the 
process  is  si))iplc  or  iujcctivc.  In  infective  thrombi  the  only  changes 
that  are  likely  to  occur  are  those  constantly  associated  with  infci  lion: 
namely,  liqncjaction,  softening,  or  fragmentation  and  other  alterations 
that  commonly  accompany  necrosis;  rarely,  in  infected  thrombi,  dis- 
lodgment  may  occur.  With  the  cxcej^tion  of  softening  the  changes 
to  be  considered  in  simple 
thrombi  seldom  take  place  in 
infected  thrombi.  The  frag- 
ments of  an  infected  throm- 
bus become  infected  emboli, 
and  lead  to  dissemination  of 
the  infective  material  and  to 
its  deposit  in  other  parts  of 
the  body;  besides  this,  in- 
fected thrombi  are  constantly 
throwing  into  the  circulation 
bacteria,  or  the  products  of 
bacterial  life,  this  condition 
constituting  what  is  known 
as  septicemia,  bacteremia,  or 
mycosis  of  the  blood.  When 
the  infected  material  con- 
tains pyogenic  organisms,  the 
emboli,  lodging,  give  rise  to 
abscesses;  such  abscesses  are 
spoken  of  as  pyemic  or 
)netastatic,  and  the  disease 
is  known  as  pyemia.  Before 
the  elucidation  of  the  subject 
of  blood-poisoning,  afforded 
by  our  knowledge  of  bacteria 
and  infectious  processes,  it 
was  presumed  that  metastatic 
abscesses  resulted  from  the 
presence  of  pus  in  the  blood; 
hence  the  name  pyemia.  It 
is  now  known  that  the  con- 
dition is  due  not  of  necessity 
to  the  presence  of  formed 
pus,  but  to  agents  capable  of 
inducing  suppurative  pro- 
cesses— bacteria. 

The     following     changes 
may  occur  in  thrombi: 

/.  Dislodgmcnt  occurs  but  rarelv.  The  cases  that  the  writer  has 
observed  have  been  from  large  tumors  of  the  uterus,  where  a  throm- 
bus had  formed  in  one  of  the  massive  sinuses  of  such  a  tumor,  and. 
becoming  dislodged,  had  reached  the  lung  and  blocked  the  larger  ves- 
sels to  that  organ,  leading  to  almost  instant  death.  Dislodgment  of 
a  thrombus  is  favored  bv  anv  sudden  increase  in  the  rapidity  of  the 


':\i^r:i^^^^6^'/}i'^£iz'^.'-^'^ 


;.  147.— Section  TiiHi-iiii  a  V\^ 
Contained  Ubgani/inc.  Tiir'  ■ 


It* 


fully  .1. 
l.-iltcr  1 


tiiuMC  cttcAtiuig  tnlu  tiic  ihruiuliiu,  ihc 


276 


GENERAL  PATHOLOGY. 


—     .     >->^ 


f 


circulation,  particularly  when  the  accelerated  current  is  brought  di- 
rectly in  contact  with  the  thrombus;  manipulation  of  the  diseased 
part,  or  even  comparatively  slight  muscular  movement  in  an  affected 
limb,  when  an  extremity  is  involved,  may  detach  a  loosely  adherent 
thrombus.  A  ball  thrombus,  in  the  left  auricle,  may  become  jammed 
into  the  mitral  orifice. 

2.  Decolorizaiion  is  possible  only  in  the  red  thrombus,  and  is  due 
to  the  gradual  absorption  of  the  coloring-matter  by  the  circulating 
blood,  which  flows  over,  around,  or  through  it,  and  to  the  removal  of 
precipitated  coloring-matter  by  phagocytic  cells. 

J.  It  is  difficult,  if  not  quite  impossible,  to  demonstrate  the  occur- 
rence of  rc-soltition;  but  there  can  be  no  doubt  that  the  simple,  non- 
infected  thrombus,  due  to  temporary  conditions,  may  be  dissolved  or 

may    undergo    solution    upon 
the  removal  of  the  cause. 

4.  Softening  is  not  so  com- 
mon in  the  simple  as  in  the  in- 
fected thrombus,  and  is  usuall}^ 
due  to  conditions  of  develop- 
ment, to  the  location  and  size 
of  the  thrombus,  and  to  blood 
changes  and  infection  that 
militate  against  the  process  of 
organization.  When  this 
change  occurs  without  infec- 
tion, it  is  termed  simple  soften- 
ing; when  bacteria  are  present, 
septic  or  infective  softening. 
When  softening  and  disinte- 
gration occur,  the  fragments, 
reaching  the  circulation,  form 
simple  or  infective  emboli,  de- 
pending on  whether  the  throm- 
bus contained  viable 'organisms 
or  not;  more  commonly,  in- 
stead of  softening,  there  is 
really  a  condition  of  fragmen- 
tation, in  which  nothing  more  than  the  end  of  a  thrombus  is  broken  off. 
5.  Organization  is  possible  only  in  the  absence  of  infection.  It 
may  occur  in  infected  thrombi  after  the  subsidence  of  infection,  al- 
though upon  this  point  there  must  remain  much  doubt.  The  con- 
version of  the  thrombus  into  connective  tissue  is  effected  largely  through 
the  activity  of  the  endothelial  cells  of  the  intima.  Before  the  begin- 
ning of  organization  considerable  contraction  is  usually  brought  about 
by  removal  of  the  fluids  present  in  the  thrombus,  and  possibly  by  a 
certain  amount  of  liquefaction  and  absorption.  Where  the  thrombus 
becomes  continuous  with  the  intima,  the  endothelium  gradually  ex- 
tends over  its  surface.  From  this  endothelial  covering,  processes  of 
young  connective-tissue  cells  extend  downward  into  the  thrombus, 
forming  capillaries.  A  similar  proliferation  of  any  viable  endothelium 
beneath  the  thrombus  also  takes  place,  and  young  blood-vessels  from 
the  adjacent  nutrient  branches  are  pushed  forward  into  the  prolifer- 


^^f- 


■  ..   --'^^^ 


Fig.  148. — Transverse  Section  of  a  Thrombosed 
Blood-vessel  in  Which  Organization  and  Can- 
alization OF  THE  Thrombus  Are  in  Progress. 

a.  Newly  formed  connective  tissue  of  the  thrombus,  h. 
Tunica  media,  c.  Tunica  intima.  d.  Young  cell  in- 
filtrate of  the  thrombus.  \  similar  infiltrate  of  the  coats 
of  the  vessel  is  shown  at  /,  /.  e.  e.  Remainder  of  the  not 
yet  organized  thrombus,     h.  Developing  canals. 


CIRCULATORY    DISTURH.WC  KS.  .' ;  ; 

ate.  During  the  extension  of  this  embryonic  tissue  torination  uirther 
absorption  and  shrinkage  of  the  thrombus  oct-ur.  Gradually  the  new 
connective  tissue  replaces  the  thrombus  and  f)rganization  of  the  cica- 
tricial tissue  is  completed  as  usual.  (See  Process  of  Rei)air.)  The 
activity  of  the  leukocytes  in  this  process  is  no  longer  conceded  to  ]->c 
important.  With  the  presence  of  infection  large  numbers  of  leuko- 
cvtes  may  be  found.  They  are  not,  however,  regarded  as  essential 
elements  in  the  production  of  the  formative  tissue  through  which 
organization  is  eventually  completed.  The  influence  of  the  organized 
body  upon  the  blood-vessel  will  be,  of  course,  depentlent  uj)on  the 
extent  and  location  of  the  thrombus  and  upon  the  completeness  with 
which  it  occludes  the  vascular  lumen.  The  effect  of  the  subse- 
tpient  cicatricial  contraction  is  shown  In'  the  deformity  that  it  induces, 
and  is  particularly  marked  in  the  organized  thrombi  that  constitute 
the  vegetations  on  the  valve  leaflets  in  endocarflitis.  (See  Results  of 
Endocarditis.) 

Ck  When  a  thrombus  forms  in  a  slowed  circulation, — -c.  g.,  of  a 
dilated  vein, — and  is  attached  to  the  vessel  or  lodged  in  the  sinus  of 
a  valve,  infiltration  by  lime  salts — calcification — not  uncommonly 
occurs,  producing  the  so-called  phlcboliths,  or  "  vein  stones" ;  arterioliths 
and  stone-like  concretions  attached  to  the  cardiac  walls  or  orifices  are 
produced  in  a  similar  manner;  infiltration  of  lime  salts  is  also  likely 
to  occur  in  a  thrombus  that  is  organizing  or  that  has  organized. 

Modifications  of  some  of  the  foregoing  conditions  are  occasionally 
considered  as  separate  processes;  thus,  a  large  throml)US  may  exhibit 
a  central  softening,  and  postmortem  or  during  an  operation — e.  g.,  on 
aneurvsm — a  thrombus  may  be  found  in  which  liquefaction  necrosis 
has  occurred,  converting  the  center  of  the  mass  into  a  reddish  or 
vellowish  fluid;  this  was  at  one  time  spoken  of  as  cystic  degeneration 
of  a  thrombus;  probably  it  is  an  autolytic  process.  An  attached 
thrombus  mav  remain  more  or  less  quiescent  for  a  considerable  length 
of  time,  or  the  changes  that  it  undergoes  may  be  so  poorly  marked  as 
to  be  scarcely  recognizable. 

Results  of  Thrombosis. — These  are  largely  dependent  upon  the 
character,  location,  and  cause  of  the  thromlms  and  upon  the  changes 
that  the  thrombus  itself  has  undergone;  the  results  due  to  such  changes 
will  suggest  themselves:  e.  g.,  an  organizing  or  obstructing  thrombu^ 
may  more  or  less  fully  occlude  the  blood-vessel;  the  evidence  of  such 
occlusion  depends  upon  whether  the  lilood-vessel  is  the  main  trunk 
to  a  limb  or  one  of  the  less  important  branches;  again,  if  the  thrombus 
form  slowly,  the  collateral  circulation  may  sustain  the  nutrition  of  the 
part.  The  alterations  produced  in  the  blood-vessel  are  depcntlent  upon 
the  changes  that  the  thrombus  undergoes;  these  also  suggest  them- 
selves or  have  been  indicated. 

Thrombosis  may  affect  lacteal,  chylous,  and  lymph-vessels,  produc- 
ing alterations  that  are  not  unlike  the  changes  seen  in  blood -channels. 
The  lessened  force  of  the  current  renders  lymphogenous  embolism  infre- 
quent and  obliteration  of  the  vessel  common.  The  process,  although 
rare,  is  sometimes  seen  in  the  thoracic  duct,  and  may  be  due  to  exten- 
sion of  thrombosis  from  the  subclavian  or  jugular  vein.  Tul)erculosis 
or  other  infective  disease  in  the  tissues  around  the  thoracic  duct  may 
extend  through  the  wall  and  be  propagated  from  the  interior. 


278  GENERAL  PATHOLOGY. 

EMBOLISM.  1 

An  embolus  is  any  body  transported  by  the  circulating  blood,  and 
capable,  by  reason  of  its  physical  characters,  of  obstructing  the 
flow  of  blood  in  any  part  of  the  vascular  system.  As  Park  states,  the 
essential  element  is  transportation  or  carriage  of  some  solid  or  semi- 
solid body  in  the  circulation.  Oil  and  air,  while  not  solid  bodies,  may 
be  impacted  within  the  capillaries,  and  hence  may  constitute  emboli. 
The  transportation  and  lodgment  of  emboli  and  in  part,  at  least,  the  re- 
sulting changes  constitute  the  process  of  embolism.  EmboH  are  usually 
too  large  to  pass  the  capillaries.  They  may  be  composed  of:  (i') 
Thrombi  detached  or  in  fragments.  (2)  Fragments  of  the  cardiac 
valves  or  endocardial  vegetations;  the  latter  truly  thrombi.  (3)  Calca- 
reous plaques.  (4)  Fragments  of  morbid  growths  torn  from  tumor 
masses  that  have  penetrated  a  vessel  wall.  (5)  Purely  extraneous 
bodies,  such  as  bubbles  of  air,  pieces  of  bone,  or  oil  globules  that  may 

have  gained  ingress  as  a  re- 
sult of  fracture  or  injury  to 
/  C^^-iL  -  ,  ^  bone ;  extensive  laceration  of 

_^^J  '■^^f)^^f^^^  ^'^"t^  adipose  tissue  may  also  give 

^V-x     '  '' /^  • '"  °  "^i^is^j/^'t^^n  rise  to  oil  embolism.    Accord- 


'V    -  '-     <'.- 


^-^-j^^r^^n  nsetoouemoonsm.    ac( 

^^'  '^^''  ing    to    Connell,    there 


/ 


^  ^.  — o     -     -- ■-,    -"^^^     are 

'■■/^/A    ,-"■'';,    ^  "i'  ^        about    250  cases   of  fat   em- 

:    "/•>:  ""o'.  ^    '''       /yf/j  bolism    on    record.      It    has 

'/^     ''             ^    ^  X''  followed  subcutaneous  injec- 

\ \'^'  -^^  ■^  .^-''*'  -,  tion  of  oil  and  paraffin.    The 

.-    "^ '£.''-  ■' f  ■/' '.'J^'^  most  common  cause  is  frac- 

-/^'7CS5^i^^4^V'^2>^^  ture  of  bone.    Engel  has  seen 

^6^J       '-'^'firj^  "^  f  fat  embolism  of  the  lung  fol- 

Fio.up.-BRANCH   or   Pui-monahvAkxekv' Containing  ^°^,     hepatlC       injury.  The 

Sarcoma  Cells  from  a  Case  of  Wide-spread  Dis-  Writer     had     an     Opportunity 

orTis'soEOFTjE^TrnGH"""^''"  ^^  SuBcuTANE-        ^^  oh^^xY^  a  death  from  fat 

A.     Sarcoma     ceUs.      B.      Polymorphonuclear     leukocyte.  embolism     following    eXcision 

There  is  some  irregularity  in  the  size  and  shape  of  the  ^f  ^1,„  -rnammfl  fnr  parrinnmfi  • 

red  cells  due  to  the  associated  secondary  anemia.  *-'■'■  ^'■^^  Iliaiiniia  lOr  Carcinoma  , 

the  patient  was  an  unusually 
obese  woman,  fifty  years  of 
age.  As  a  result  of  trauma,  not  only  fat  but  fragments  of  tissue  may  enter 
the  circulation ;  laceration  of  hepatic  tissues  may  result  in  the  displace- 
ment of  fragments  that,  later,  may  be  recognized  in  pulmonary  infarcts. 
Schloffer  records  instances  in  which  bullets  entering  the  heart  or  great 

1  Miller,  "Amer.  Med.,"  Aug.  2,  1902.  De  Grotibe,  "Revue  de  Chir.,"  1895, 
vol.  XV.  MacCallum,  "Amer.  Med.,"  March  21,  1903,  p.  452.  Riethus,  "Deut. 
Zeit.  f.  Chir.,"  Bd.  167.  Schloffer,  "  Beitr.  zur  klin.  Med.,"  vol.  xxxvii,  No.  3. 
Engel,  "Miinch.  med.  Woch.,"  June  25,  1901.  Claisse  and  Abrami,  "Soc.  mM. 
des  Hop.,"  April  14,  1905.  Gevele,  "Beitr.  zttr  klin.  Chir.,"  1904,  Bd.  43,  H.  2. 
Robinson,  "Med.  Record,"  Jan.  14,  1905.  Greene,  "Amer.  Jour,  of  Med.  Sci.," 
Dec,  1904.  Dearborn,  "Annals  of  Gynecolog}^  and  Pediatry,"  Boston,  Novem- 
ber, 1904.  Richter,  "Arch.  f.  Gyn.,"  1904,  vol.' 74,  No.  i.  Oswald,  "Zeit.  f.  klin. 
Med.,"  1904,  Bd.  53.  De  Quervain,  "La  Semaine  Medicale,"  1904,  xiv.  No.  41. 
Moynihan  and  Dobson,  "Practitioner,"  Oct.,  1904,  p.  538.  Schloffer,  "Zeit.  zur 
klin.  Chir.,"Bd.  37.  Fibiger,  "  Nordiskt  Mediciniskt  Arkiv"  (Stockholm),  March 
10,  1900.  Hodlmoser,  "Zeit.  f.  Heilkunde,"  1904,  Bd.  xxv,  H.  5,  p.  109.  Con- 
nell, Amer.  Med.  Assoc,  Section  in  Surgery,  June  10,  1904.  Wolf,  "Virch.  Arch.," 
Dec  I,  1903,  Bd.  174,  p.  454.     Schulz,  Inaug.  Diss.,  July,  1903,  Berlin,  No.  58.' 


ClkCULATUkY   DISTURBANCES.  27Q 

vessels  have  been  carried  along  with  the  blood-stream,  and  have  oc- 
cluded vessels.  (6)  Certain  parasites,  such  as  the  echinococcus,  filaria, 
etc.,  are  transported  by  the  circulating  blood. 

Thrombi  or  emboli  are  sometimes  spoken  of  as  (i)  arterial,  (2)  venous, 
or  (3)  capillary:  multiple;  miliary;  traumatic;  neoplastic,  arising  from 
tumors;  specific  and  nonspecific;  simple  and  malignant:  these  terms 
require  no  further  dctinition. 

Occasionally,  an  embolus  arising  in  the  venous  system  passes  directly 
from  the  right  to  the  left  side  of  the  heart,  through  a  defect  in  the  septum 
between  the  auricles  or  ventricles,  in  which  case  it  is  spoken  of  as  a 
paradoxic  or  crossed  embolus.  In  very  rare  instances,  as  a  result  of 
sudden  alterations  in  the  blood-pressure  affecting  only  one  area,  emboli 
may  float  backward  in  the  venous  stream,  producing  what  is  known  as 
recurrent  embolism,  or  they  are  called  retrograde  emboli.  This  was,  at 
one  time,  assumed  to  explain  certain  abscesses  of  the  liver,  which  are 
now  known  to  be  due  to  emboli  arising  in  the  portal  system. 

The  most  important  classification  of  emboli  is  the  division  into 
simple  and  infective,  the  terms  having  the  same  meaning  as  already 
given  when  considering  thrombi. 

Clianges  Induced  by  an  Embolus. — An  embolus  floats  along  in  the 
blood-stream  until  it  reaches  the  bifurcation  of  a  blood-vessel  either 
branch  of  which  is  too  small  to  transmit  the  mass,  or  until  it  enters  a 
vessel  the  progressive  narrowing  of  which  soon  leads  to  its  impaction; 
it  obstructs  or  arrests  the  stream,  and  commonly  leads  to  the  formation 
of  a  thrombus;  the  blood-supply  transmitted  by  the  occluded  vessel 
is  arrested,  and  the  area  beyond  suffers  from  the  altered  circulators- 
conditions.  The  changes  that  take  place  in  the  affected  area  vary  in 
degree,  and  are  greatly  influenced  by  a  number  of  factors,  among  which 
may  be  mentioned  the  character  and  size  of  the  embolus,  the  functional 
importance  of  the  tissue  involved,  the  presence  or  absence  of  an  abundant 
collateral  circulation,  and  the  possibility  of  secondary  infection  or  of  a 
primary-  infection  in  a  simple  necrotic  area.  With  regard  to  the  char- 
acter and  size  of  the  embolus,  it  may  be  said  that,  as  a  rule,  massive 
emboli,  such  as  dislodged  throml)i  of  considerable  size,  are  likely  to 
obstruct  the  circulation  of  an  area  that  may  be  sufficiently  large  at  once 
to  induce  alanning  symptoms  or  immediately  fatal  results.  Thus. 
emboH  of  considerable 'size  thrust  into  the  pulmonary  arterv'  may  lead 
to  almost  instantaneous  death.  For  the  production  of  this  result  it  is 
not  necessarv  that  the  circulatory  arrest  be  dependent  upon  the  occlu- 
sion of  a  large  trunk;  the  scattering  of  a  considerable  number  of  small 
emboli  (an  embolic  shon'cr)  brings  al)Out  exactly  the  same  result.  The 
shape  of  an  embolus  mav  l)e  such  as  only  partly  to  obstruct  a  blood- 
vessel, and  therefore  not  at  once  to  cut  off  nutrition  to  the  area  beyond. 
Soft  emboli  plug  vessels  more  completely  than  the  more  solid  ones. 
which  do  not  so  readilv  mold  themselves  to  the  vessel  lumen. 

The  functional  importance  of  the  tissue  involved  scarcely  m^nts 
more  than  mere  mention.     Thus,  it  will  be  evident  that  a  smal' 
involving  cutaneous,  subcutaneous,  or  allied  structures  mav 
little  change  as  to  escape  detection,  while  an  emlxilus  of  • 
involving  either  the  coronary  artery  or  a  cerebral  an-  •   • 
functions  of  great  importance  might,  in  either  case. 
death.     The  suddenness  with  which  symptoms  maniu-.     ;..w, -.....,  .. 


28o 


GENERAL  PATHOLOGY. 


also,  to  a  certain  extent,  dependent  upon  the  importance  of  the  tissue 
involved.  The  possibility  of  at  once  establishing  sufficient  collateral 
circulation  to  supply  nutrition  to  the  area  determines,  to  a  large  extent, 
the  character  of  the  subsequent  changes.  With  the  sudden  stoppage 
of  circulation  the  distal  portion  of  the  artery  empties  itself  of  blood, 
and  an  area  of  ischemia  is  thereby  induced.  The  sudden  and  per- 
sistent diminution  in  the  intracapil'lary  pressure  favors  the  influx  of 


Fig.  ISO. — Scheme  Illustrating  the  Formation  of  an  Anemic  Infarct  by  Obstruction  of  a  Terminal 
Artery. — {Chantemesse  and  Podwyssolsky.) 

a.  Embolus  occluding  arterj-.  b.  Branch  of  trunk  given  off  above  embolus,  c,  Artery  of  small  caliber  supplying 
the  tissues  adjacent  to  those  nourished  by  the  occluded  artery,  with  the  capillaries  of  which  there  is  scanty 
anastomosis,  d,  Vein  draining  the  affected  area.  The  bracket  from  the  letter  e  indicates  boundaries  of  the 
anemic  or  white  infarct.  /,  Zone  King  between  the  anemic  infa/ct  and  adjacent  tissue;  in  the  outer  margin  of 
this  area  the  process  of  repair  is  inaugurated,  or,  if  the  infarct  has  been  due  to  an  infected  embolus,  it  is  at 
this  point  that  the  contest  between  infection  and  liWng  tissues  wiU  be  most  active. 


blood  from  adjacent  capillaries  whose  contained  blood  is,  as  a  matter 
of  course,  directed  in  the  line  of  least  resistance.  Coincident  with  the 
changes  just  mentioned  dilatation  of  anastomosing  or  collateral  arteries 
occurs,  increasing  the  amount  of  blood  traveling  through  those  vessels. 
When  the  anastomosis  between  the  artery  involved  and  the  arteries 
whose  circulation  still  remains  intact  is  sufficiently  free,  there  is  quickly 
formed  a  circulation  adequate  to  maintain  the  nutrition  in  the  previ- 


CIRCULATUKY   OlSTi;  U  H  AN'CES.  -     . 

ouslv  ischemic  area.  Witli  the  estalihshment  of  suflicient  collateral 
circulation  the  nutrition  and  function  of  the  area  may  be  resumed, 
while  the  chanj^es  that  take  place  in  the  lodged  embolus  may  V>e  [)rac- 
ticallv  those  already  consitlcred  when  discussing  the  changes  to  which 
a  thrombus  is  liable. 

In  the  absence  of  a  sufficient  circulation  in  the  area,  degenerative 
or  necrotic   processes  occur.      In    tin-   brain,   in    the   spleen,   and.   to   a 


Fig.  isi.— Scheme  Illustrating  the  Formation  of  a  Hkmorrhagic  Infarc  r  as  a  Result  or  OB»T«ucni.N 
IN  a  Terminal  .\rtery.— (C/ian/<-»n-J5<-  and  Poduyssolsky.) 


a.  Embolus  occluding  the  artcrv.     6,  Hranch  of  arter>-  RJvcn  off  nt-'ivr  pmlxilm 
conliKUOus  tissue,  the  capillarii-s  of  which  arc  continuous  wi' 
the  atlected  area;    as  a  result  of  the  arterial  occlusion  and  f.ii: 
artery  there  may  tx;  a  slight  alllux  of  hlcKxl  from  the  vein 
of  conical  infarct  which  on  section  is  wcdKc-shapcd. 


'    '  '        '    'in  draininc 

X  pluurd 

/.   Wxac 


certain  extent,  in  the  kidney,  there  is  not.  beyond  a  given  point,  a 
liberal  anastomosis  between  the  blood-vessels  of  adjacent  areas.  Such 
blood-vessels  are  said  to  be  terminal:  this  implies  that  the  tree-like 
branches  given  off  bv  one  vascular  stem  do  not  communicate  freely 
with  similar  branches' of  adjacent  vessels.  The  plugging  of  such  vessels 
is  followed  bv  death  (necrosis)  of  the  area  involved,  which  is  now  calWl 
an  infarct.     When  the  area  remains  ischemic  (anemic  or  white  infarct), 


GENERAL  PATHOLOGY. 


the  uncomplicated  necrotic  process  presents  the  changes  already  de- 
scribed when  considering  coagulation  necrosis.  The  area  is  wedge- 
shaped  on  section — truly  cone-shaped,  with  the  apex  of  the  cone  corre- 


FiG.  152. — Part  of  Spleen  the  Seat  of  Multiple  Anemic  Infarcts. 

sponding  to  the  point  of  embolic  obstruction  and  the  base  directed 
toward  the  surface  of  the  organ.  This  typical  cone  shape  is  greatly 
modified  by  the  presence  of  even  a  moderate  degree  of  anastomosis 


Fig.  133. — Kidney.    Multiple  Anemic  Infarcts. 
Case  of  ulcerative  endocarditis. 


at  the  periphery,  and  in  large  infarcts,  or  when  multiple  infarcts  join, 
it  may  not  be  present.  The  consistence  of  the  tissue  is  dependent 
upon  the  amount  of  coagulable  material  present.     When  the  necrotic 


CIRCULATOKY   DlSTURBANfl  - 


area  lias  l)een  infiltrated  vvitli  lymph  from  the  a<ijaccm  ii-  -nc,  the 
swelling  and  increased  density  may  l>e  conspicuous.  If  the  area  be 
very  large,  the  center  may  undergo  fatty  degeneration  (prol)ably  li(|uc- 
faction  necrosis,  or  it  may  be  autolysis)  and  may  soften,  converting  it 
into  a  cyst;  when  liquefaction  necrosis  has  followed  the  coagulative 
processes,  the  fluid  can  be  absorbed  and  cicatrization  may  ensue. 
When  the  area  is  smaller,  repair  not  uncommonly  takes  place. 
Proliferation  of  the  connective-tissue  elements  occurs,  resulting  in  the 
production  of  embryonic  tissue  and  finally  in  cicatrization;  into  this 
lime  salts  may  be  inliltrated. 

During  the  progress  of  the  necrotic  processes  the  resistance  of  the 
tissue  to  infection  is  greatly  reduced,  and  not  infrequently  an  infarct, 
resulting  from   a  simple   embolus,   may   develop   suppuration.      If  the 
necrosis  is  so  situated  as  to 
offer  favorable  opportunities 
for  infection,  the  chances  of 
its    occurrence    are    greatly 
increased. 

The  foregoing  description 
applies  to  the  anemic  infarct 
and  to  the  process  spoken 
of  as  a)iemic  injarction.  In 
some  instances,  after  a  vary- 
ing period  of  anemia  the 
capillaries  of  an  ischemic 
area  become  overdistended 
with  blood,  admitted,  for 
the  most  part,  through  adja- 
cent communicating  capil- 
laries,or, slightly,  if  at  all, by 
venous  regurgitation ;  from 
the  congested  capillaries  ex- 
travasation of  blood  into 
the  connective  tissue  occurs, 
and,  in  addition  to  the  coag- 
ulation necrosis  in  progress 
in  the  cellular  elements  of 
the  area,  a  further  fibrinous 
matting  together  results 
from  the  associated  hem- 
orrhagic infiltration.  The 
resulting  change  constitutes 

a  hemorrhagic  infarct,  and  the  process  terminating  m  its  lurmaiion  is 
known  as  hcmorrha'^ic  injarction.  The  shape  ot  the  area  is  not  altered 
by  the  occurrence  of  hemorrhagic  infiltration.  The  swelling,  however, 
is  more  marked;  the  color  is  dark  red,  at  times  almost  black  a-v! 
the  density  is  greatlv  increased  by  the  presence  of  the  co 
blood.  The  subsequent  changes  are  the  same  as  those  occurnng 
of  anemic  infarction.  . 

It  has  been  held  that  an  anemic  or  white  infarct  is  but  a  lat- 
of  the  hemorrhagic  form  and  that  it  is  dependent  upon  the 
of  the  blood  coloring-matter  from  the  latter.'    It  is  possible  tl. 


Fig.  154.— LtNG,  HKUoRmiAcic  iNFAurr  (Xati«ai.  Sur.) 
.1.  Pleura.     B.  SmM  infarct  centrally  placed.      The  Urjje  in 
farct  shows  the  elevation  of  the  pleura,  the  hrmorrhajpc  Mjf 
fusion  of  ihc  central  area,  ami  the  pcri|>hcry  of  intUmm.-»tor> 

llVI«Tcnii.T. 


•  r    tt  ri  Iff 


11. II     Ml<   II 


284  GENERAL  PATHOLOGY. 

a  change  occurs,  and  that  the  results  of  the  two  processes  may  be  the 
same;  but  certain  infarcts  are  clearly  anemic  from  the  beginning,  and 
others  are  hemorrhagic  early  in  their  development. 

The  changes  revealed  by  the  histologic  examination  of  the  necrotic 
tissue  will  not  be  exactly  the  same  in  different  stages  of  the  process. 
They  are  practically  those  already  mentioned  when  considering  coagu- 
lation necrosis.     (See  p.  251.) 

In  emboli  containing  bacteria  (infective  emboli),  and  in  those  con- 
taining the  specific  cellular  elements  of  tumors  (neoplastic  emboli), 
arrest  is  followed  by  the  development  of  the  morbid  process  whose 
etiologic  factor  they  transmit.  If  the  embolus  contains  pyogenic 
organisms,  an  abscess  is  engendered;  by  reason  of  the  constant  pres- 
ence of  these  abscesses  in  pyemia,  they  have  long  been  known  as  pyemic 
abscesses.  By  reason  of  the  fact  that  such  abscesses  appeared  to  change 
their  location,  they  were  called  metastatic  abscesses.  Emboli  containing 
tubercle  bacilli  induce  tuberculosis  at  their  point  of  lodgment.  It  is 
probable  that  amebic  abscesses  in  the  liver  arise  as  the  result  of  emboli 
containing  amebae  brought  from  the  intestinal  lesion.  A  tumor  infiltra- 
ting the  wall  of  a  blood-vessel,  particularly  a  vein,  may  have  swept  into 
the  circulation  small  fragments  that  projected  into  the  blood-stream, 
and  these,  in  turn,  arrested  in  the  distant  capillary,  may  resume  their 
growth  and  give  rise  to  a  secondary  tumor  nodule,  or  metastatic  growth. 
From  the  infected,  parasitic,  and  neoplastic  emboli  secondary  thrombi 
may  form,  from  which,  again,  additional  emboli  may  be  broken  off  to 
continue  the  process  of  dissemination. 


I 


i'ii.\I'ti:k  XI. 

INFLAMMATION  AND  REPAIR. 

INFLAMMATION.' 

Probably  the  most  acceptable  defmition  of  iiillanimation  is  that 
given  by  Park,  which  is,  as  he  states,  a  moditication  of  one  suggested 
by  Sutton:  "Inflammation  is  an  exjiression  of  the  effort  made  by  a 
given  organism  to  rid  itself  of  or  to  render  inert  noxious  irritants  arising 
from  within  or  introduced  from  without."  It  is  probaljle  that  inflam- 
mation represents  the  process  of  repair  plus  (i)  infection  or  (2)  the 
removal  of  dead  tissue,  a  relationship  to  be  further  brought  out  when 
considering  the  causes  of  inflammation. 

Etiology. — As  just  indicated,  inflammation  is  ordinarily  jjroduced  by 
irritation  or  injury.  The  forms  that  these  factors  may  assume  are  mani- 
fold, and  any  attempt  to  enumerate  the  various  etiologic  elements 
leading  to  inflammatory  manifestations  would  lead  far  beyond  the  con- 
templated scope  of  the  present  article.  The  surgical  tendency  to  con- 
sider inflammation  as  always  the  result  of  infection  can  scarcely  be 
considered  justifiable.  After  all,  infection  acts  only  by  destroying  the 
cells  or  irritating  them  by  the  noxious  products  of  bacteria.  It  is 
true  that  bacteria  are  the  most  frequent  irritants,  and  that  a  large 
percentage  of  the  inflammatory  processes  arises  as  a  result  of  bacterial 
activity.  Bacteria  or  their  products  destroy  or  irritate  the  cells,  and 
manifest  a  peculiar  action  upon  the  fixed  and  migratory  cells  of  the 
economy,  thereby  inducing  inflammatory  processes  more  or  less  con- 
stant for  each  particular  species  of  organism.  The  activity  of  the 
inflammatory  processes  induced  by  bacteria  depends  upon  one  of  two 
factors:  (i)  the  pathogenic  power  of  the  germ  in  question;  (2)  the 
degree  of  susceptibility  of  the  tissues.  As  an  example  of  the  first 
condition  it  will  be  noted  that  if  the  two  ears  of  a  rabbit  be  inoculated 
with  the  anthrax  bacillus  or  with  the  streptococcus  i)yogenes.  using 
germs  that  are  somewhat  attenuated  in  one  ear.  and  a  more  virulent 
organism  for  the  other,  there  will  be  a  decided  difference  in  the  local 
reaction  as  manifested  in  the  two  organs.  Many  experiments  con- 
ducted along  this  line  have  led  to  conclusive  proof  that  the  pathogenicity 
determines  to  a  large  degree  the  activity  of  the  ensuing  inflammatory 
process.     The  importance  of  the  second  factor  in  the  production  of 

'  For  a  full  comprehension  of  inflammation  ever>-  student  shr^nM  rmtl  >frtrh 
nikoff,   "Comparative  Pathologj'  of    Inflammation"  (EnRlish    t- 
Adami,      Allbutt's  System  of  Med.,"   iRo«.  v<^l    i.  p    m       B-  • 
Hosp.  Jour.."  June,   1904,  p.   yoi.     Ch.i' 
essus    G^neraux,"  1905,    vol.  ii,  p.  333. 
Patholog\-  of  Inflammation,  Infection  .1 
"  Berlinr'klin.    Wfch."   Oct.    i,    1900. 
Pathology-,"   1900.     From  these  the  oMi 

285 


286  GENERAL  PATHOLOGY. 

inflammation  is  equally  well  established.  The  susceptibility  of  the 
tissues  may  be  augmented  by  reduced  vitality,  associated  irritation, 
b}^  the  absence  of  immunity,  either  inherited  or  acquired,  and  by  cir- 
culatory disturbances,  or  certain  perversions  of  the  nervous  system. 
The  susceptibility  of  an  animal  to  a  given  infection  undoubtedly  varies 
at  different  times — a  fact  well  shown  by  the  occurrence  of  severe  in- 
flammatory processes  after  most  trifling  injuries,  which,  under  other 
conditions,  apparently  give  rise  to  little  disturbance. 

Injury  to  the  tissue,  whether  it  be  mechanical,  chemic,  or  thermal, 
is  followed  by  the  occurrence  of  the  phenomena  of  inflammation;  the 
extent  and  severity  of  the  inflammatory  process  are  dependent  upon 
a  number  of  associated  factors.  As  just  indicated,  infection  truly 
represents  a  chemic  injury  to  the  tissue,  the  noxious  irritant  being 
the  specific  product  of  the  infecting  organism.  Inflammation  may  be 
induced  by  the  injection  of  bacterial  products  without  the  presence 
of  bacteria.  Here  the  tissues  are  dealing  with  chemic  bodies  alone.  As 
further  evidence  of  the  phlogistic  power  possessed  by  chemic  bodies  may 
be  cited  the  inflammation  induced  by  the  subcutaneous  introduction  of 
calomel,  turpentine,  croton  oil,  and  similar  irritants.  That  such  inflam- 
mations are  not  purely  of  experimental  production  is  established  by 
their  occurrence  after  the  use  of  powerful  antiseptics  in  too  concentrated 
a  form.  There  can  be  no  doubt  that  the  abundant  use  of  mercurial 
solutions  in  wounds^a  frequent  procedure  in  early  antiseptic  sur- 
gery— led  to  necrosis  of  a  large  number  of  cells  and  to  the  occurrence 
of  a  certain  degree  of  inflammation.  Recognizing  this,  surgeons  have 
adopted  asepsis  whenever  possible.  Even  in  infected  areas  abundant 
flushing  with  sterile  fluids  has  been  found  to  be  attended  with  less 
local  reaction  than  the  use  of  even  mild  antiseptics.  In  a  compara- 
tively frequent  form  of  conjunctival  inflammation  in  the  new-born, 
evidently  the  cause  has  not  been  the  microorganism  usually  present 
(gonococcus),  but  the  vigorous  use  of  agents  directed  toward  its  de- 
struction. In  this  instance  and  in  those  previously  given  the 
inflammation  arises  as  the  result  of  cell  destruction  brought  about  by 
agents  directed  toward  the  prevention  of  infection  or  toward  the  re- 
moval of  existing  organisms.  The  destruction  of  tissue  and  the  pro- 
duction of  exudates  by  chemic  agents  is  further  illustrated  bv  the 
tissue  reactions  resulting  from  the  application  of  so-called  counter- 
irritants,  such  as  mustard,  cantharides,  turpentine,  and  chloroform,  all 
of  which  induce  an  inflammatory  response.  Wounds  of  all  kinds 
involve  destruction  of  a  varying  number  of  cells  and  injury  to  others. 
The  wound  made  by  the  sharpest  instrument  is  marginated  by  a 
layer  of  lacerated  cells.  The  more  extensive  the  wound,  the  greater 
the  number  of  cellular  elements  involved;  and,  of  course,  injuries  made 
by  dull,  tearing,  vulnerating  bodies  contain  more  lacerated  cells  than 
wounds  of  like  extent  made  by  sharp,  clean-cutting  instruments. 

It  will  be  observed  that  the  whole  list  of  inflammatory  causes 
embraces  at  every  turn  the  destruction  of  cells.  The  destroyed  cells 
at  once  become  irritants  and  induce  inflammation  in  the  adjacent 
viable  tissues.  The  simple  aseptic  inflammatory  reactions  differ  from 
the  septic,  in  that  the  latter  contain  destructive  agents  that  are  con- 
stantly increasing,  and,  hence,  the  inflammatory  processes  seen  in 
wounds,  made  under  aseptic   conditions,   are  but   trifling   as   compared 


INFLAMMATION   AND   KKPAIk.  387 

with  the  extensive  inflammations  following  destruction  of  tissue  asso- 
ciated with  the  introduction  of  infective  agents  that  themselves  further 
extend  the  cell  necrosis  and  actively  antagonize  the  process  of  repair. 
For  this  reason  the  surgeon  has  been  led  to  regard  repair  as  dissociated 
from  inflammation,  and  to  say  that  aseptic  wounds  heal  without  inflam- 
matory phenomena.  The  pathologist  must,  however,  recognize  that 
all  tissue  injuries  are  attended  by  a  certain  amount  of  cell  destruction, 
and  that  the  effort  made  by  the  tissues  to  rid  themselves  of  the  dead 
elements  constitutes,  in  a  certain  way,  a  part  of  the  reparative  process. 
Still,  with  this  admission  before  us,  it  is  necessary  to  remember  that 
the  essential  phenomena  of  inflammation  and  the  essential  phenomena 
of  repair  are,  to  a  certain  extent,  dissimilar.  Inflammation  is  attended 
by  cell  necrosis  and  degeneration;  and  repair  by  cell  proliferation  and 
regeneration.  The  possible  admixture  of  the  two  processes  can  not 
be  gainsaid.  Of  course,  the  same  cellular  elements  at  a  given  point 
are  not  evincing  both  processes,  but  one  may  be  in  close  proximity  to 
the  other.  The  periphery  of  an  inflammatory  area  nearly  always 
shows,  in  the  absence  of  rapid  extension,  a  marginal  zone  of  reparative 
effort.  Were  the  effort  at  repair  to  remain  quiescent  until  inflammation 
had  terminated,  repair  would  probably  become  an  impossibility. 

Morbid  Anatomy. — The  lesions  to  be  studied  in  inflammation  are: 
(i)  The  changes  in  the  blood-vessels;  (2)  intravascular  changes,  or 
those  occurring  in  the  vessel  contents;  and  (3)  changes  in  the  peri- 
vascular tissues. 

Changes  in  the  Blood-vessels. — These  can  be  observed  in  any 
vascular,  transparent  membrane,  such  as  the  tongue,  mesentery,  or 
web  of  the  hind  foot  of  a  frog  or  the  mesentery  of  a  suitable  warm- 
blooded animal.  If  such  transparent  tissues  be  so  arranged  as  to 
permit  of  their  examination  under  the  microscope,  the  following  changes 
can  be  obser\'ed: 

At  the  beginning  of  the  examination  the  normal  capillary  presents 
itself  as  a  transparent  tubule,  within  which  can  be  seen  the  circulating 
blood.  As  a  rule,  the  application  of  an  irritant  is  not  necessan,- ;  expo- 
sure to  the  air,  with  the  associated  trauma  incident  to  the  arrangement 
of  the  tissue,  will  usually  bring  about  the  modifications  to  be  observed. 
In  other  instances,  as  in  the  web  of  a  frog's  foot,  it  may  be  necessary 
to  snip  off  with  the  scissors  a  thin  layer  of  the  epithelial  covering,  care- 
fully avoiding  any  wound  to  the  underlying  blood-vessels.  The  blood 
vessels  at  once  contract,  and  at  the  same  time  the  current  is  markedly 
accelerated;  this  phenomenon  is  of  brief  duration,  often  persisting  but 
a  moment,  and  within  the  first  hour  after  the  injury  the  brief  period 
of  contraction  will  be  followed  by  beginning  dilatation.  At  first  the 
dilatation  is  regular;  it  then  becomes  varicose,  and,  in  more  marked 
cases,  saccular  projections  of  the  capillary  wall  may  be  observed. 
Capillaries  at  first  not  recognizable,  or  at  least  not  transmitting  blood. 
dilate  and  become  more  or  less  distended.  A  similar  dilatation  of  the 
arterioles,  and  particularlv  of  the  venules,  is  also  seen.  The  changes 
so  far  observed  are  probably  due  to  increased  capillary  tension 
and  to  the  influence  of  the  noxious  agents  directly  upon  the  vessel 
wall.  The  rise  in  capillar)-  tension  is  probably  brought  about  by  re- 
laxation of  the  arterioles  through  which  the  blood-supply  to  the  part 
is  admitted.     The  increased   amount  of  blood   present   in   tlic  area  is 


288  GENERAL   PATHOLOGY. 

evident  to  the  unaided  eye.  It  is  not  possible  at  this  stage  to  recognize 
any  structural  alterations  in  the  cells  that  compose  the  capillary  wall, 
nor  are  we  able  to  see  any  enlargement  of  the  capillary  stomata,  or 
any  separation  of  the  endothelial  plates.  A  study  of  properly  fixed 
preparations  usually  shows  that  the  endothelial  cells  are  swollen,  and, 
when  the  process  has  lasted  for  any  length  of  time,  there  is  not  un- 
commonly evidence  of  degeneration  or  proliferation,  depending  upon 
the  activity  of  the  noxious  agent. 

Changes  in  the  Blood  and  Blood-current;  Intravascular  Changes. — 
Before  the  manifestation  of  inflammatory  phenomena  the  stream 
within  the  capillary  can  be  seen  to  be  composed  of  two  parts:  (a) 
An  axial  stream,  composed  of  the  corpuscular  elements  of  the  blood, 
and  therefore  spoken  of  as  the  corpusctdar  stream;  (6)  a  circumferential 
or  parietal  stream,  composed  of  blood-plasma,  and  hence  called  the 
plasmatic  stream.  During  the  period  of  acceleration — a  period  that 
corresponds  to  the  contraction  and  beginning  dilatation  of  the  capil- 
laries— these  two  clearly  differentiated  divisions  of  the  capillary  con- 
tents are  easily  recognized.  With  further  dilatation  and  beginning 
slowing  of  the  current  the  axial  stream  widens  and  the  plasmatic  stream 
grows  correspondingly  thinner.  Within  the  first  hour  or  so  the  nar- 
rowing of  the  plasmatic  stream  becomes  marked,  and  instead  of  re- 
maining clear,  it  contains  a  progressively  increasing  number  of  leuko- 
cytes.^ At  first  these  leukocytes  roll  along  the  vessel  wall;  later,  they 
become  attached  at  some  point  and  hang  off  into  the  slowing  stream 
as  pear-shaped  bodies,  the  small  end  of  the  pear  corresponding  to  the 
point  of  attachment.  The  margination  of  the  leukocytes  is  conspicuous 
in  the  small  veins,  but  the  size  of  even  the  larger  dilated  capillaries 
does  not  render  the  demonstration  easy.  As  the  dilatation  of  the  blood- 
vessel becomes  more  marked  there  is  poured  out  into  the  perivascular 
tissues  a  fluid  derived  from  blood-plasma;  this  fluid  constitutes  the 
liquid  exudate.  Along  with  this,  certain  of  the  leukocytes,  as  the  result 
of  their  ameboid  movement,  pass  through  the  vessel  wall  and  reach 
the  perivascular  tissues.  During  the  dilatation  of  the  blood-vessel  the 
blood-current  becomes  slower  and  slower,  the  corpuscles  manifesting  a 
slight  progression  only  with  each  heart-beat,  and  eventually  the  collected 
mass  of  cells  oscillates  in  the  capillary  lumen;  finally,  this  oscillation 
is  arrested,  and  stasis  or  stagnation  occurs.  Before  this  final  stage  the 
differentiation  into  the  axial  and  peripheral  streams  has  disappeared, 
and  the  cellular  contents  of  the  vessel  appear  to  occupy  the  entire 
lumen.  With  the  occurrence  of  stasis  the  red  corpuscles  at  points 
arrange  themselves  in  columns  composed  of  cells  piled  upon  one  another 
like  superimposed  coins  (rouleaux).  Migration  of  the  leukocytes 
continues,  and  many  of  these  cells  present  in  the  stagnant  blood 
move  toward  the  periphery  and  eventually  reach  the  perivascular 
tissues.  In  properly  fixed  specimens  the  leukocytes  can  be  seen 
in  various  stages  of  di^pedesis.  At  first  a  pseudopod  is  projected 
through  the  capillary  wall,  appearing  on  the  exterior  as  a  small, 
roundish,    knob-like    protuberance.     The   extravascular  portion   of  the 

^Before  attempting  to  follow  the  various  steps  of  migration  and  the  functions 
of  the  leukocytes  in  inflammatorv"  and  reparative  processes,  the  student  is  advised 
to  familiarize  himself  with  the  table  describing  and  differentiating  the  leukocytes. 
(See  Chapter  I,  of  Part  III.) 


INKLAMMATIDN    AM)   RKPAIK.  28g 

cell  increases  in  size  by  the  more  fluid  protoplasm  llowing  through 
the  narrowed  portion  into  the  extravascqlar  projection.  Finally,  the 
nucleus  passes  through,  and  apparently  the  solution  in  the  continuity 
of  the  vessel  wall  disappears.  (See  Fig.  155.)  After  the  migralicm 
of  the  leukocytes  and  the  lessening  of  the  intracaj)illary  tension  by 
the  pouring-out  of  the  exudate,  resumption  of  circulation  mav  be  at 
times  observed. 

To  a  certain  extent   the  character  of   the  irritant  determines  the 
form  of  leukocyte  most  abundant  in   the  exudate.      In  many  of  the 
infections,    and    particularly    in   pyogenic    infection,    the    polymorpho- 
nuclear leukocyte  (finely  granular  oxyphile  cell  or  microphagocyte)  is 
abundant.     In  other  inflammatory  conditions  the  hyaline  cell  (macro- 
phagocyte)  is  most  numerous.     The  most  numerous  cell  may  be  the 
small  mononuclear,  or  lymphocyte;    rarely  eosinophiles  are  present  in 
any    considerable   number.     Exactly   what    factors   determine    the  oc- 
currence of   one  or    the  other  of   these  cells    has    not    been  definitely 
ascertained.      It  would  seem,  however, 
that  in  the  more  acute,  and  particu- 
larly in  the  suppurative,  inflammatory  "  ^j         i        u  ?.^ 
conditions,  as  already  stated,  the  micro-                       ,        1^ 
phagocyte  is  the  cell  that  responds  to           ''"         |^     (y^     ?**^       *^ 
the  chemotactic  influence  exerted  by                     *      /^        '^' 
the     irritant;      in    the    more    chronic 

lesions,  with  less  active  irritants,  the        ^^  ^  ^    g^      p  •       ^ 
macrophagocyte    is    in  excess.      It    is      ^. '  •  ■ ''^    '" -' 

not  possible  to  affirm,  however,  with  /^ 

anv  degree  of  definiteness,  in  the  pres-  *         "^         **  *"m%nuu 

en{  stage  of  our  knowledge,  exactly  ^''=-  '"-^^rs^a^iam^c^,.''"""-'-'"""-^ 
what  conditions  determine  the  presence  Extending  out  from  the  sj.ic  of  the  leukocyte 
of  one  or  the  other  of  these  phagocytes.  S'ud^^T.  ^T^''-'  ""'"'''"  '  ■  S 

As   to   the   causes   leading   to   the  non  pf^  the  leuko. .  ,i. 

.  .  o  vessel  wall   in   in;i   ■  lo- 

occurrence  of   migration    and   to    the  pods  are  first  the 

development     of     the     exudate,     two  in^^.'hTi^'.i  t, 

views   have   been   held.     It  was  long  nucleus,  thcrei.v  drhvmiv  >)..■  .,11  up..n 

.  p  the  outer  side  of  a  blood-vessel  wall. 

maintained  that  it  was  purely  a  physi- 
cal   process;     the    increased    vascular 

tension,  with  the  associated  alterations  in  the  capillary  wall,  led  to 
the  escape  of  part  of  the  fluid  contents  of  the  vessel.  By  this  theory 
the  vessel  wall  was  presumed  to  be  passive.  Later  investigations  have 
led  to  the  adoption  of  an  entirely  different  opinion.  Under  the  older 
view  it  was  believed  that  the  fluid  normally  present  in  the  lymph- 
spaces  of  the  various  tissues  was  filtered  through  the  vessel  wall  as 
a  result  of  the  intravascular  tension.  Later  observers  hold  that  the 
endothelium  of  the  capillary  secretes  this  fluid,  and  that  instead  of 
being  a  transudate,  as  originally  thought,  it  is  purely  a  secretory  product 
of  the  endothelium.  Admitting  the  correctness  of  this  view,  the  material 
that  we  have  been  considering  as  an  exudate  must  now  be  regarded 
as.  at  least  in  part,  a  secretion.  The  technical  difficulties  that  attend 
efforts  to  demonstrate  the  correctness  of  either  theory  have  been  so 
great  that  neither  is  at  present  deemed  fully  acceptable.  The  theon,' 
that  the  migration  of  the  leukocytes  is  dependent  upon  increased  vas- 
cular tension  can   not.  of  course,  be  maintained,  as  wandering  cells 


2go 


GENERAL  PATHOLOGY. 


<J    ^  ^ 


^ 


Fig.  156- 

Polvmorphonuclear     leukocytes     from    center   of   one 

'  of  the  infiltrated  areas  in  a  section  of  the  cerebral 

cortex  and  meninges  from  a  case  of  suppurative 

meningitis.      Section  stained  with  toluidin-blue.^ 

(Zeiss  yV-inch  oil  immersion;  Queen  oc.  B.) 


already  present  in  the  tissues  adjacent  to  an  inflammatory  area  show 
migration  toward  the  center  in  spite  of  the  fact  that  such  migration 
must  be  in  the  direction  of  the  point  of  greatest  pressure. 

Changes  in  the  Perivascular  Tissue. — In  the  perivascular  tissues  two 
distinct  classes  of  elements  must  be  considered:    (i)    Changes  occurring 

in  the  elements  normally  present; 
-^    /">  (2)    changes    that    follow   in    the 

'^^  fluids  and  cells  coming  from  within 

^^        '    ■T^  the   vessels.     It  has   been   stated, 

^         -^^  and     apparently     correctly,     that 

»1:  changes  occurring  in  the    normal 

^    *«'  Jj^         perivascular  structures  are  essen- 

^f-         't?  tially  the  same    as  those   seen  in 

ei    "^  tissues    that    are    normally    avas- 

'^<5^    ^_    .  cular.     As  a  type  of  such  tissue, 

"     ?"'         the  cornea  may  be  studied.     The 
<^;  corneal  tissue  is  abundantly  sup- 

,.!  plied     with    lymph-channels,    but 

■^  contains  absolutely  no  blood-ves- 

;V  sels.       The     lymph     circulating 

through  the  corneal  lymph-spaces 
is  derived  from  the  capillary  circu- 
lation surrounding  the  organ.  De- 
struction of  a  small,  superficially 
placed  central  area  of  the  cornea 
by  means  of  chemic  irritants,  or 
the  removal  of  a  thin  superficial  layer  is  followed  by  opacity  at  the 
point  of  injury,  extending  as  a  zone  of  haziness  for  some  distance  be- 
yond. The  preliminary  degenerative  changes  in  the  corneal  corpuscles 
are  quickly  followed  by  reparative  efforts. 
Leukocytes    surround  and    eventually  in-  ^^ 

filtrate    the    area,  while    the   undestroyed  ^^        ,^ 

connective-tissue  cells  (corneal  corpuscles)       ^    -^  '@    ©  '^ 
begin   to   show   evidence   of   proliferation.       *^'  '■-  '  ^    0    ,. 

The   proliferative  changes    in  the  corneal        ^j^^.    m.   '^        g>.     ^ 
corpuscles  are  evidently   the    initial  steps         ®    ^         O         @     ^■ 
in  the  process  of  repair.     The  leukocytes       q,     ,3    ^  ^       . 

present  in  the  area  could  not  have  arisen  \,  ©  @' 

as  a  result  of  increased  pressure  directed  ;#  i#}  ^'  .@:  .@  .0. 
toward  the  point  of  injury,  but  must  be 
present  as  the  result  of  some  other  factor. 
This  leads  us  to  discuss  causes  inducing 
the  evident  migration  of  leukocytes  toward 
the  area  of  injury. 

De  Bary  observed  that  certain  Plasmo- 
dia moved  toward  the  nutritive  material 
placed  in  their  vicinity,  and  a  further  study 
showed  that  at  least  three  classes  of  sub- 
stances could  be  recognized:  (i)  Substances  toward  which  the  Plas- 
modia moved;    (2)   substances   that   did    not   seem    to    influence    the 

1  The  microscopic  drawing  made  from  this  section  Mall  be  found  in  the  chapter 
on  Diseases  of  the  Nervous  System,  under  the  head  of  Suppurative  Meningitis. 


w 


Fig.  157. 
Mononuclear  cells  from  meninges  in  a 
case  of  tuberculous  meningitis.  Sec- 
tion stained  with  toluidin  -  blue. 
(Zeiss  yV-inch  oil  immersion;  Queen 
oc.  B.)  ' 


INI'I.AMMATION    AM)    KKI'AIK. 


2t)  I 


orp:ani.sm;  (3)  suLstan^es  l"rt)in  which  the  organism  rccfdci.  This 
property  o{  colluhir  attraclion  and  repulsion  is  called  chemotaxis,  or 
chemiotaxis.  Wiien  the  cell  is  evidently  drawn  toward  the  body, 
the  condition  is  called  positive  chemotaxis;  when  repelled,  negative 
chemotaxis.  Positive  chemotaxis  is  admitted.  Ncj^ative  chemotaxis 
interests  us  but  little;  the  existence  of  such  a  condition  has  been 
doubted,  although  experimental  evidence  would  indicate  its  occasional 
occurrence.  Experiments  show  that  leukocytes  travel  toward  certain 
infecting  bodies,  and  that  dead  tissue  is  apparently  attacked  by  these 
cells.  The  ultimate  explanation  of  chemotaxis  is  still  wanting;  we 
do  not  know  whether  it  is  a  chemic  affinity  or  a  phenomenon  allied  to 
diffusion  in  simpler  bodies,  or  whether  it  is  an  essential  characteristic 
of  certain  cells  not  dependent  on  known  chemic  and  physical  ex- 
planations applicable  under  what   seem   to   be  similar  circumstances. 

The  cells  influenced  by  positive  chemotaxis  arrive  at  the  area  of 
irritation  from  tw^o  directions:  from  the  blood-vessels  the  polymorpho- 
nuclear leukocytes  migrate  in  large  numbers,  while  from  the  same 
source  and  also  from  the  adjacent  connective-tissue  spaces  come  the 
large  hyaline  cells  and  eosinophiles.  Eventually,  the  held  of  observation 
becomes  so  clouded  by  the  cellular  elements  present  that  continued 
study  of  the  previously  transparent  tissue  is  no  longer  possible.  Whether 
all  the  leukocytes  present  in  the  area  came  from  the  sources  just  indi- 
cated or  \vhether  some  of  them  are  the  result  of  proliferation  has  not 
been  definitely  determined.  It  is  reasonable  to  conclude,  from  data 
at  hand,  that  a  certain  number  of  the  leukocytes  may  result  from  pro- 
liferation of  migrated  cells.  That  this  number  is  large,  or  that  prolifera- 
tion constitutes  an  important  process  in  the  production  of  the  large 
numl)er  of  migrating  cells  present,  seems  doubtful. 

Recent  studies  of  the  cells  migrating  in  inflammatory  processes 
show  clearly  that  irritants  of  different  kinds  or  diflerent  intensities  of 
action  have  each  more  or  less  specificity  in  the  manifestation  of  their 
chemiotactic  power.  The  pyogenic  bacteria  attract  polymorphonuclear 
leukocytes;  the  toxins  of  the  tubercle  bacillus,  except  when  in  a  con- 
centrated form,  lead  to  accumulations  of  mononuclear  cells,  and  in  a 
general  way  the  same  is  true  of  the  poison  of  syphilis.  Reference  has 
already  been  made  (p.  207)  to  the  fact  that  in  the  presence  of  certain 
animal  parasites  eosinophile  leukocytes  become  unusually  numerous 
in  the  circulating  fluid.  A  knowledge  of  these  facts  has  been  turned  to 
diagnostic  purposes;  exudates  rich  in  polymorphonuclear  cells  may 
safely  be  looked  upon  as  due  to  pyogenic  irritants.  The  presence  of 
mononuclear  cells  suggests  tuberculosis  or  syphilis.  Serous  accumula- 
tions (transudates)  contain  no  more  polymorphonuclear  cells  than  will 
be  found  in  an  equal  rjuantityof  fluid  from  anyother  part  of  the  body, are 
also  })oor  in  mononuclear  leukocytes,  but  contain  numerous  endothelial 
cells  derived  from  the  membrane  lining  the  serous  cavities  or  lymph- 
spaces.  Diagnosis  by  an  examination  of  the  cellular  content  of  inflam- 
matory' exudates  is  called  cytodiagnosis.'     It  has  been  shown  to  have 

'The  important  clinical  aspects  of  cyt'  ''^.   "Le 

Cytodiagnostic."  Paris.  1903.     The  following  :  Froin, 

"C.  R.  Soc.  de  Biol.,"   ioo.j.  p.   1901.     LaV»bc.      La  i'n.s..-   .\t.  10. 

1904,  p.  505.  Barjon  and  Cade.  "Arch.  Gen.  de  M<|jd.."'  Auk  ''0- 
Beattie,  'Jour,  of  Path,  and  Bact.,"  June,  1902.  vol.  viJi.  N-'    - 


292  GENERAL  PATHOLOGY. 

considerable  value,  but  its  limitations  have  also  been  demonstrated. 
It  is  well  known  that  tubercle  bacilli  in  unusual  numbers  or  of  ex- 
ceeding virulence  lead  to  suppuration  (accumulation  of  polymor- 
phonuclear leukocytes).  The  same  organisms,  however,  in  numbers 
commonly  found,  give  rise  to  the  accumulation  of  mononuclear 
cells  (mononucleosis).  Cytodiagnosis  has  been  most  used,  and  the 
results  found  the  least  fallacious,  in  the  examination  of  exudates  in  the 
serous  cavities,  particularly  the  meninges,  pleura,  peritoneum,  joints, 
and  tendon-sheaths.  It  has  its  advantages,  but  can  not  be  relied  upon 
implicitly,  as  was  at  first  believed. 

In  many  conditions  the  cell  most  abundant  in  the  exudate  is  also 
found  increased  in  the  body-fluids,  particularly  the  blood.  Potymorpho- 
nuclear  leukocytosis  (polymorphonucleosis)  is  found  in  many  inflamma- 
tory processes,  particularly  those  in  which  exudates  containing  large 
numbers  of  these  cells  occur.  Diseases  due  to  certain  animal  parasites 
are  attended  by  hemal  increase  in  the  eosinophiles  (eosinophilia).  In 
malaria,  syphilis,  and  sometimes  in  tuberculosis,  the  mononuclear  cells 
of  the  blood  are  unusually  abundant.  This  feature  of  infections  is 
further  considered  in  the  chapter  dealing  with  the  pathology  of  the  blood.* 

The  changes  that  take  place  in  the  fixed  cells  of  the  tissues  involved, 
as  well  as  the  alterations  that  the  invading  cells  may  undergo,  are  de- 
pendent upon  a  number  of  conditions.  If  the  irritant  be  active, — as, 
for  example,  the  poison  of  virulent  bacteria, — many  of  the  cells  are  at 
once  destroyed.  When  the  pathogenicity  of  the  irritant  is  less  marked, 
degenerative  changes  may  be  more  conspicuous  than  actual  cell  death. 
The  characters  and  degree  of  the  degenerative  and  necrotic  changes  vary 
in  different  tissues,  and  are  more  marked  in  organs  whose  cellular  consti- 
tuents are  largely  of  epithelial  origin.  In  the  liver  and  kidney  the 
degenerative  phenomena  that  attend  inflammation  may  be  more  con- 
spicuous than  the  exudate.  In  such  epithelial  structures  cloudy  swell- 
ing, fatty  degeneration,  and  hydropic  distention  of  the  cells  with  nu- 
clear fragmentation  and  necrosis  may  be  conspicuous.  In  the  connective 
tissues  mucoid  and  hyaline  transformation  may  be  present.  The  amount 
of  degenerative  change  and  the  associated  cellular  disintegration  are  also 
dependent  upon  the  intensity  of  the  irritant;  such  degenerations  are 
most  marked  in  the  various  infections  of  which  the  pyogenic  constitutes 
a  typical  example. 

The  fluid  exudate  now  present  in  the  perivascular  tissues  varies  in 
quantity  and  composition.  The  quantity,  and  to  a  certain  extent,  the 
chemic  composition,  are  dependent  upon  the  character  and  strength  of 
the  irritant  as  well  as  upon  the  tissue  involved.  The  more  richly  vas- 
cular the  area,  as  a  rule,  the  greater  the  amount  of  the  exudate.  Loose 
connective  tissues,  such  as  the  eyelid,  scrotum,  and  labia,  show  marked 
accumulation  of  exudative  fluids.  The  same  is  commonly  true  of  serous 
membranes,  and,  to  a  lesser  degree,  of  the  subcutaneous  and  submucous 
connective  tissues.     The  fluid  differs  in  chemic  composition  from  the 

Jour,  of  Dermat.,"  Jan.,  1904,  p.  7,  Feb.,  1904,  p.  63.  Schwarz,  "Wien.  klin. 
"Woch.,"  Nov.  3,  1904,  p.  1 173.  Wolff  and  Tordaj^  "Berlin,  klin.  Woch.,"  Dec. 
5,  1904.  Leuchs,  "Virch.  Arch.,"  July  i,  1904,  Bd.  177,  p.  28.  Hektoen  and 
Ruediger,  "Jour,  of  Infectious  Diseases,"  1905,  vol.  ii,  No.  i,  January  12,  pp.  128- 
141.  Lewkowicz,  "Wien.  klin.  Woch.,"  Sept.  15,  1904,  p.  979.  Miller,  "Trans. 
Chicago  Path.  Soc,"  May  9,  1904,  vol.  vi,  No.  5. 
^  See  Leukocytosis  and  Leukopenia. 


INFLAMMATION   AND   KlCPAIk.  293 

iluid  in  edema;  its  specific  gravity  is  higher  (cdfina,  about  1.005  ^^ 
1.015,  rarely  over  1018;  inllamiiiatory  exu(hite,  1.015  to  1.025);  '^  '^ 
highly  albuminous,  not  uncommonly  containing  live  times  the  quantity 
of  protcids  j)rcsent  in  edema  lluids;  it  is  rich  in  fibrin.  When  bacteria 
are  present,  the  Iluid  usually  contains  jieptone,  whiih,  in  old  supimrativc 
processes  or  when  the  lesion  is  extensive,  may  enter  the  general  cinula- 
tion  and  may  be  excreted  in  sufficient  quantity  to  be  recognizable  in 
the  urine.  For  evident  reasons  the  inflammatory  exudate  is  rich  in 
cells,  an  abundance  of  which  may  render  the  fluid  fjuite  opaque. 

The  leukocytes  brought  into  the  area  by  any  of  the  processes  indi- 
cated at  once  attack  the  infecting  organism, — if  bacteria  be  the  cause  of 
the  inflammation, — or  proceed  to  remove  the  dead  tissue  when  the 
inflammatory  process  is  associated  with,  or  has  arisen  secondary  to, 
cellular  destruction.  The  phagocytes  active  in  this  process  have  been 
mentioned.  As  already  stated,  when  considering  phagocytosis  in  its 
connection  with  immunity,  it  is  not  improbable  that  certain  i)hagocytcs 
liberate  antitoxic  or  bactericidal  bodies  which  exert  a  certain  amount 
of  influence  in  subduing  infection.  (See  Phagocytosis,  p.  98,  and  Phago- 
lysis,  p.  99.) 

The  fluid  portion  of  the  exudate  relieves  the  intravascular  tension 
by  its  escape,  dilutes  the  irritant  present  in  the  tissues,  carries  with  it 
antitoxic  and  bactericidal  properties,  and  possibly  in  some  instances 
affords  increased  nutrition  (?)  to  the  cells  of  the  area.  The  fibrin-form- 
ing bodies  contained  within  the  exudate  reaching  the  periva.scular 
tissues  give  rise  to  fibrin,  which  acts  not  uncommonly  as  a  limiting 
body,  retarding  the  dissemination  of  bacteria  and  lessening  the  rapidity 
with  which  the  toxic  substances  present  are  diffused  into  the  surround- 
ing tissues.  Its  function  in  the  repair  of  wounds  will  be  considered 
later. 

Terniiiiations  of  the  Iiiflatiuiiatory  Process. — These  are  largely  de- 
pendent upon  the  activity  and  |)ersistence  of  the  cause,  as  well  as  upon 
the  susceptibility  of  the  tissue,  including  under  this  term  the  activity 
of  the  protective  agencies  whose  tendency  is  always  directed  toward 
the  arrest  of  irritant  action.  When  the  etiologic  factor  is  readily  over- 
come, or  is  quickly  withdrawn,  restitution  to  the  normal  may  be 
Ijrought  about  without  leaving  any  evidence  of  a  past  inflammation. 
In  the  early  stages  of  the  inflammatory  process  the  withdrawal  of  the 
cause  is  quickly  followed  by  absorption  of  the  exudate  and  the  re- 
establishment  of  the  circulation.  The  exudate  passes  off  by  the  lymph- 
atics or  is  taken  up  by  the  veins,  and  the  few  extruded  leukocytes 
re-enter  the  circulation,  either  directly,  through  the  blood-vessels,  or  in- 
directlv,  through  the  lymphatics,  eventually  leaving  no  recognizable 
tissue  alteration.  As  the  inflammatory  process  continues,  so  favoralilc 
a  termination  becomes  less  and  less  possible,  until  finally  the  tissue 
alterations  are  such  that  a  return  to  the  normal  is  no  longer  to  be  an- 
ticipated. Under  such  circumstances  the  occurrence  of  repair  is  the  best 
that  can  be  expected;  and  the  longer  such  repair  is  delayed,  the  less 
effectual  it  is  likely  to  be.  The  most  important  factor  in  the  preven- 
tion of  repair  is  infection;  and  the  more  active  this  infection,  the  more 
grave  the  tissue  alterations  will  be.  and  the  less  perfect  the  subsequent 
repair. 

Suppuration.— The    organisms    most    active    in    the    production    of 


294  GENERAL  PATHOLOGY. 

suppuration  are  the  staphylococci  and  streptococci — pyogenic  cocci. 
While  the  foregoing  are  the  usual  bacteria  active  in  suppurative  proc- 
esses, it  is  not  to  be  forgotten  that  many  other  organisms  share  this 
pus-producing  power.  Thus,  the  Bacillus  coli  communis.  Bacillus 
pyogenes  foetidus,  Bacillus  typhosus,  Gonococcus,  Micrococcus  cereus. 
flavus,  Micrococcus  cereus  albus,  Pneumococcus,  the  fungus  of  actino- 
mycosis. Bacillus  pyocyaneus,  Bacillus  anthracis,  and  other  organisms, 
occasionally  manifest  pyogenic  activity.  In  most  instances  suppura- 
tion is  due  to  mixed  or  concurrent  infection.  Commonly,  at  least  two 
organisms  are  present,  and  in  many  instances  a  number  may  be  asso- 
ciated. A  series  of  unpublished  investigations  conducted  by  Lockett  in 
the  writer's  laboratory  showed  that  of  one  hundred  consecutive  suppura- 
tive processes,  a  single  infection  was  the  exception.  These  observations 
are  corroborative  of  many  similar  studies  made  by  other  observers. 

Abscess. — In  infection  by  pyogenic  organisms  the  continued  action 
of  the  irritant  (a  necessary  sequence  of  bacterial  proliferation  and  of 
the  continued  production  of  toxins)  prolongs  the  period  of  exudation 
and  necrosis  and  increases  the  quantity  of  the  exudate,  which  is  particu- 
larly rich  in  phagocytic  cells,  the  most  abundant  of  which  is  the  finely 
granular  oxyphile  cell — the  polynuclear  or  polymorphonuclear  leuko- 
cyte. The  bacterial  products  lead  to  degenerative  and  necrotic  changes 
in  the  fixed  tissue  elements,  associated  with  liquefaction  of  the  inter- 
cellular substance,  converting  the  area  so  affected  into  a  mass  of  cellular 
detritus  in  which  the  cell  longest  retaining  its  morphologic  character- 
istics— the  polymorphonuclear  cell,  now  the  pus-corpuscle — is  most 
abundant.  It  has  usually  been  held  that  liquefaction  of  the  exudate 
depended  upon  the  peptonizing  influence  of  bacterial  products.  It  is 
probable,  however,  that  the  softening  and  subsequent  fluidification  are 
due  to  the^  activity  of  products  liberated  by  the  cells,  especially  the 
leukocytes,  and  therefore  present  in  the  fluids  of  the  affected  tissue.  In 
no  other  way  is  it  possible  to  account  for  the  abscess  formation  which 
results  from  the  introduction  of  purely  chemic  irritants.  The  studies 
of  Rulot^  and  others  have  demonstrated  that  the  leukocyte  contains 
bodies  through  the  action  of  which  fibrin  may  be  liquefied  and  other 
so-called  autolytic  changes  produced.  The  fluid  resulting  from  these 
changes  is  called  pus. 

Pus  is  a  creamy  liquid  possessing  a  faint,  sweetish  odor;  its 
specific  gravity  ranges  between  1.020  and  1.035,  with  a  mean  of  about 
1.032.  Essentiallv,  pus  is  composed  of  two  elements — the  fluid  and 
cellular  portions.  '  The  fluid  constituent  is  called  the  liquor  piiris;  it 
represents  the  serous  constituents  of  the  exudate,  to  which  has  been 
added  the  fluid  resulting  from  the  Hquefaction  of  the  intercellular 
substance  and,  possibly,  from  the  dissolution  of  a  number  of 
the  tissue  elements,  and,  it  may  be,  of  some  of  the  cells.  It  is  com- 
paratively rich  in  albumoses,  to  which  the  absence  of  coagulability 
has  been  attributed.  It  also  contains  leucin  and  tyrosin.  Binaghi^ 
has  demonstrated  the  bacteriolytic  and  to  a  certain  extent  the  antitoxic 
properties  of  pus.  An  animal  unusually  susceptible  to  an  organism — 
for  example,  the  anthrax  bacillus — may  escape  if  the  inoculation  be 
made   into   a   cavity  .  containing   pus ;  subsequent   examination   of   the 

1  "Arch,  intemat.  de  Physiol.,"  t.  i,  1904,  pp.  152-158. 
"^  "Rif.  Med.,"  May  4,  1904. 


INIW-AMMATION   AND   REPAIR.  395 

lluid  shows  that  inan\-  of  the  organisms  liave  disappeared.  That  the 
substances  antagonizinij  the  bacteria  are  present  in  the  pus  and  not  in 
the  body-fluids — at  least,  in  the  same  (juantity — is  indicated  by  the  fact 
that  the  same  animal  may  readily  be  infected  by  inoculation  through 
paths  that  do  not  bring  the  microl)C  in  contact  with  the  pus.  The  pus-cell 
is  richly  granular,  usually  polynuclear  or  polymf)rphonuclcar,  and  for  a 
brief  period  following  its  removal  from  the  body  may  manifest  well-marked 
ameboid  movements;  in  its  present  form  it  can  not  be  differentiated 
from  the  polymorphonuclear  or  rincly  granular  oxyphile  cell,  which 
earlier  reached  the  inflammatory  field  from  the  blood-vessel.  The 
experiments  of  Muir  show  that  a  cubic  millimeter  of  pus  may  contain 
a  million  leukocytes;  if  this  proportion  is  maintained,  thirty  cubic 
centimeters  (one  ounce)  would  contain  as  many  leukocytes  as  three 
and  a  half  liters  (120  ounces)  of  blood.  The  fact  that  during  the  evolu- 
tion of  an  abscess  the  number  of  leukocytes  in  the  blood  not  infrequently 
undergoes  a  constant  increase  indicates  the  enormous  leukocyte-pro- 
ducing capacity  of  the  body-tissues.  With  regard  to  the  hyaline  or 
mononuclear  cell,  occasionally  present  in  pus,  our  information  is  less 
satisfactory;  the  tendency  at  present  is  to  regard  these  cells  as  invaders 
from  the  adjacent  connective-tissue  spaces — in  other  words,  they  are 
believed  to  be  celomic  wandering  cells;  that  they  are  also  derived  from 

the  circulating  blood  seems  equally  established.  . 

In  the  production  of  an  abscess,  liquefaction  first  takes  place  at  the  j 
center  of  irritant  action,  from  which,  as  we  pass  outward,  toward  the 
surrounding  uninvolved  tissue,  all  intermediate  stages  of  the  inflam- 
matorv  process  may  be  recognized.  [jCJie  icall  of  the  abscess  is,  therefore, 
composed  of  the  normal  tissues  of  the  part,  showing  various  degrees  of 
inflammatory  infiltration,  degeneration,  and  necrosis.  The  zone  lying 
nearest  to  the  pus  is  composed  of  necrotic  tissue  rich  in  leukocytes. 
Surrounding  this  will  usually  be  seen  a  zone  containing  the  exudative 
fluids  and  numerous  white  blood-cells.  There  is  usually  present  more 
or  less  fibrin  entangled  among  the  fixed  connective-tissue  fibrils  and 
cells,  the  latter  not  uncommonly  showing  proliferative  changes.  In  this 
zone  efforts  at  repair  and  at  the  prevention  of  dissemination  may  be 
evident.  Externally,  this  zone  gradually  fades  into  the  normal  tissue,  and 
intemallv  it  is  continuous  with  the  necrotic  zone  to  which  reference  has 
already  been  made.  If  undisturbed,  the  abscess  tends  to  travel  along  tl:e 
path  of  least  resistance;  as  the  infective  agents  manifest  a  disjjosilion  to 
extend  in  all  directions,  but  are  met  by  the  protective  forces  of  the  tissues, 
the  path  of  least  resistance  must  be  through  those  tissues  where  the  pro- 
tective agencies  are  least  active.  The  vascularity  of  the  part,  and  hence 
the  richness  in  leukocytes,  usually  results  in  the  extension  of  the  abscess 
toward  the  surface,  'through  which  it  eventually  ruptures  and  dis- 
charges its  contents.  Relieved  of  this  tension,  the  direction  of  the 
fluid  exudate  is  now  strongly  toward  the  absicss  cavity.  This  results 
in  flushing  out  the  surrounding  lymph-spa.cs,  ami  favors  thp  artion 
of    the   protective  -forces— the   phagocytes,   antitoxic   and    1  Ul 

bodies  present  in  the  inflammatory  area.    When  the  infectiv<  ns 

are  destroved  or  rendered  inert,  the  liquefaction  necrosis,  leukinyte 
migration,' and  consequent  formation  of  pus  cease;  after  incision 
and  evacuation  the  walls  of  the  abscess  collapse,  and  reparative  efforts 
become  ascendant. 


296  GENERAL  PATHOLOGY. 

Ulceration. — The  younger  Gross  often  spoke  of  an  abscess  as  a  sub- 
cutaneous ulcer,  and  in  the  present  state  of  our  knowledge  many  ulcers 
could,  with  propriety,  be  called  superficial  or,  more  correctly,  exposed 
abscesses.  Where  suppurative  processes  are  so  situated  that  a  wall 
is  formed  on  but  one  side, — in  other  words,  are  exposed, — the  floor  of 
the  ulcer  is  structurally  quite  like  the  wall  of  an  abscess.  This  applies, 
of  course,  only  to  ulcers  in  which  infection  is  active.  Exposed  or  de- 
nuded subcutaneous  tissues  where  the  removal  of  the  overlying  struc- 
tures has  been  brought  about  under  strict  aseptic  precautions  bear 
little  resemblance  to  the  changes  observed  in  the  formative  stage  of  an 
abscess.  When,  however,  the  ulcer  has  resulted  from  infective  proc- 
esses, giving  rise  to  necrosis  of  the  overlying  structures,  the  early 
stages  of  ulcer  formation  are  practically  identical  with  those  seen  in  the 
wall  of  a  developing  abscess.  The  pus  formed  by  such  ulcers  finds 
ready  egress,  and  the  protective  powers  of  the  underlying  tissues  usually 
limit  and  arrest  the  spread  of  the  ulcerative  lesion.  Occasionally, 
however,  ulcers  show  continued  necrosis,  gradually  extending  in  one 
or  more  directions,  thereby  indicating  the  inefficiency  of  the  protective 
powers  in  the  adjacent  tissues,  or  extreme  virulence  on  the  part  of  the 
infecting  organisms;  in  such  cases  mixed  infection  is  the  rule.  The 
fact  that  such  ulcers  appear  to  extend  in  one  or  more  directions,  as 
though  something  were  eating  away  the  tissues,  led  to  their  being 
called  phagedenic. 

In  addition  to  abscess  formation  and  ulceration,  there  are  allied 
forms  of  infection  in  which  the  anatomic  peculiarities  of  the  tissues 
involved,  or  the  absence  of  resistance,  or  the  intensely  toxic  power  of 
the  infection,  give  rise  to  changes  resembling  abscess  formation,  but 
by  no  means  identical.  Closely  allied  to  abscess  formation  is  the  oc- 
currence of  suppurative  lesions  of  the  serous  membranes.  Here  the 
collection  of  pus  takes  place  in  the  serous  cavity,  and  is  not  usually 
referred  to  as  an  abscess.^  Suppurative  processes  leading  to  the  ac- 
cumulation of  pus  in  cavities  lined  by  epithelium  occur.  As  in  serous 
cavities,  these  are  not  usually  referred  to  as  abscesses;  thus,  a  purulent 
accumulation  in  the  pelvis  of  the  kidney  is  spoken  of  as  "pyonephrosis," 
and  in  the  Fallopian  tube  purulent  distention  is  called  "pyosalpinx." 

At  times  the  extension  of  infection  proceeds  with  such  rapidity  that 
a  distinct  accumulation  of  pus  may  not  be  evident.  Thus,  in  inflam- 
mation of  the  cellular  tissues,  and  in  inflammation  of  the  lymph-vessels 
(angio^leucitis)  due  to  virulent  infection  or  to  greatly  reduced  resistance 
on  the  part  of  the  individual,  the  inflammatory  process  may  extend 
with  remarkable  rapidity,  and  may  even  terminate  fatally  before  the 
occurrence  of  any  recognizable  purulent  collection.  Sometimes  along 
the  paths  of  such  rapidly  spreading  infections  a  variable  quantity  of 
macroscopically  recognizable  pus  may  be  developed.  Such  a  condition 
is  usually  referred  to  as  diffuse  suppuration,  suppuration  of  the  cellular 
tissues,  purulent  infiltration,  suppurative  cellulitis,  and,  without  any 
apparent  reason,  is  sometimes  called  purulent  suffusion. 

The  occurrence  of  gangrene  as  a  result  of  infection  has  already  been 
considered.^ 

^  For  the  description  of  suppurative  inflammation  of  serous  membranes,  see 
Disease  of  Serous  Membranes,  Part  III. 
^  See  Spreading  Gangrene,  p.  256. 


INFLAMMATION   AND  RETAIK. 


297 


The  terms  acute,  subacute,  and  chronic,  as  applied  to  inflammatory 
processes,  are  used  to  indicate,  to  a  certain  extent,  the  period  of  time, 
or  duration,  as  well  as  the  activity  of  the  inflammation,  and,  under 
certain  circumstances,  its  location  and  sequels.  That  form  of  chronic 
inflammation  in  which  the  process  extcnrls  over  a  long  period  of  time 
and  is  associated  with  the  formation  of  fibrous  tissue  in  excess  is  some- 
times referred  to  as  productive  inflammation.  The  changes  that  take 
place  in  the  interstitial  tissue  of  the  kidney  in  chronic  interstitial  neph- 
ritis may  be  taken  as  a  type  of  this  form  of  inflammation.'  The  view 
that  all  tissue  changes  associated  with  an  increase  in  fibrous  tissue 
are  to  be  regarded  essentially  as  manifcstatio'ns  of  productive  inflam- 


Fio.  158.— Kjdney,  Chronic  Lnterstitial  Nepurjtis. 
A.  Part  of  capsule.    5.   Malpinhian  Ixxly.  showinf?  arlvanrinR  gran   " 
ing  of  the  capsule.     C.  C.  C-    Tubules  in  the  miilst  of  the  n. 
is  wastetl  or  absent  and  tlic  tubular  wall  notably  thickened.      1 1 
what  dilated. 


mation  is  no  longer  strongly  urged.  Thus,  in  degenerations  that  involve 
parts  of  the  glandular  viscera  the  disappearance  of  the  essential  normal 
elements  may  be  followed  by  the  develo[)ment  of  hbrous  tissue.  This 
is  sometimes  spoken  of  as  "substitutive  fibrosis,"  and  by  some  is  not 
considered  to  be  an  evidence  of  past  or  existing  inflammatif>n  Such 
increase  in  fibrous  tissue  is  also  called  "noninflammatory  !  la." 

thereby   difTerentiating  it  from   the  increase  in   fibrous   ti  i  is 

clearly  consecutive  to  inflammation  and  constitutes  the  tcrmmal  tissue 
changes  in  many  inflammator>-  processes.     When  considering  the  path- 
'  See  Chronic  Interstitial  Nephritis,  chapter  on  Diseases  of  the  Urinan-  Or- 
gans, Part  III. 


298  GENERAL  PATHOLOGY. 

ology  of  organs,  fui^ther  reference  will  be  made  to  chronic  inflammatory 
processes  and  substitutive  fibroses.^ 

Inflammatory  processes  not  associated  with  infection  are  sometimes 
spoken  of  as  simple  or  common.  To  speak  of  such  processes  as  common 
in  the  sense  that  they  are  frequent  is  clearly  an  error,  as  most  inflam- 
mations are  due  to  infection.  Inflammations  due  to  some  particular 
organism  are  called  specific.  While  not  restricted  to  syphilis,  the  term 
specific  infection  is  most  frequently  applied  to  syphilitic  lesions.  When 
the  essential  secreting  or  actually  functionating  cells  of  an  organ  are 
involved,  the  inflammation  is  said  to  be  paroichy^natoiis ;  when  the 
supporting  tissue  (connective  tissue)  is  the  principal  seat  of  the  lesion, 
the  inflammation  is  called  interstitial.  By  reason  of  the  intimate 
physiologic  and  structural  relation  of  the  connective  tissues  of  organs 
with  the  essential  functionating  cells  it  does  not  seem  probable  that  an 
inflammation  can  ever  be  strictly  parenchymatous  or  strictly  inter- 
stitial. TJiat  one  or  the  other  tissue  may  be  apparently  more  involved 
justifies,  to  a  certain  extent,  this  nomenclature.  Suppurative,  pyo- 
genic, purulent,  or  phlegmonous  inflammations  have  already  been  con- 
sidered. Such  inflammations  are  appropriately  called  septic,  in  con- 
tradistinction to  the  infrequent  inflammatory  conditions  in  which  bac- 
teria have  no  part — aseptic  injiamviations.  When  considering  inflam- 
mations of  the  mucous  membranes,  reference  will  be  made  to  catarrhal, 
pseudomembranous,  fibrinous,  croupous,  diphtheric,  gangrenous,  sup- 
purative, and  hemorrhagic  inflammations  of  those  structures.^  Dry, 
moist,  serous,  serofibrinous,  fibrinous,  plastic,  adhesive,  exudative,  and 
other  inflammatory  processes  affecting  serous  membranes  will  be  con- 
sidered with  diseases  of  those  structures.^ 

It  will  not  be  amiss,  at  this  point,  briefly  to  discuss  the  cardinal 
symptoms  of  inflammation  and  to  indicate  the  relation  that  exists 
between  these  usually  recognizable  changes  and  the  morbid  processes 
to  which  they  owe  their  presence.  The  more  or  less  active  inflamma- 
tory conditions,  and  even  certain  inflammations  characterized  by  slug- 
gishness, possess  one  or  more  of  the  so-called  cardinal  symptoms:  namely, 
heat,  pain,  discoloration,  swelling,  and  disordered  function. 

Morbid  Physiology  of  Inflammation. — /.  Heat. — Practically,  the 
recognizable  rise  of  temperature  is  dependent  upon  the  increased 
amount  of  blood  distributed  in  the  area,  which,  coming  from  internal 
organs,  possesses  a  temperature  higher  than  the  blood  present  in  the 
superficial  circulation  under  normal  conditions.  Theoretically,  the 
following  features  are  also  active;  it  is  not  probable,  however,  that 
their  influence  is  of  practical  import:  (a)  the  increased  cellular  meta- 
morphosis; (b)  the  increased  oxidation  that  is  going  on  in  the  area  in- 
volved; (c)  the  friction  of  the  increased  blood-current  and  the  impact 
of  stasis  may  also  increase  the  temperature. 

2.  Pain  is  due  to  pressure  or  to  stretching  of  the  nerves  by  the  swell- 
ing, and  to  the  irritant  action  of  the  inflammatory  exudates  upon  the 
nerve  filaments.  At  this  point  it  is  well  to  note  that  pain  may  be 
beneficent  in  inflammation,  in  that  it  secures  rest  of  the  part,  thereby 
leading  the  patient  to  favor  the  progress  of  reparative  processes. 

'  See  Interstitial  Pneumonia  and- Cirrhosis  of  the  Liver,  Part  III. 
^  See  Diseases  of  the  Mucous  Membranes,  Part  III. 
'  See  Diseases  of  Serous  Membranes,  Part  III. 


INFLAMMATION"   AND  REPAIR.  299 

V  Di.'it.oloralion  is  dependent  upon  (a)  the  increased  amount  of 
blood  in  the  area;  (6)  the  proHferation  of  the  cellular  elements;  and 
(c)  the  character  of  the  inflammatory  exudate;  thus,  the  increased 
amount  of  blood  may  give  rise  to  redness,  whicli  becomes  scarlet,  brown- 
ish, or  bluish,  passing  through  the  different  shades  to  black;  the  color 
depends  on  the  vascularity  of  the  part  and  the  degree  of  stasis.  In 
nonvascular  exudates  the  structure  may  be  white  instead  of  red;  this  is 
showTi  in  the  cornea,  in  which  the  "ground-glass  appearance"  is  ob- 
served; this  gray,  lusterless,  cellular  accumulation  and  granular  change 
in  the  corneal  corpuscles,  as  the  cornea  is  avascular,  cause  no  red- 
ness. Redness,  when  present,  is  represented  by  the  injection  of  the 
adjacent  conjunctiva.  The  exudate  in  inflammations  of  serous  mem- 
branes renders  the  surface  white,  unless  the  inflammatory  processes  be 
hemorrhagic. 

4.  Sii'clli)ig  is  due  to  (t7)  the  increased  amount  of  blood  in  the  part; 
(b)  the  notable  accumulation  of  leukocytes  and,  to  a  much  less  degree, 
the  proliferation  of  cells;  {c)  undoubtedly  the  most  important  factor  is 
the  exudate  in  the  perivascular  tissue.  As  already  stated  when  con- 
sidering the  development  of  the  exudate,  sw^elling  may  manifest  beneficial 
tendencies.  Under  certain  circumstances  it  becomes  dangerous;  thus, 
if  the  swelling  be  great,  the  capillary  circulation  may  be  obstructed 
and.  as  a  result  of  faulty  nutrition  and  of  the  activity  of  the  inflamma- 
tory' process,  degenerative  changes,  necrosis,  and  even  gangrene  may 
occur.  This  unfortunate  termination  is  sometimes  obser\'ed  in  in- 
flammation of  the  subcutaneous  tissues  (cellulitis,  angioleucitis),  where 
the  extensive  swelling  cuts  off  nutrition  to- the  overlying  structures  and 
gangrene  ensues.  Inflammation  of  the  juxta-epiphyseal  disc  may  lead 
to  thrombosis  of  the  capillaries  supplying  the  epiphysis,  followed  by 
necrosis  of  that  structure.  It  is  not  necessary  to  multiply  examples, 
although  reference  should  be  made  to  the  corneal  sloughing  that  takes 
place  as  a  result  of  intense  swelling  of  the  surrounding  conjunctiva, 
cutting  off  ingress  and  egress  of  lymph  from  the  avascular,  transparent 
membrane. 

5.  Disordered  function  is  due  to  (a)  alteration  in  the  tissue  cells 
present,  both  the  essential  functionating  cells  and  the  interstitial  ele- 
ments; (b)  the  mechanical  interference  with  function  resulting  from 
the  exudates;  and  (c)  the  fact  that  the  exudates  impede  the  activity 
of  the  innervation  upon  which  the  function  of  all  tissue  so  largely  de- 
pends. 

Systemic  Phenomena  of  /H^ammn/ion.— These  are  largely  embraced 
in  the  term  fever,  and  are  due  to  the  absorption  of  bacterial  toxins  and 
other  poisons  engendered  bv  the  perverted  metabolism  and  necrosis  in 
the  affected  tissue.  The  character  of  the  fever  and  the  severity  of  its 
manifestation  are  dependent  upon  the  activity  of  the  agents  ab.sorbed. 
In  the  simple  aseptic  fluids  taken  up  by  the  ly  cs- 

sels,  from  an  ordinary  sterile  wound,  such  as  is  i  ne. 

the  manifestations  are   slight   and   temporary.     When   ih.  ib- 

stances  absorbed  contain  the  products  of  bacterial  life,  ma-  ra- 

tion in  the  tissue  elements  elsewhere  in  the  body  may  occur.  Degen- 
erative and  necrotic  lesions  are  produced  in  the  viscera  indr;  •''■•'!♦  of 
the  presence  of  bacteria.     The  disturbances  of  glandular  are 

represented  in  the  diminished  secretions  and  excretions.      1  m  ^ 


300  GENERAL  PATHOLOGY. 

Hal  surfaces  show,  under  the  influence  of  bacterial  agents,  a  decided 
tendency  to  undergo  degenerative  processes;  this  is  most  marked  the 
more  severe  the  infection,  so  that  in  the  gangrenous  and  specific  in- 
flammations— for  example,  those  of  diphtheria — coagulation  necroses 
in  the  large  glandular  viscera  are  not  uncommon.  The  nervous  phe- 
nomena that  accompany  inflammation  are  probably  due  to  the  direct 
action  on  the  nerve  substance  of  the  toxins  under  consideration,  or  to 
the  influence  of  the  poison  upon  the  capillaries  distributed  in  the  nerve 
tissues,  giving  rise  to  inflammatory  or  degenerative  processes  in  those 
structures.  Exactly  what  causes  the  condition  called  fever  will  be 
discussed  later. 


REPAIR.! 

Cell  Reproduction. — As  a  part  of  the  processes  of  repair  (repair 
modified  by  infection,  regeneration,  inflammation  so  called,  hyper- 
plasia, certain  forms  of  hypertrophy,  etc.),  prolification,  proliferation, 
or  reproduction  of  cells  must  be  studied.  There  are  two  methods  by 
which  cells  are  reproduced:  (i)  Direct  division,  or  amitosis;  (2)  indirect 
division,  also  known  as  karyokinesis ,  karyomitosis ,  and,  quite  commonly, 
a  more  convenient  term,  as  mitosis. 

1.  Amitotic  Division. — In  this  form  of  segmentation  the  cell  elon- 
gates and  develops  a  constriction  that  involves  both  the  cell  protoplasm 
and  the  nucleus.  This  constriction  is  followed  by  a  separation  of  the 
two  portions,  the  nucleus  first  dividing  and  passing  to  the  two  ends 
of  the  protoplasm,  which  gradually  separates,  giving  rise  to  two  cells; 
during  the  process  there  is  no  manifest  systematic  change  in  the  chro- 
matin of  the  nucleus,  as  is  seen  in  the  next  form. 

2.  Mitosis. — As  a  rule,  the  cell  divides  only  into  two  parts;  this  is 
not,  however,  constant,  as  occasionally  three  cells  may  be  developed 
simultaneously  from  one  cell  (J.  Arnold).  The  steps  of  mitosis  may 
be  approximately  stated  as  follows :  In  the  resting  nucleus  the  chromatin 
increases  and  groups  itself  as  a  skein,  which  later  becomes  thinner 
(mother  skein).  During  this  process  the  nuclear  membrane  disappears, 
and,  if  the  cell  possessed  a  nucleolus,  this  is  lost  sight  of.  Immediately 
following  this — probably  in  progress  at  the  same  time — there  are  de- 
veloped, apparently  from  the  achromatin,  delicate  lines  that  pass  ofif 
toward  the  two  poles  of  the  cell,  giving  the  central  portion  of  the  cell 
an  arrangement  shaped  like  a  spindle,  and  hence  the  name  nuclear 
spindle.  The  chromatin  now  divides  transversely  to  this  nuclear  spindle, 
and  passes,  one  half  in  each  direction,  toward  the  points  of  the  spindle. 
The  mass  of  the  chromatin  at  each  end  of  what  was  the  spindle  now 
constitutes  what  are  spoken  of  as  the  daughter  stars.     During  the  arrange- 

!  Maximow,  "  Experimentelle  Untersuchungen  liber  die  entziindliche  Neubil- 
dungen  von  Bindegewebe  " ;  Funfter's  Sup.  "Ziegler's  Beitrage,"  Jena,  1902.  Pez- 
zolini,  "Gazz.  Osp.  e  Clin.,"  1901,  No.  151.  Minervini,  "Virch.  Arch.,"  1904,  Bd. 
175,  Heft  2,  p.  238.  Jurgelunas,  "Ziegler's  Beitr.,"  1901,  Bd.  xxix,  Heft  i.  Mal- 
lory,  "Jour.  Med.  Research,"  Dec,  1903,  p.  334.  Capaldi,  Memor.  Chirurg.  Pal- 
ermo, 25th  year.  Hektoen,  "Jour.  Med.  Research,"  March,  1902,  n.  s.,  vol.  ii. 
Schiffmann,  "Centralbl.  f.  allg.  Path.,"  1903.  Schleifstein,  "Virch.  Arch.,"  March 
I,  1904,  Bd.  175,  Heft  3,  p.  534.  Taddei,  "Atti  Accad.  di  Sci.  med.  enat.  in  Fer- 
ara,"  1903,  Loeb,  "Jour.  Med.  Research,"  1902,  vol.  viii,  p.  109.  Matsokua, 
"Virch.  Arch.,"  Jan.  2,  1904,  vol.  175,  p.  32. 


INILAMMATION'    AM)   KKI'AIK. 


30 « 


nient  of  the  chromatii\  as  daugliter  stars  an  hour-glass-like  contraction 
of  the  |)roto])lasm  of  the  cell  appears,  formed  by  an  annular  narrowing 
gradually  tleveloped  around  the  center  of  the  cell.  At  tirst  the  daughter 
stars  situated  in  the  two  poles  of  the  cell  are  joined  l»y  delicate  striation, 
which  probably  represents  the  remains  of  the  achromatin  formerly 
constituting  the  nuclear  spindle;  these  lines  disai»pear,  the  two  masses 
of  chromatin  show  no  connection,  and  the  hour-glass  contraction 
is  completed,  separating  the  cell  into  two  parts,  each  of  which  contains 
a  daughter  skein,  which  now  rearranges  itself  as  a  resting  nucleus, 
around  which  a  new  nuclear  meml)ranc  may  appear. 

Lavdowsky  has  described  another  form  of  cell  division  that  he  calls 
dk'isioii  by  force.  It  ap]iears  in  this  form :  two  portions  of  the  proto- 
])lasm  of  the  cell  move  in  opposite  directions,  apparently  pulling  them- 


Close  skein  (viewed 
from  the  side). 
Polar  field. 


****p^v 


Loose  skein  (viewed  Mother  stars 
fronj  .above  :  i.e.,  (viewed  from 
from  the  pole).  the  side). 


Mother  star 
(viewed  from 
above). 


*  - 

Daughter  stars. 


(BeRinning.)       (CompUli^'n.) 
Oivisioii  of  the  prolupl.ism. 


Fig.  ISO.— Karyokijjetic  Figures  Observfd  i.n  the  EnxHEUUM  of  the  Mouth  Cavity  or  a  SALA»iA.vnr.«.— 

(Slohr.)     X   .s6o  diameters. 

The  picture  in  the  upper  ri(?ht-hand  comer  is  from  a  section  throuRh  a  dividing  cjrg  of  <«ircdon  pi»dfonni».     The 

centrosomata.  also  the  first  stages  of  the  development  of  the  spmdie,  can  not  be  seen  by  this  magnifiiation. 


selves   apart.     Thoma    has   described   and    illustrated    this   process   as 
occurring  in  the  white  r)lood-cells  of  the  frog  when  stmiulated  by  elec- 

tricitv.  .  ■   t      • 

Inflammation  is  repair  plus  the  removal  of  ilead  tissue  or  infection. 
When  there  is  no  dead  tissue  to  remove,  or  when  this  is  in  a  mmimum. 
and  when  there  is  no  infection,  injury  to  tissue  is  followed  immediately 
by  the  process  of  repair.  •      u    r  n 

As  studied  by  the  surgeon,  healing  is  said  to  take  place  m  the  tollow- 
ing  wavs: 

I.  Union  by  First  Intention.— Thus,  if  the  surfaces  of  .  '  nd 

be  brought  immediately  in  contact  and  retained,  the  foil  ;n- 

ena  occur:    Liquor  sangtiinis  containing  a  variable  numb*.:  Us 

fills  the  interstices  of  the  wound  and  extends  laterally  into  li- 


302 


GENERAL  PATHOLOGY. 


Spaces  of  the  wound  margins.  Coagulation  is  facilitated  by  the  presence 
of  thrombin  or  its  antecedents  formed  in  the  extravascular  tissues.  The 
resulting  coagulated  liquor  sanguinis — so-called  inflammatory  lymph 
or  fibrinous  cement — affords  a  temporary  binding  between  the  two  mar- 
gins of  the  wound,  affording  sufficient  solidity  to  permit  the  further  prog- 
ress of  repair.  The  first  step  necessary  is  the  removal  of  the  dead  cells 
and  other  structures  which  constitute  irritating  foreign  bodies ;  this  is 
accomplished  by  the  leukocytes  which  migrate  from  the  adjacent  lymph- 
spaces  and  vessels.  In  the  absence  of  infection  the  number  of  poly- 
morphonuclear leukocytes  is  small,  while  the  mononuclear  are  more 
numerous;  proliferative  changes  and  accumulating  mononuclears  give 
rise  to  a  tissue  made  up  of  round  or  irregular  cells  to  which,  on  account 
of  their  polymorphism,   Maximow  gives   the  name  polyblasts.     Many 

of  these  are  indistinguisha- 
ble from  the  lymphoid  cells 
(fa  c  ^.^^   large    hyaline   leuko- 

cytes, from  which  it  is 
probable  they  are  all  de- 
rived; they  are  identical 
with  the  small  round  cell 
or  indifferent  cell  of  the 
older  writers.  Among  these 
soon  appears  a  cell  appar- 
ently having  an  entirely 
different  destiny.  In  its 
younger  forms  it  may  re- 
semble the  poly  blast,  but 
soon  becomes  fusiform  and 
eventually  develops  into 
long  spindles,  from  the 
tapering  ends  of  which 
delicate  fibrils  can  be  seen 
extending  a  considerable 
distance  from  the  body  of 
the  cell;  this  structure  is 
called  the  fibroblast.  Ap- 
parently it  is  the  product 
of  proliferative  changes  in 
the  fixed  connective-tissue 
cells  of  the  part.  The  rela- 
tion of  the  newly  formed  fibrous  tissue  to  these  cells  renders  it  clear  that 
the  fibrils  are  in  some  way  developed  from  them,  but  exactly  how  the 
elaboration  of  fibrils  is  accomplished  is  less  certain.  Of  the  many  methods 
that  have  been  suggested,  ohree  are  deserving  of  consideration:  (i)  The 
older  view  that  the  fibrils  resulted  from  elongation  and  attenuation  of  the 
cell  protoplasm  followed  by  disappearance  of  the  nucleus  is  not  in  accord 
with  the  best  information  as  to  the  method  by  which  cells  ordinarily 
accomplish  the  specific  purposes  toward  which  their  activity  is  directed. 
(2)  According  to  this  view,  the  fibrils  are  formed  at  the  periphery  of 
the  cell  from  which  they  are  shaled  off  or  shed,  new  fibrils  arising  as 
rapidly  as  the  older  become  an  integral  part  of  the  developing  cicatrix. 
Eventually  when  the  fibrous  tissue  formation  is  complete  the  nuclei  of 


-/ 


Fig.  160. — Cellular  Elements  of  Formative  Tissue. — 
(Schmaus.)     X  500  diameters. 

a.  a.  Polyblasts.  b.  Mother  star.  c.  Daughter  star.  d.  Skein 
st.-ige.  e  Round  or  lymphoid  cells.  /,  /.  Polymorphonu- 
clear leukocytes. 


INK  LAM  MAT  ION   ANU   KIvl'AIK.  303 

many  ol  the  fibroblasts  disappear,  otliers  remaining  as  the  fixed  connec- 
tive-tissue cells  of  the  scar.  (3)  It  is  known  that  the  matrix  of  bone 
and  cartilage  is  formed  through  the  secretory  activity  "f  cells  (osteo- 
blasts or  chondroblasts)  and  tliat  most  other  cells  accomjjlish  function 
by  a  process  called  secretion.  In  order  to  coordinate  fibrogenesis  with 
osteogenesis  and  chondrogenesis  it  is  necessary  to  assume  that  the  fibro- 
blasts in  a  way  secrete  the  fibrils  forming  the  cicatrix;  in  other  words, 
that  the  cicatricial  tissue  is  laid  down  by  these  cells  exactly  as  the 
matrix  of  bone  or  of  cartilage  is  formed.  It  is  possible  to  see  in  some  of  the 
fibroblasts  a  periphery  of  fine  granules  which  by  intracellular  or  extra- 
cellular coalescence  might  readily  form  the  fibrils,  and  it  is  ])robable 
that  this  or  some  similar  method  is  ordinarily  followed  in  their  produc- 
tion. The  view  that  the  fibrils  are  shed  from  the  margin  of  the  cell  is  in 
accord  with  their  possible  secretion,  or  at  least  is  not  inconsistent  with 
that  origin. 

In  addition  to  the  cellular  elements  already  mentioned  as  present 
in  tissues  undergoing  repair  there  are  a  number  of  cells  the  nature  and 
function  of  which  are  not  accurately  determined.  Among  these  may  be 
mentioned  the  plasma  cell  and  the  giant  cells  of  repair.  The  plasma  cell 
is  about  the  size  of  the  lymphoid  or  hyaline  leukocyte,  it  possesses  a 
round  or  oval  nucleus  and  a  structureless  jirotoplasm  which  stains  with 
varying  degrees  of  intensity  when  exposed  to  the  action  of  basic  anilin 
dyes  (is  basophilic).  While  frequently  present  in  reparative  processes  it 
has  been  shown  by  Councilman  and  others  that  this  cell  constitutes  an 
important  element  in  the  interstitial  exudate  of  acute,  non-suppurative, 
interstitial  nephritis,  and  in  parenchymatous  inflammations  of  toxic 
origin  and  associated  with  cell  exudation.  It  is  probable  that  the  plasma 
cell  is  a  derivative  of  a  hemal  leukocyte,  possibly  the  lymphocyte, 
although  upon  this  point  additional  data  are  needed.  The  function 
and  fate  of  the  cells  are  also  undetermined.  Another  conspicuous  cell 
in  reparative  processes  is  a  large,  round,  oval  or  polymorphous  body, 
var\-ing  in  size  from  10  -/  to  40  "  or  50  //  and  containing  a  number  of 
nuclei ;  this  is  the  giant  cell  of  repair.  Such  elements  are  more  common 
in  tissues  containing  foreign  bodies,  but  are  not  proportionate  to  the 
size  or  number  of  extraneous  substances.  The  nuclei  are  less  commonly 
peripheral  than  in  the  giant  cell  of  tuberculosis,  and  the  protoplasm  is 
usually  less  intensely  acidophilic,  although  neither  of  these  differences 
is  constant.  The  origin,  mode  of  formation,  and  function  of  giant-cells 
have  been  the  source  of  much  controversy  since  their  description  by 
Johannes  Miiller  in  1S38.  They  probably  arise  in  one  of  two  ways: 
(i)  Nuclear  division  without  associated  protoplasmic  segmentation; 
(2)  confluence  of  the  protoplasm  of  cells,  resulting  in  the  formation  of 
a  type  of  giant  cell  resembling  that  cau.sed  b"  the  massing  of  other  cells, 
called  Plasmodia.  It  is  probable  that  the  second  is  the  more  common 
method  b^^  which  these  cells  are  produced.  The  number  of  nuclei  pres- 
ent in  the'  giant  cell  varies;  as  many  as  eighty  have  been  observed  in  a 
single  cell.  The  researches  of  Heidenhain,  Koch,  Metchnikoff,  Souda- 
kewitsch.  Faber.  Hektoen,  and  others,  fully  establish  the  inclusion  and 
phagocvtic  power  of  giant  cells. 

The'  foregoing  description  of  the  cytology  of  reparative  ti«;«fTie  has 
necessarilv   led   past   changes  in  other  structures,   not  nd- 

vessels.     During  the  early  avascular  stage  the  structr.  i  of 


304 


GENERAL  PATHOLOGY. 


leukocytes  and  polyblasts,  and  possibly  cells  ancestral  to  the  fibro- 
blast, has  been  called  indifferent  tissue,  embryonic  tissue,  or,  including 
the  later  stages,  productive  or  reparative  tissue.  The  name  embryonic 
tissue  is  based  on  the  supposition  that  constituent  cells  possess  capaci- 
ties for  growth  comparable  to  some  of  the  cells  seen  in  the  earlier 
stages  of  the  developing  embryo,  and  are  competent  to  produce  more 
than  one  kind  of  tissue,  for  example,  fibrous  tissue,  bone,  etc.  It  is 
probable,  however,  that  the  tissue  eventually  produced  is  dependent 
upon  the  origin  of  the  formative  cell;  when  these  structures  arise 
from  connective  tissue,  an  ordinary  cicatrix  is  formed;  when  they 
are  the  progeny  of  bone  cells,  they  give  rise  to  bone,  and  though  in 
both  instances  the  morphology  and  stain  reactions  render  them  indis- 


FlG. 


-Granulation  Tissue. 


Later  Stage  in  Organization  than  Figure  j6o.~(,Sii!maj(s.)     X  250 
diameters. 

a.  Round  or  lymphoid  cells,  b.  Fibroblasts,  c.  Spider  cells,  multipolar  cells,  d.  Space  from  which  ceOular 
elements  have  dropped  out;  possible  primitive  lyrnph-spaces.  e.  Point  where  the  evolution  of  fibrous  con- 
nective tissi\e  is  most  advanced.  /.  Leukocytes  with  seveial  nuclei.  Through  this  area  will  be  .seen  young 
capillaries,  branched  and  budding;  the  same  are  shown  below  the  blood-vessel  indicated  by  the  upper  g. 
5,  g.  Blood-vessels,    h.  Matrix  of  intercellular  sub.stance  forming  fibrillated  tissue. 

tinguishable,  the  tendency  to  elaborate  structures  identical  with  the 
mother  tissue  indicates  potential  differences. 

In  order  to  maintain  the  nutrition  of  the  developing  tissue  vascu- 
larization is  necessary.  While  in  the  embryo  other  forms  of  capillary 
development  are  recognized,  the  only  form  admittedly  present  in  re- 
parative processes  is  development  by  budding  From  the  walls  of 
the  nearest  capillaries  proliferating  endothelial  cells  give  rise  to  conic 
projections  which  extend  into  the  developing  tissue.  These  projecting 
buds,  after  passing  some  distance  from  their  point  of  origin,  unite 
with  other  buds,  thus  forming  capillary  loops,  through  which  the  circu- 
lation is  established.  The  tissue  previously  known  as  embryonic  tissue 
is  now  granulation  tissue.     When  seen,  for  example,  in  the  floor  of  an 


INFLAMMATION    AND   RKPAIR. 


305 


ulcer,  each  loop  or  group  of  loops  forms  a  minute  elevation  called  a 
granule;  hence  the  name  granulation  tissue.  It  is  possible  that  capil- 
laries formed  in  this  way  may  later  develoj)  thicker  walls,  and  may 
ultimately  become  arteries  or  veins.  Around  the  newly  formed  capil- 
laries the  development  of  fibrous  tissue  continues.  At  first  the  cicatrix 
is  red.  or  at  least  pinkish,  the  heightened  color  being  due  to  the  rich- 
ness of  its  blood-supply.  Later,  contraction  of  the  interlacing  fi- 
brous tissue  occurs,  diminishing,  by  pressure,  the  number  and  carrying 
capacity  of  the  newly  formed  vessels,  the  tissue  eventually  becoming 
white.  The  tendency  of  developing  fibrous  tissue  to  contract  gives 
rise  to  structural  and  functional  disturbances  in  organs  whose  nutrition 
it  so  profoundly  influences.  The  evidence  of  such  contraction  is  clear 
in  diseases  of  certain  viscera,  such  as  the  liver  in  chronic  interstitial 
hepatitis,  and  the  kidney  in  chronic  interstitial  nephritis. 

There  is  sometimes  descril>ed  a  fonn  of  repair  that  closely  resembles 
union  bv  first  intention — repair  upon  a  jramcwork  or  scaffold.  To 
illustrate  how  this  may  occur,  let  us  suppose  that  there  is  a  large  "dead 
space,"  such  as  would  re- 
sult from  chiseling  a  cavity 
in  bone;  into  this  dead 
space  blood  oozes  and  coag- 
ulates. The  fibrin  forms  a 
scaffold,  upon  w'hich  young 
blood-vessels  and  embryo- 
nic and  granulation  tissue 
advance  from  the  sides  and 
eventually  complete  the 
process  of  repair.  Mate- 
rials other  than  blood  have 
been  used  for  the  scaffold; 
sponge,  chips  of  bone,  car- 
tilage, ivory  fragments,  and 
allied  substances  that  can 
be  readily  antisepticized 
are  sometimes  used. 

2.  Healing  by  second  in- 
tention is  said  to  occur  in 

wounds  the  edges  of  which  can  not  be  brought  together,  and  in  which  the 
scaffolding  process,  already  referred  to,  is  not  available.  The  ordinary 
recent  traumatic  ulcer  is  an  illustration  of  this  process.  Suppose  that 
considerable  skin  surface  is  removed,  and  that  a  raw  surface  is  presented 
for  healing:  Within  a  few  hours  a  layer  of  coagulated  fibrin  and  partly 
inspissated  serum  appears  upon  the  surface  of  the  wound.  Dead 
elements  within  the  viable  tissue  are  attacked  by  the  phagocytes  and 
are  removed,  and  proliferation  of  the  connective-tissue  cells  and  accu- 
mulation of  leukocytes  proceed  to  the  formation  of  embr; 
formative  tissue.  'Young  capillaries  spring  out  from  the 
vessels  and  convert   the  formative  tissue  into  granule-  it.      liy 

continuous  proliferation  of  the  cellular  elements,  with  \  .     .p  of  the 

capillaries,   the   cavity   is   gradually  tillc<l.  and  when  this  new  tissue 
reaches  the  surface,  covering  over  by  epithelium  occurs. 

The  epithelial  regeneration  is  secured  through  the  activity  of  the 


Fio.  »6». 


Till-    lurm.ition 


i|.ill.iru' 


Endothili.il  pl.ites  wiili   iiroi. 
later  iK-conii:  i.ipill;irii-^.     <  11 
shown.    \  part  <>f  tlu-  v.-iMul.ir  I'-'p 
r,  r. — (Lanaoii.) 


.nt.iin-  r.-.l  tl.-.l 


3o6 


GENERAL  PATHOLOGY 


epithelial  cells  near  the  edge;  these  proliferate,  and  by  extension  from 
the  periphery,  in  favorable  cases,  gradually  cover  the  granulating 
surface.  Epithelium  may  be  ingrafted  upon  the  formative  tissue, 
and  additional  centers  of  epithelial  regeneration  may,  in  this  way,  be 
established. 

Another  form  of  healing  that  is  truly  repair  by  second  intention 
is  sometimes  referred  to  as  healing  by  third  intention.  This  is  illus- 
trated when  two  granulating  surfaces  are  brought  together;  the  two 
adhere,  blood-vessels  pass  from  one  to  the  other,  and  cicatrization 
occurs,  exactly  as  already  described.     The  final  cicatrization  and  ob- 


FiG.   163. — Section  Through  the  Border  of  a  He.\ung  Wound  (Diagrammatic). — (Rindfleisch  )     X  300 

diameters. 

a.  Surface  of  ulcer,  b.  Granulation  tissue  composed  of  embryonic  tissue  with  the  capillary  loops  developed  from 
the  vessels  below,  c.  Later  stage  in  the  development  of  the  granulation  into  spindle-cell  elements;  young 
cicatricial  tissue  that  is  older  at  d.     e,  /,  g.  The  epithelium  spreading  over  the  surface  of  the  healing  area. 


literation  of  an  abscess  cavity  is  secured  in  this  manner.  After 
evacuation  of  the  pus  and  destruction  of  the  bacteria  the  collapsed 
walls,  coming  in  contact,  unite.  It  was  once  considered  that  union 
under  a  scab  represented  another  form  of  healing,  but  it  is  now  recog- 
nized that  granulation  and  skinning  over  by  epithelium,  as  already 
described,  occur.  It  is  not,  therefore,  a  distinct  process,  but  merely 
a  form  or  combination  of  some  of  the  foregoing. 

A  close  examination  of  the  forms  of  repair  as  just  given  will  show 
a  distinct  resemblance  of  each  to  all  the  others;  the  difference,  so  striking 
clinically,  is  far  less  marked  when  we  come  to  investigate  the  essential 


INI-I.AMMATIoN'   AND   KKPAIR.  3O7 

changes  through  which  each  must  pass.  In  all  there  is  the  same  prepa- 
ration for  repair,  usually  etTectcd  through  the  activity  of  phn;-  • 
Following  or  accompanying  this,  ])roliferati()n  of  pre-existing  < 
leads  to  the  development  of  (ibrol)lasts,  through  the  presence  oi  v.  intii 
final  cicatrization  is  brought  about.  Kven  the  epithelial  regeneration 
is  not  essentially  anything  out  of  the  common,  as  wherever  the  skin 
has  lieen  wounded,  whether  the  injury  l»c  microscopic  or  large,  i»ro- 
liferation  and  extension  from  the  margin  must  be  the  only  normal 
method   of  covering  the  young  connective  tissue. 

Regeneration. — Repair  may  occur  without  regeneration.  Thus, 
muscle  may  be  repaired  by  fibrous  tissue,  the  scar  joining  the  severed 
ends  of  the  muscle.  It  does  not  seem,  however,  that  new  muscle  is 
produced,  certainly  not  in  quantities  of  material  value  in  the  restoration 
of  destroyed  areas.  With  regard  to  nerve  and  bone,  this  is  dilTerent; 
repair  terminates  in  regeneration,  and  new  tissue  may  be  i)roduced 
that  is  identical  with  that  previously  present.  Regeneration  occurs 
in  but  few  tissues;  nerve  and  bone  are  the  best  examples.  Repair 
seems  possible  in  almost  any  tissue,  but  such  repaired  tissue  may  be, 
in  part  at  least,  functionally  inactive,  because  regeneration  has  not 
been  complete.  Thus,  a  large  cicatrix  upon  the  skin  does  not  contain 
sweat-glands  or  hair-follicles,  and,  while  it  protects  the  subcutaneous 
tissues,  it  performs  none  of  the  special  functions  of  the  skin.  Destroyed 
kidnev  tissue  may  be  followed  by  repair,  but  apparently  not  by  re- 
generation. 

Manv    authorities    regard    regeneration    and    repair    as    es.sentially 
identical  processes;     thus,  when  repair  terminates  in  the  formation  of 
fibrous  tissue,   they  say  it  is  regeneration  of  the  fibrous  tissue.     No 
one  doubts  the  regeneration  of  fil)rous  tissue,  but  when  a  large  area 
of  the  skin  or  a  considerable  volume  of  an  organ   is  converted   into 
fibrous  tissue,   with  the  total  disappearance  of  every  other  structure 
but  the  fibrous  tissue,  it  certainly  is  not  correct  to  say  that  the  organ 
is  regenerated,   and  the  enormous  increase  in   fibrous  tissue  amounts 
to  something  more  than  the  mere  regeneration  of  that  element.     Repair, 
as  described  here,  is  synonymous  with  regeneration  of  the  fibrous  tissue 
described  by  other  writers.     Regeneration,  as  already  defined,  im:  '  • 
the    production   of  new  elements   structurally   and   functionally  ;<' 
to,  if  not  identical    with,    the  destroyed  tissue  that  they  replace.      1  :  • 
regeneration  of  nerve  and  l)nnf  is  considored  with  the  special  pathf)!'  .•,. 
of  those  structures.' 

*  See  chapter  on  Nervous  System  and  chaf)tcr  on  Diseases  of  Bones.  Part  1 1 1 


CHAPTER  XII. 
TUMORS. 

The  word  tumor,  which  means  swelling,  has  been  variously  applied 
in  medical  literature.  Some  writers  evidently  include  among  the 
tumors  cellular  collections  clearly  of  inflammatory  origin;  to  such 
aggregations  of  cells  is  given  the  name  inflammatory  tumors,  granu- 
lation tumors,  etc.  The  tendency  at  present  is  to  exclude  all  such 
masses  and  restrict  the  term  tumor  to — (i)  neoplasms;  (2)  cysts. 

NEOPLASMS.! 

A  neoplasm  is  a  morbid  growth  characterized  by  a  tendency  to 
persist  or  increase  in  size,  independently  of  changes  in  the  metabolism 
of  contiguous  or  s^^stemic  structures,  and  performing  no  useful  function. 
In  the  present  state  of  our  knowledge  the  most  striking  phenomenon 
in  connection  with  tumors  is  their  apparent  purposeless  existence;  the 
inflammatory  new  growths  result  from  the  reaction  of  the  tissues  to 
an  evident  cause,  and  are  characterized  by  efforts  to  overcome  the 
inciting  agent  or  protect  contiguous  tissues,  or  the  system  at  large, 
from  further  injury.  The  inflammations  and  infections  with  which  we 
are  familiar  are  attended  by  distinguishing  clinical  phenomena  and 
more  or  less  characteristic  anatomic  changes.  The  increased  tissue 
growth  seen  in  hypertrophy  supplies  structure  for  augmented  function 
upon  which  its  evolution  largely  depends  and  with  the  disappearance 
of  which  the  hypertrophy  tends  to  subside. 

The  general  tendency  to  regard  tumors  as  without  function  is  cor- 
rect in  part  only;  Waring-  states  that  renin  and  pepsin  may  be  ex- 
tracted from  the  cells  in  gastric  cancer,  and  that  from  both  the  primary 
and  secondary  growths  originating  in  the  pancreas,  ferments  normally 
developing  in  that  gland  may  be  found  in  varying  quantities.  In 
carcinoma  arising  from  epithelium  of  the  thyroid,  symptoms  of  hyper- 
thyroidism may  be  present,  disappearing  when  the  tumor  is  removed 
and  reappearing  with  recurrence  even  when  the  latter  is  metastatic. 
Albrecht^  describes  an  endothelioma  the  histology  of  which  indicated 
that  red  blood-cells  were  being  produced  within  the  tumor. 

General  Considerations. — For  purposes  of  clinical  description  and 
pathologic  study  certain  terms  are  used  in  connection  with  tumors 
with  which  the  student  should  be  familiar.  In  studying  tumors  for 
either  diagnostic  or  pathologic  purposes  there  should  always  be  a  definite 

'  For  clinical  study  of  tumors  the  works  of  Bland-Sutton,  and  Senn  are  espe- 
ciall}^  recommended.  An  exhaustive  clinical  and  pathologic  review  of  tumors 
is  given  by  Borst,  "Die  Lehre  v.  d.  Geschwulst.  m.  e.  mikroscop.  Atlas,"  Wies- 
baden, 1902.  See  also  Chantemesse  and  Podwyssotsky,  "  Les  Processus  Gen^raux," 
1905,  vol.  ii,  p.  61. 

^  "Jour,  of  Anatomy  and  Ph^'siolog^',"  London,  vol.  xxviii,  p.  140. 

^  "Miinch.  med.  Woch.,"  July  8,  1902. 

308 


TUMORS.  ^og 

routine  in  the  method  of  examination,  as  has  already  heen  insisted 
upon  when  ronsiderinjj  postmortems.  The  following  fjrder  is  com- 
mended: (i)  Describe  the  tumor;  (2)  its  relation  to  surrounding^  tr  u*- 
and  organs;  (3)  the  history  of  the  tumor;  (4)  the  history  of  the  ])aticiit. 
In  purely  clinical  studies  it  is  common  to  begin  with  the  history  c)f 
the  patient,  and  the  foregoing  order  may  be  reversed  without  affecting 
its  usefulness. 

1.  In  describing  the  tumor  the  following  points  may  be  of  aid  in 
diagnosis,  and  ought  to  be  developed  in  the  history:  (a)  Its  situation, 
superficial  or  deep,  on,  or  in  contact  with,  epithelial  surfaces,  deep  in 
a  purely  connective-tissue  area,  or  within  a  structure  composed  of  one 
or  both  tissues;  this  includes  the  organ  involved.  (6)  The  conjormatinu 
of  the  tumor:  Is  it  globular,  flat,  bossed,  pendulous,  pedunculated, 
pyriform,  conic,  excrescent,  polypoid,  dendritic,  sessile,  cauliflower, 
tuberous,  lobulated,  fungoid,  etc.?  (c)  The  size  of  a  tumor  may  be 
approximately  estimated  before  it  is  removed  from  the  body.  After 
removal  accurate  measurements  should  be  made  and  the  mass  should 
be  weighed,  {d)  Number:  Is  the  tumor  single — that  is,  solitary — or 
is  it  multiple?  If  multiple,  was  it  so  from  the  beginning,  or  was  one 
tumor  followed  by  a  succession  of  others?  Are  all  the  tumors  appar- 
ently alike,  having  the  same  conformation,  consistency,  and  similar 
location?  (<?)  Consistence:  Some  tumors  are  so  soft  that  they  fluctuate; 
others  are  semisolid,  gelatinoid,  solid,  hard,  or  even  churnated.  (f)  Color: 
This  includes  the  color  of  the  overlying  structures.  The  tissue  covering 
a  tumor  may  be  normal  or  inflamed;  it  may  contain  tortuous  veins; 
it  may  be  edematous,  or  even  pigmented;  it  may  be  so  vascular  that 
the  color  is  of  a  blood  tint,  either  pink  or  red,  or,  in  some  instances, 
cyanotic,  (g)  The  mobility  of  the  tumor:  Is  the  tumor  movable  in 
the  tissue  that  surrounds  it?  Is  it  movable  only  with  the  organ  in- 
volved, or  has  the  tumor,  as  well  as  the  affected  organ,  become  attached 
to  adjacent  structures?  (//)  Seiisibility:  Is  the  tumor  painful,  tender, 
sensitive  to  changes  in  temperature  or  to  atmospheric  conditions i"  Is 
the  pain  or  tenderness  constant,  remittent,  or  intermittent? 

2.  The  influence  of  the  tumor,  if  any,  upon  surrounding  structures: 
Are  they  involved,  inflamed,  edematous,  sensitive,  or  anesthetic? 

3.  The  history  of  the  gro'U'th:  How  long  has  the  tumor  persisted!'  Is 
it  growing  rapidly  or  slowly'  Has  its  growth  been  constant  or  inter- 
mittent? Is  its  g'rowth  influenced  by  any  of  the  functions  of  the  body' 
(For  example,  some  tumors  in  women  enlarge  during  menstruation.) 
What  pathologic  processes,  if  any,  are  i)rcscnt  within  the  tumor'  Is 
there  evidence  of  inflammation,  gangrene,  cyst  formation,  suppuration. 
infiltration,  or  of  degeneration? 

4.  History  of  the  patient.— Age:  Some  tumors  appear  m  the  y      • 
others  are  more  frequent  in  middle  life,  and  some  occur  in  th« 
Sex:  Some  tumors  are  more  frequent  in  the  male:  others,  in  the  f«  • 
Carcinoma  of  the  male  breast  occurs  in  about  one  per  cent,  of  '1' 

of  mammary  cancer.     Social  condition.   Married  or  single.     (' 
Certain  tuniors  have  long  been    recognized    as    frequentl" 
with  given  occupations:    r.  g..  chimney-sweep's  cancer.     // 
tumors  are  dependent,  apparently,— to  a  certain  extent,  at  ka-'.     ui»<>n 
given  habits:    e.  g.,  smokers'  cancer.     Heredity:    There  is  reason  to  be- 
lieve that  in  some  tumors  inheritance  may  play  a  part.     Has  the  general 


3IO  GENERAL  PATHOLOGY. 

nutrition  of  the  patient  been  influenced  in  any  way,  and  is  the  influence 
purely  mechanical,  such  as  may  result  from  the  weight  of  the  tumor, 
or  is  it  attributable  to  the  position?  Have  ulceration  or  infectious 
processes  modified  general  nutrition?  In  the  absence  of  any  other 
explanation,  it  may  be  inferred  that  the  tumor  itself  has  been  prejudicial 
to  the  patient's  health. 

Previous  history  of  the  organ  or  tissue  involved:  Is  there  a  history 
of  injury  or  inflammation,  such  as  might  occur  in  the  breast  during 
lactation?  Has  there  been  any  prcviotis  disease  of  the  gland  or  structure 
involved  f 

Causes} — It  is  not  improbable  that  different  tumors  arise  as  a  result 
of  the  action  of  various  causes.  As,  however,  we  know  very  little 
concerning  the  exact  etiology  of  any  particular  tumor,  certain  general 
considerations  are  permissible.  The  older  theories,  attributing  the 
occurrence  of  tumors  to  alterations  in  the  humors  of  the  body,  par- 
ticularly of  the  blood,  and  similar  hypotheses,  may  at  once  be  dis- 
carded.    The  following  hypotheses  are  deserving  of  consideration: 

I.  The  Durante-Cohnheim  Inclusion  Theory.^ — This  theory  is  based 
upon  the  supposition  that,  during  embryonic  development  and  the 
specialization  of  the  cells  entering  into  the  formation  of  organs  and 
adult  tissues,  more  embryonic  elements  are  produced  than  are  necessary, 
and  that  these  cellular  elements  become  quiescent  in  the  tissues,  where 
they  may  remain,  constituting  embryonic  "rests"  or  "remnants,"  from 

'  The  scope  of  this  work  does  not  permit  the  introduction  of  exhaustive  refer- 
ences. Those  interested  in  the  literature  bearing  on  the  etiology  of  tumors  may 
find  or  can  trace  the  most  important  communications  from  the  references  which 
follow.  I  have  purposely  divided  them  into  two  groups.  Articles  supporting 
the  parasitic  origin  of  neoplasms:  Bosc,  "La  Presse  Med.,"  Jan.  14,  1903,  p.  53. 
Schiiller,  "  Parasitare  Krebsforschung  und  der  Nachweis  der  Krebsparasiten  am 
Lebenden."  Abhandlungen  aus  dem  Gebeiten  der  Krebsforschung  und  verwand- 
ten  Gebieten,  1903,  Heft  i,  Berlin;  also  "Centralbl  f.  Bakt.,"  Dec.  12,  1904,  p. 
547.  Homus,  These  de  Paris,  1905.  Sanfelice,  "  Rif orm  med.,"  Sept.  6,  1904; 
also  "Wien.  med.  Presse,"  1904,  No.  42.  Plimmer,  "Jour.  Path,  and  Bact.,"  1S94, 
vol.  ii,  p.  486.  Podwyssotsky,  "Zeit.  f.  klin.  Med.,"  vol.  47,  Nos.  3  and  4.  Fein- 
berg,  "Wien.  klin.  Woch.,"  1903,  Nov.  5,  p.  1236,  and  Nov.  12,  p.  1272.  Gaylord 
(and  others).  Fourth  Ann.  Report,  Cancer  Lab.  of  the  N.  Y.  State  Board  of  Health, 
1902-03.  Robertson  and  Wade,  "Lancet,"  Jan.  28,  1905.  Monsarrat,  "The 
Hospital,"  Jan.  30,  1904.  Roger  and  Weil,  "Arch,  de  Med.  Exp.  et  Anat.  Path.," 
March,  1904,  p.  145.      Leyden,  "Deut.  med.  Woch.,"  May  S,  1902. 

Articles  attributing  neoplasms  to  causes  other  than  parasites:  Farmer,  "  Moore 
and  Walker,"  Royal  Soc,  Dec.  10,  1903.  Foulerton,  "The  Practitioner,"  July 
and  August,  1902.  Futterer,  "Medicine,"  March,  1902.  Senn,  "Med.  Record," 
July  13,  1901.  Lubarsch,  "  Patholog.  Anat.  u.  Krebsforschung,"  1902.  Rogers, 
"Annals  of  Surgery,"  Aug.,  1903,  p.  280.  Bashford  and  Murray,  "Lancet,"  Feb. 
13,  1904,  p.  413.  Honda,  "Virchow's  Arch.,"  clxxiv,  Oct.,  1903,  p.  96.  Hew- 
lett, "Jour,  of  State  Medicine,"  Nov.,  1904.  Morris,  "Lancet,"  Dec.  12,  1903,  p. 
1634.  Hertwig,  Festschrift  zur  von  Geburtstage  von  E.  Hseckel,  1904,  p.  303. 
Richardson,  "N.  Y.  Med.  Jour.,"  Aug.  27,  1905,  p.  389,  very  full  bibliography. 
Cohn,  "Zeit.  f.  klin.  Med.,"  vol.  56,  Nos.  i  and  2.  Beard,  "Lancet,"  Feb.  11, 
1905,  p.  385.  Orth,  "Ann.  of  Surg.,"  1904,  xi,  No.  6,  p.  733.  Greenough,  "Jour, 
of  Med.  Research,"  Jan.,  1905,  p.  137.  Nichols,  "Jour,  of  Med.  Research,"  Jan., 
1905,  p.  187.  Adami,  "The  Medical  Chronicle,"  June,  1900,  also  "Yale  Med. 
Jour.,"  March,  1901.  Baldwin,  "The  Physician  and  Surgeon,"  Feb.,  1903,  p.  49- 
Griinbaum,  "Brit.  Med.  Jour.,"  Dec.  17,  1904,  p.  1634.  Israel,  "Arch.  f.  klin. 
Chir.,"    1902,   vol.   67,   No.   3. 

^  Monti  ("Fundamental  Data  of  Modem  Pathology,"  Sydenham  Translation, 
p.  51)  has  shown  that  Durante  enunciated  this  theory  in  all  its  essential  details 
before  the  appearance  of  Cohnheim's  publication. 


TUMDRS.  ^1  I 

which,  later,  tuniur  Rtrniati'tn  takes  phicc.  i'.ariuriii  sJidwimi  uuil  H 
was  i)Ossil)le  for  experimentally  (lis])lare(l  j^eniiinai  layers  to  develop 
in  a  new  condition,  and  Zahn,  followed  by  Le<jpold,  jjroved  that  fetal 
tissues,  especiallv  cartilage,  withstootl  transplantatKjn  far  better  than 
fully  developed  structures.  Roux  demonstrated  the  structural  exist- 
ence of  the  hypothetic  bodies  from  which  Cohnheim  thought  tumors 
arose.  Such  embryonic  rests  or  remnants  would  he  exceedingly  likely 
to  occur  where  developmental  processes  are  complex,  as,  for  example, 
where  different  forms  of  epithelium  join.  Such  |)oints  of  tumor  election 
undoubtedlv  occur,  as  is-  shown  by  the  development  of  cancer  at  the 
various  orifices  of  the  body  and  at  ])oints  of  epithelial  transition,  such  as 
the  lip.  cervix  uteri,  etc.  This  theory  also  explains  to  advantage  the 
occurrence  of  chondroid  tumors  in  or  from  bone,  and  of  melanotic  sarco- 
mata from  quiescent  pigmented  cells  in  moles,  and  affords  a  most  accept- 
able explanation  for  the  development  of  dermoid  cysts.  The  theory, 
however,  is  wanting  in  several  ways.  In  the  first  place,  admitting  the 
occurrence  of  these  remnants,  it  would  appear  that  a  further  etiologic 
factor  is  necessarv  in  order  to  stimulate  them  to  renewed  activity. 
Another  objection  is  afforded  by  the  fact  that  many  localities  in  which 
complex  developmental  processes  occur,  such  as  the  heart  and  the  ner- 
vous system,  are  singularly  free  from  tumors,  and  that  when  they  do 
occur  in  such  tissues,  they  are  not  commonly  situated  at  points  at  which 
the  complexity  of  development  is  most  marked.  Epithelial  rests  are 
sometimes  demonstrable,  and  yet  no  tumor  formation  occurs.  The 
occurrence  of  tumors  as  the  result  of  trauma  (to  be  considered  later)  is 
inconsistent  with  this  theory. 

2.  Injury  and  inflammation  appear  to  be.  in  a  certain  percentage 
of  tumors,  important  etiologic  factors.  Persistent  or  long-continued 
irritation  seems  to  favor  the  development  of  tumors  belonging  to  the 
epithelial  group.  As  examples  of  such  tumors  the  following  may  be 
mentioned:  Carcinoma  of  the  scrotum  in  chimney-sweeps;  epithelioma 
of  the  arm  in  workers  with  paratlin  and  tar;  smokers'  cancer  of  the  lip  or 
tongue  and  cancer  of  the  tongue  apparently  due  to  injury  by  a  carious 
tooth;  and  epithelioma  orginating  in  the  margins  of  chronic  ulcerative 
processes.  Among  the  nonmalignant  epithelial  tumors  the  develop- 
ment of  which  appears  to  be  favored  by  injury  or  irritation  may  be 
cited  the  papillomatous  masses  due  to  the  accumulations  of  irritating 
discharges,  particularly  around  the  anus  and  external  genital  organs, 
when  the  parts  are  riot  kept  properly  cleansed.  Sarcoma  following 
fracture  or  injurv  of  bone,  and  tibroneuromata  of  the  severed  ends  of 
nerves  after  amputation,  may  be  mentioned  as  connective-tissue  tumors 
offering  strong  support  to  this  theory.  The  occurrence  of  tumors  at 
points  particularly  liable  to  injury  is  another  argument  in  its  favor. 

Numerous  objections  have  been  made  to  the  acceptance  of  this 
theory.  In  about  eighty-five  per  cent,  of  all  tumors  no  histor>-  of  in 
jun.-  can  be  obtained.  'On  the  other  hand,  the  frequency  with  which 
injuries  are  received  is  not  at  all  in  proportion  to  the  total  number  of 
tumors  occurring.  Parts  particularly  subject  to  injurv,  such  as  the 
hands  and  feet,  are  not  commonly  affected,  and  the  nipple,  which  is 
frequentlv  injured,  is  rarely  the  seat  of  a  tumor. 

J.  Pii'msiiic  Influence. — The  germ  theor>-  has  been   invoked  to  ex- 
plain the  formation  of  tumors,  particularly  the  malignant  neoplasms,  in 


312  GENERAL  PATHOLOGY. 

which  metastases  are  conspicuous.  By  some  the  essential  parasitic  bodv 
is  beheved  to  be  an  animal  parasite  belonging  to  the  protozoa  and  resem- 
bling, if  not  identical  with,  the  coccidia  already  described.  (See  p.  184.) 
Others  believe  that  the  infecting  body  is  a  vegetable  organism  belonging 
to  the  blastomycetes.  In  further  support  of  the  parasitic  origin  of 
tumors  the  demonstrable  autoinoculability  of  cancer  is  adduced.^  Thus, 
it  has  been  shown  that  cancer  of  one  labium  may  attack  the  point  of  con- 
tact upon  the  opposite  labium ;  cancer  of  the  cervix  may  attack  the  con- 
tiguous vaginal  vault;  and  cancer  reaching  the  peritoneal  surface  may 
show  a  similar  inoculability.  It  may  be  said  at  this  point  that  such  in- 
oculability  may  be  an  evidence  of  grafting,  just  as  epithelial  cells  may  be 
grafted  from  place  to  place,  or  from  one  individual  to  another — skin 
grafting — without  of  necessity  invoking  the  intervention  of  any  parasite. 
A  similar  explanation  is  offered  with  regard  to  the  grafting  of  cancer 
from  one  animal  to  another.  The  inoculation  of  tumors  thought  to  be 
sarcomata,  and  occurring  on  the  genitalia  of  dogs,  is  believed  by  some 
to  be  an  evidence  of  the  inoculability  of  sarcomata.  Others  maintain 
that  the  tumor  in  question  is  not  a  sarcoma,  but  that  it  belongs  to  that 
group  of  inflammatory  embryonic  cellular  collections  not  easily  differen- 
tiated from  round-cell  sarcoma. 

4.  Parasitistn  of  Cells. — It  is  not  impossible  that  normal  cellular 
elements  may  take  on  a  certain  parasite-like  property  that,  in  the  presence 
of  reduced  resistance  afforded  by  other  elements,  permits  of  their  exten- 
sion beyond  normal  limits.  Thus,  in  cancer  cellular  elements  that  we 
believe  to  be  of  epithelial  origin  are  found  abundantly  infiltrating  con- 
nective tissues.  Normally,  epithelium  does  not  so  extend,  nor,  in  most 
instances,  even  when  introduced  experimentally,  does  it  acquire  any  such 
property.  Should  further  experiment  show  that  conditions  may  arise 
under  which  epithelium  can  acquire  or  manifest  the  faculty  of  intracon- 
nective-tissue  growth,  without  the  intervention  of  any  other  factor,  we 
may  assume  that  the  manifestation  of  this  parasite-like  character  leads 
to  the  development  of  cancer. 

5.  Adami  presents  a  most  fascinating  argument  in  favor  of  his  view 
that  whatever  may  be  the  origin  of  tumors,  the  most  important  element 
in  their  production  is  the  fact  that  the  cells  forming  the  neoplasm  give 
up  the  habit  of  function  and  acquire  the  habit  of  growth.  Reproduction 
is  of  course  an  essential  function  in  all  cells,  but  in  addition  to  pro- 
liferative power  every  cell  is  endowed  with  the  inherent  capacity  to 
perform  some  specific  duty,  in  the  consummation  of  which  it  utilizes 
more  or  less  of  the  energy  that  it  is  able  to  transform  from  the  nutrition 
supplied.  If  the  cell  ceases  to  perform  this  specific  function,  what- 
ever that  duty  may  be,  the  energy  previously  converted  in  that  direction 
is  now  transferred  to  the  reproductive  capacity  of  the  cells,  thereby  lead- 
ing to  proliferation  in  excess  of  the  normal.  The  originator  of  this  sug- 
gestive hypothesis  fully  recognizes  the  necessity  for  some  reason  account- 
ing for  the  cell's  acquisition  of  the  habit  of  growth  at  the  expense  of  the 
habit  of  function.  The  fact  that  malignant  neoplasms  of  epithelial 
origin,  and  particularly  those  arising  from  the  mammary  gland  and 
uterus,  appear  at  a  time  when  function  is  on  the  decline,  is  fully  in  sup- 

^  See  Loeb,  "Jour,  of  Med.  Research,"  vol.  viii,  June,  1902,  p.  44;  "Virchow's 
Arch.,"  1903,  Bd.  172:  "Amer.  Med.,"  March  14,  1903,  vol.  v,  p.  412.  Dagonet 
and  Auclaire,  "Arch,  de  Med.  Exp.,"  Sept.,  1904,  p.  552. 


TUMORS.  313 

port  of  Adami's  view.  He  further  maintains  that  irritation,  parasitic 
or  otherwise,  may  so  modify  the  cell  that  proliferation  becomes  excessive 
and  secretion  or  other  specific  function  proi)ortionately  diminishes. 

6.  Predisposing  Causes. — The  foregoing  brief  consideration  of  the 
most  plausible  reasons  advanced  to  explain  neoplastic  growths  mdicates 
our  ignorance  of  the  essential  etiologic  factor  in  tumor  formation. 
There  are,  however,  certain  predisposing  elements  worthy  of  considera- 
tion. Some  of  the  conditions  previously  considered  may  be  active  only 
in  this  way.  Trauma  and  inflammation  may  predispose  to  tumor 
fonnation,  just  as  they  predispose  to  infection,  and  long-continued 
irritation  or  prolonged  ulceration  may  act  only  as  jjredisposing 
elements.  With  regard  to  age,  it  may  be  said,  in  a  general  way,  that 
physiologic  activity  favors  the  development  of  sarcoma,  while  senes- 
cence, or  physiologic  decline,  predisposes  to  the  occurrence  of  cancer 
(Da  Costa).  The  influence  of  inheritance  can  not  be  entirely  ignored, 
although  it  is  probably  slight. 

Xe()])lasms  are  subject  to  two  general  laws: 

1.  Miiller's  Law. —  The  tissue  that  forms  the  tumor  has  its  type  in  a 
tissue  of  the  organism,  cither  adult  or  embryonic .  By  this  is  meant  that, 
no  matter  what  the  cellular  elements  of  a  tumor  may  be,  such  elements 
occur  as  normal  structures  in  the  adult  tissues  or  in  the  tissues  of  the 
embryo  at  some  period  of  its  development. 

2.  Virchow's  Law. —  The  cellular  elements  of  a  tumor  are  derived 
from  the  pre-existing  cells  of  the  organism.  Virchow  adds  that  they  are 
the  progeny  of  the  cells  of  the  connective  tissue — a  view  clearly  incorrect 
with  regard  to  many  neoplasms. 

By  the  acceptance  of  these  two  laws  we  arrive  at  the  fact  that 
tumors  spring  from  structures  once  normal,  and  represent,  when  fully 
developed,  tissues  that  were  normal;  in  other  words,  tumors  are  not 
importations  into  our  bodies,  but,  like  all  other  morbid  processes,  are 
per\'ersions  of  normal  cellular  activity. 

Tumors,  in  a  general  way,  obey  the  laws  that  regulate  normal  struc- 
tures, yet  to  some  extent  they  live  independently  of  the  surrounding 
tissue.  They  usually  possess  their  own  circulation,  and  disseminate  and 
proliferate  at  the  expense  of  the  adjacent  tissue.  While  the  patient 
may  show  every  evidence  of  failing  nutrition,  and  the  adult  and  fully 
formed  tissues  of  the  body  are  undergoing  progressive  wasting,  the 
tumor  cells  may  not  lessen  in  the  least  the  rapidity  of  their  growth. 

Tumors  are  said  to  enlarge  or  to  extend  either  by  (a)  interstitial 
growth  or  by  (6)  dissemination.  By  the  former  is  meant  that  tlu-  growtli 
within  the  tumor  is  uniform;  that  it  increases  in  size  by  proliferation 
of  its  cells,  without  any  dislodgment  except  that  incident  to  one  cell 
pressing  upon  and  altering  the  position  of  another  during  the  process 
of  multiplication.  Such  tumors  are  likely  to  form  capsules,  the  capsule 
developing  either  as  a  part  of  the  tumor  or  by  condensation  of  the  sur- 
rounding tissue.  The  simple  nonmalignant  tumors  may  have  capsules 
formed  in  either  of  the  two  ways  indicated,  but  the  malignant  neo- 
plasms are  less  likely  to  have  anything  like  a  capsule,  by  reason  of  the 
fact  that  thev  grow  largely  by  dissemination. 

(b)  Growth  by  dissemination  is  said  to  be — (i)  growth  by  infiltration; 
(2)  growth  by  metastasis. 

I.  Local   dissemination  <>r  infiltration  is  an  extension  of   the  tumor 


314 


GENERAL  PATHOLOGY. 


into  the  surrounding  tissue;  this  usually  occurs  by  the  entrance  of  the 
tumor  cells  into  the  lymph-spaces.  Tumors  growing  by  infiltration 
possess  no  sharply  defined  border,  and  are,  therefore,  without  capsules, 
thus  rendering  the  surgeon  unable  to  determine  definitely  how  far  from 
the  neoplasm  it  is  necessary  to  keep  in  order  to  remove  all  of  the  tumor 
tissue. 

2.  Metastasis. — When,  as  just  indicated,  the  tumor  cells  penetrate 
the  primitive  lymph-spaces,  it  will  be  seen  how  easy  it  is  for  such  in- 
filtrated cells  to  be  caught  in  the  lymph-stream  and  carried  to  the  lymph- 
nodes  into  which  the  lymphatics  of  the  area  involved  empty;  such  ex- 
tension is  most  common  in  cancers,  although  it  may  occur  in  sarcoma, 
and  is  known  as  metastasis  by  the  lymph-stream. 

Extension  of  neoplasms  by  the  lymphatics  should,  and  ordinarily 
does,   include  metastasis  by   the  lacteals.     The  latter  is  of  infrequent 

occurrence,  but  when  present  gives  rise 
to  appearances  that  may  mislead  the  un- 
initiated. The  lacteal  vessels  of  the  in- 
testinal wall  and  mesentery  become 
tortuous,  cord-like,  and  irregularly  en- 
larged, sometimes  presenting  a  monili- 
form  aspect.  In  some  cases  the  con- 
dition is  associated  with  a  chylous 
transudate  in  the  peritoneal  cavity; 
often  there  is  no  such  evidence  of  ob- 
struction. Usually  emaciation  or  other 
evidence  of  malnutrition  is  extreme  and 
unaccounted  for  by  the  character  or 
extent  of  the  growth. 

Tufifier^  calls  attention  to  cutaneous 
inoculation  from  ulcerating  surface  can- 
cers. He  believes  that  the  small  out- 
Iving  nodules  often  adjacent  to  car- 
cinoma of  the  breast  are  due  to  trans- 
cutaneous autoinoculation.  I  have  seen 
a  few  instances  of  this  type  of  neoplastic 
extension.  It  is  well  known  that  when 
an  ulcerating  malignant  tumor  is  con- 
stantly in  contact  with  a  previously 
healthv  surface  the  tissues  of  the  latter  may  be  invaded  by  the  growth. 
In  this'  way  a  neoplasm  of  the  alveolar  process  may  reach  the  mucosa  of 
the  cheek  or  tongue,  a  cancer  of  the  cervix  invade  the  vaginal  vault, 
or  a  malignant  tumor  of  one  labium  inoculate  the  apposed  surface  of 
the  vulva  or  thigh. 

Metastasis  by  the  Blood. — In  certain  tumors,  particularly  in  sarco- 
mata, the  walls  of  the  blood-vessels  are  poorly  formed — indeed,  nothing 
structurally  comparable  to  the  normal  wall  may  be  demonstrable;  the 
blood  traversing  such  timiors  passes  through  what  may  be  called  sluice- 
ways, the  walls  of  which  are  not  uncommonly  formed  entirely  of  tumor 
cells.  These  cells  may  drop  off  into  the  blood-stream  and  be  carried 
along  as  emboH  (neoplastic  emboli),  reproducing  the  tumor  wherever 
thev  lodge.  Again,  a  tumor  may  infiltrate  the  wall  of  the  blood-vessel 
'  "La  Bull,  m^d.,"  Dec.  3,  1904. 


Fig.  i6s- — Small  Intestine. 
Dilatation  of  the  lacteals  due  to  sarcomatous 
implication  of  the  receptaculum  and  adja- 
cent tissues.  The  primary  growth  in  this 
case  was  thought  to  have  been  in  the 
adrenal.     (Dra^^^ng  i  natural  size.) 


TUMORS.  315 

and  project  into  its  interior,  and  small  fraj^ments,  breaking  oil,  may 
be  carried  to  distant  parts.  The  walls  of  the  veins  bein^  thinner  than 
those  of  the  arteries,  infiltration  is  rendered  easier,  and  the  circulatory 
conditions  make  the  consequences  more  disastrous.  Neoplastic  emboli 
formed  bv  penetration  of  the  femoral  artery  can  be  carried  only  to  the 
structures  of  that  limb;  if,  however,  the  emboli  be  thrown  into  the 
femoral  vein,  their  next  point  of  lodgment  would  probably  be  the  lung. 

Pigmentation  occurring;  in  tumors  may  result  from  hemorrhage  within 
the  lunior  and  from  the  disintei^ration  of  blood  colorinj^'-matter,  or  it 
may  be  due  to  the  fact  that  the  neoplastic  cells  ])roducc  a  pigment, 
such  as  is  seen  in  the  chloroma,  melanotic  sarcoma,  and  a  few  other 
tumors.  It  may  also  be  due  to  the  development  of  certain  bacteria, 
particularly  if  the  tumor  be  ulcerated. 

Classification. — Clinically,  tumors  are  said  to  be  (a)  benign  or  (b) 
malignant.  By  the  former  is  meant  that  the  tumor  of  itself  does  not 
neccssarilv  involve  danger  to  life,  while  the  latter  implies  that,  if  un- 
disturbed, the  neoplasm  will  eventually  prove  fatal.  A  tumor  ordi- 
narilv  innocent  or  benign  may  destroy  life  simply  by  its  location;  for 
exam]^le,  a  fibrous  tumor  growing  on  the  inside  of  the  skull.  This, 
however,  does  not  justify  our  placing  fibrous  tumors  with  the  malignant 
neoplasms,  as  the  fact  that  it  proves  fatal,  in  the  particular  instance 
cited,  is  what  Park  has  termed  "malignancy  by  accident  of  location." 
In  this  connection  it  is  well  to  recall  that  benignancy  and  malignancy 
are  relative  qualities,  and  that  sometimes  a  neoplasm,  possessing  the 
clinical  and  pathologic  attributes  that  are  practically  always  accom- 
panied by  malignancy,  may  astonish  the  observer  by  rapidly  disappear- 
ing. Cathcart*  has  collated  numerous  instances  going  to  show  that  the 
usually  sharply  drawn  line  between  innocent  and  malignant  tumors 
is  not  alwavs  justified  by  clinic  and  pathologic  data.  Osier  reported 
a  number  of  cases  of  clearly  established  cancer  in  which,  although 
recurrence  followed  operation,  the  tumor  finally  disappeared.  This 
so-called  spontaneous  cure  of  malignant  tumors  is  so  infrequent  that 
clinicians  commonly  ignore  its  occurrence.  The  conversion  ot  non- 
malignant  into  malignant  tumors  is  much  more  frequent;  fibromata  and 
mvomata  are  sometimes  transformed  into  sarcomas,  and  adenoma  and 
papilloma  into  cancer. 

At  one  time  it  was  quite  the  custom  for  clinicians  to  classify  tumors 
according  to  some  symptom  or  peculiarity  of  shape.  As  examples  of 
this  may  be  mentioned,  scirrhus,  for  hard,  and  encephaloid,  for  soft 
cancer;  again,  bleeding  tumors,  when  fungoid,  all  came  under  the  one 
head,  "fungus  hematodes."  No  fully  satisfactory  classification  of 
tumors  can  be  made  at  present;  when  we  become  familiar  with  their 
etiology,  it  is  probable  that  more  may  be  accomjilished.  The  exten- 
sion of  our  knowledge  as  to  the  minute  structure  of  tumors  has  led  to 
a  classification  based  upon  their  morbid  histology  and  histogenesis. 
Even  if  possessing  no  other  advantages  this  basis  offers  a  method  by 
which  neoplasms  may  be  brought  into  related  groups,  thereby  facili- 
tating clinical   and   patholoi^nr  studv. 

Classification  Based  on  Histogenesis. — Granting  the  correctness  of 
the  law  of  MuUer,  a  tentative  classification  is  possible,  based  upon  the 
resemblance  of  tumors  to  the  normal  tissues,  either  adult  or  embryonic. 
'  "Brit.  Med.  Jour,"  June  4,  1904.  V-  ^3°°- 


3i6 


GENERAL  PATHOLOGY. 


All  tissues  spring  from  one  of  two  types:  (/)  Epithelium;  (2)  connective 
tissue.  Tracing  these  back  to  the  blastodermic  layers,  they  are  de- 
veloped as  follows: 

(7)  Epithelium,  from  the  epiblastic  and  hypoblastic  layers  (or  outer 
and  inner  layers)  of  the  blastoderm.  (2)  Connective  tissue,  from  the 
mesoblast  (or  middle  layer)  of  the  blastoderm.  All  neoplasms  spring 
from  one  of  these  two  types,  each  type  of  tissue  having  two  varieties: 

(i)  Epithelium:  (a)  Adtdt  or  typical;  (b)  embryonic  or  atypical. 
(2)  Connective  tissue  :  (a)  Adtdt  or  typical;  (b)  embryonic  or  atypical. 

Adtdt  or  typical  tumors  are  those  having  their  type  in  the  adult 
body;  clinically,  these  are  benign. 

Em.bryonic  or  atypical  tumors  are  composed  of  cellular  elements 
resembling  those  found  in  the  embryo  at  some  stage  of  its  develop- 
ment; clinically,  such  tumors  are  malignant. 


EPITHELIAL  TUMORS. 

Adult  Epithelial  Tumors. 

I.  Papilloma. — These  growths  are  formed  from  cutaneous  and  mu- 
cous papillae,  and  consist  of  a  fibrous  stroma,  or  stem,  containing  blood- 
vessels and  lymphatics,  and  possessing  an  epithelial  investment.  The 
epithelium  is  of  the  kind  normal  in  the  particular  situation  in  which 
the  growth  is  located.  The  histologic  structure  of  a  papilloma  resembles 
that  of  the  ordinary  papilla,  and  consists  of  a  basis  of  connective  tissue, 
richly  cellular,  from  which  project  toward  the  surface  numerous  papil- 
lary processes,  each  process  supporting  blood-vessels  that  end  in  a  capil- 
larv  loop,  the  whole  being  enveloped  in  a  covering  of  epithelium.  Tu- 
mors of  this  class  are  commonly  the  product  of 
chronic  irritation,  particularly  when  the  latter  is 
associated  with  a  low-grade  inflammatory  pro- 
cess. Irritating  discharges,  especially  from  the 
genital  and  anal  borders,  may  lead  to  the  de- 
velopment of  warts.  A  jagged  tooth,  by  con- 
stantly subjecting  the  mucosa  to  injury,  may 
give  rise  to  papillomas  of  the  tongue  or  cheek. 
The  papillae  vary  in  length:  in  the  ordinary 
wart  they  are  short;  in  the  villous  papilloma 
they  appear  as  long,  delicate  fibrils,  giving  off 
secondarv  and  tertiary  shoots.  On  the  skin  the 
epithelial  covering  is  thick,  hard,  and  stratified, 
and  actually  binds  the  papillae  into  a  solid 
mass ;  on  mucous  membranes  the  slender  vascular  processes  are  covered 
with  very  delicate  and  easily  lacerated  epithelium. 

Site. — Papilloma  may  appear  anywhere  on  the  skin  or  mucous  mem- 
brane; as  a  rule,  they  grow  from,  and  closely  imitate,  pre-existing 
papillae.  They  rarely  occur  where  no  papillae  exist;  in  such  rare  cases 
the  connective-tissue  core  springs  directly  from  the  subepithelial  con- 
nective tissue — this  is  the  case  in  the  stomach  and  larynx. 

Clinical  Characters. — Clinically,  warts  are  benign,  or  innocent. 
They  may  occur  at  any  age ;  may  be  single  or  multiple ;  may  disappear 
without  any  operative  interference :  this  is  especially  true  of  multiple 


Fig.    165.  —  Papilloma 
{Gould.) 


TUMORS. 


.S'7 


warts.  When  occurring  on  mucous  surfaces,  they  are  highly  vascular, 
and,  owing  to  their  thin  epithelial  covering  and  delicate  connective- 
tissue  matrix,  are  easily  torn,  sometimes  giving  rise  to  fatal  hemorrhage. 
This  is  especially  true  of  papilloma  of  the  bladder  and  similar  growths 
occurring  in  the  urethral  orifice.  In  the  young,  warts  are  occasion- 
ally transformed  into  sarcomata;  in  advanced  life  warts  and  warty 
surfaces  (ichthyosis  linguie)  may  be  converted  into  cancer. 

Varieties. — (i)  Skin    ivarts:  (2)  villous   warts;  (3)  intracystic   warts. 

1.  Skin  Warts. — (See  Fig.  165.)  Skin  warts  are  overgrown  papilla*, 
and  on  section  the  epithelium  will  be  found  to  pass  from  one  papilla  to 
another  in  an  unbroken  line  without  invading  the  fibrous  framework. 
They  vary  in  size,  and  may  become  mottled  with  black  pigment  (melan- 
otic). Cutaneous  warts  may  be  single  or  multiple,  and  may  disappear  in 
one  area  and  appear  in  another,  thus  leading  the  laity  to  believe  them 
migratory.  Ordinarily,  the  cutaneous  papilloma  appears  as  a  hard, 
abruptly  elevated  mass,  ap- 
parently of  epithelium,  pre- 
senting an  irregular  or 
"  warty  "  surface,  usually 
divided  by  deep  fissures.  On 
section,  the  relation  between 
the  stroma  and  the  epith- 
elium may  be  seen  even  with 
the  naked  eve. 

2.  Villous  Warts.— These 
commonly  spring  from  the 
mucous  membrane,  usually 
of  the  bladder,  and  occa- 
sionally of  the  renal  pelvis; 
the  condition  is  termed  villous 
disease.  The  general  appear- 
ance of  the  long,  branching, 
feathery  tufts  resembles  that 
of  the  delicate  chorionic  villi ; 
structurally,  the  villi  consist 
of  a  connective-tissue  core 
traversed  by  delicate  blood- 
vessels, the  whole  being  sur- 
mounted by  epithelium.  They  may  be  sint^lc  or  multiple,  sessile  or 
pedunculated.  The  detachment  of  small  vilU  may  occasion  hemor- 
rhage, which,  with  frequent  recurrence,  gives  rise  to  profound  anemia. 
The  size  of  the  villous  mass  often  bears  no  relation  to  the  severity  of  the 
hemorrhage;  the  writer  has  examined,  at  autopsy,  a  fatal  case  in  which 
the  papilloma  was  not  larger  than  a  gram  of  wheat.  The  detachment  of 
villi  is  usually  brought  about  by  their  being  forced,  during  the  last  stage 
of  urination.'into  the  urethra,  where  hmbric-c  are  caught;  distention  of 
the  bladder  pulls  upon  the  incarcerated  projections,  breaking  them  off. 
and  thereby  inducing  hemorrhage.  Carcinomatous  transformation  ot 
vesical  pa])illoma  occurs. 

3.  Intracystic  Warts.— These  may  occur  within  almost  any  cyst 
cavity  lined  by  epithelium,  more  especially  those  cysts  developing  in 
glands:  e.  (;.,  mammary,  thyroid,  and  ovarian  cysts.     In  cysts  formed 


a  b    ^" 

I'lC.    166.— Papilloma  with  Tendency   towakd    VilloI's 

Formation. — (Schmaus.) 
II.  Connective-tissue  basis  containing  numerous  blood-ves-sels. 

ft,    b.    Epithelial  coverinR. 


3l8  GEXERAL  PATHOLOGY. 

in  the  mammary  gland,  particularly  in  those  cysts  arising  during  the 
gro^wiih  of  fibrous  tumors  of  the  breast,  the  wall  may  be  lined  by  a  papil- 
lomatous outgrowth.  Tumors  composed  of  papillomatous  masses  in 
the  interior  of  dilated  galactophorous  ducts  or  mammary  acini  are  spoken 
of  as  intracaiialicnlar  papilloiuata.  Sometimes  the  C3^st  is  said  to  be 
papillomatous.  In  many  instances  it  is  quite  impossible  to  determine 
whether  the  cyst  preceded  the  papillary  growth  or  whether  the  reverse 
was  the  case.  Examination  of  a  number  of  such  cysts  usually  shows 
that  the  papilloma  is  evidently  a  secondary  process.  Occasionally,  the 
cyst  may  be  distended  with  the  papillary  masses,  the  fluid,  probably 
present  at  some  time,  having  entirely  disappeared.  Cysts  containing 
such  papillomatous  masses  are  sometimes  seen  in  the  liver.  The  villous 
outgrowth  resembles  that  of  villous  papilloma,  and  the  epithelial  cover- 
ing is  usually  the  same  as  that  of  the  cyst  wall;  it  may  be  cylindric,  tall 
or  flat,  and  even  ciliated.  The  size  of  such  masses  varies  within  wide 
limits,  and  the  fact  that  their  presence  is  at  times  unsuspected  would 
lead  one  to  regard  them  as  sources  of  no  danger.  Occasionally,  how- 
ever, scirrhus  of  the  breast  follows  or  is  associated  with  this  form  of 
papillary  disease. 

II.  Adenoma. — An  adenoma  is  a  tumor  constructed  upon  the  type 
of  a  gland.  Adenomata  are  of  slow  growth,  and  are  believed  to  have 
their  origin  in  some  quiescent,  congenitally  displaced  rudiment;  their 
ducts  do  not  communicate  with  the  normal  gland  nor  do  their  acini 
elaborate  a  secretion;  they  are,  as  a  rule,  completely  encapsulated,  thus 
distinguishing  them  from  localized  hypertrophies.  Clinically,  they  are 
benign.  The  secondary  changes  to  which  they  are  liable  are  fatty 
degeneration  of  the  epithelium,  dilatation  of  the  saccules  and  tubules 
into  cvsts,  and  mucoid  softening.  As  adenomata  contain  both  connective- 
tissue  and  epithelial  cells,  transformation  into  sarcoma  and  into  car- 
cinoma is  possible;  the  former  is  more  frequent  in  the  young,  and  the 
latter  in  the  aged. 

Site. — They  may  develop  in  any  glandular  structure  or  in  any  tissue 
containing  glandular  structure.  The  chief  species  of  adenoma  are :  Mam- 
mary, sebaceous,  thyroid,  prostatic,  parotid,  hepatic,  renal,  ovarian, 
testicular,  gastric,  Fallopian,  and  uterine.  The  important  varieties  of 
the  tumor  are  the  (i)  Acinr^is;  (2)   tubular. 

1.  Acinous  Adenoma. — This  variety  consists  of  numerous  saccules 
or  acini  lined  with  small  epithelial  cells,  which  are  often  two  or  three 
layers  deep.  The  acini  communicate  with  one  another  and  are  grouped 
together,  being  separated  by  a  connective-tissue  matrix  in  which  are 
situated  the  blood-vessels.  The  connective-tissue  or  fibrous  stroma  varies 
in  amount.  Adenoma  of  the  breast  is  generally  seen  in  young  girls  at 
about  the  age  of  puberty.  The  tumor  is  usually  bossed  or  lobulated, 
irregular  in  conformation,  and  encapsulated.  Acinous  adenoma  is  rare, 
but  two  cases  having  come  under  the  author's  observation  among  the 
hundreds  of  tumors  sent  to  the  laboratory.  Fibromata  containing  more 
or  less  glandular  structure  are  not  uncommon,  and  are  called  fibroadeno- 
mata.  It  is  often  quite  impossible  to  determine  whether  the  gland 
structure  present  is  newly  formed  or  merely  normal  breast  tissue  which 
has  been  incorporated  in  the  fibroma. 

2.  Tubular  Adenoma. — This  variety  is  very  common  in  mucous 
membranes  possessing  tubular  glands.     Tubular  adenomata  are  usually 


TUMORS. 


.^19 


soft,  slightly  translucent,  and  somewhat  vascular.  The  tubes  are  lined 
with  cvlindric-cell  epithelium.  On  section,  when  out  transversely,  the 
tubes  appear  as  circles  possessinjj  central  lumina  and  borders  of  reyju- 
lar  cvlindric  epithelial  cells.  When  cut  lonj^itudinally.  they  often  show 
lateral  buds,  or  even  bifurcations,  the  surface  ends  of  the  irregular 
tubules  open  on  the  mucous  membrane  ;  at  the  other  end  they  terminate 
in  blind  sacs  extending  to  varying  depths ;  the  tubes  may  be  so  closely 
packed  together  as  to  show  but  little  fibrous  stroma  ;  the  cylindric  cells 
lining  the  tubes  are  usually  two  or  three  times  as  long  as  normal.  This 
varietv  of  adenoma  is  prone  to  undergo  malignant  transformation, 
manv  of  the  cancers  of  the  rectum  and  uterus  arising  '"'"m  tl'i'^  tinn'.r 


Kic.  167.— Adksom.\  of  the  Cervix  Lteri.— (From  a  sprcimen  iciil  lo  the  author  by  Dr.  E.  Q.  TkornUm) 

The  gross  specimen  was  a  strawberry  like,  pear-shaped  mass,  2.5  cm.  i     '        '  .      .     1-    >  > 1.  1-  .,  -he 

anterior  lip  of  the  rervix  uteri  just  at  the  margin  of  the  os.     Thi-  '" 

filtrated  with  paraffin,  stained  with  hematoxylin  and  cosin    and  '" 

obj.,  i-inch  DC.     The  irregularly  formed  gland  tubules,  lined  by  1,111  ■  viitiin.    .  (.iwunum.   u.    «..,     ,,~yj>a. 

Rectal  adenomata  are  most  frequently  seen  in  children,  although 
they  mav  occur  at  any  age.  They  are  strawberry-  or  raspberry-like 
turiiors,  rarely  over  one  or  two  centimeters  in  diameter,  although  the 
author  has  had  the  opportunity  to  examine  such  a  tumor  that  was  six 
centimeters  in  its  longest  diameter.  Most  observers  have  found  them 
multiple;  this  has  not  been  mv  experience.  The  glandular  structure 
imitated  is  the  gland  of  Lieberkuhn.  The  tendency  to  transformation 
into  carcinoma  (cvlindric-cell  epithelioma)  is  remarkable ;  1  have  never 
known  a  tubular  adenoma  to  persist  for  any  great  length  of  time  and 
escape  the  change.  The  same  is  true  of  a  ver>'  similar  \MmoT—ad<nomn 
of  the  cervix  uteri.      The  great  difficultv  found  in  differentiating,  histo- 


320  GENERAL  PATHOLOGY. 

logically,  between  this  tumor  and  cylindric-cell  cancer  will  be  referred 
to  when  considering  the  latter. 

III.  Neuroma.^ — A  neuroma  is  a  tumor  consisting  almost  entireh' 
of  nerve  tissue;    pure  neuromata  are  among  the  rarest  of  new  growths. 

Tumors  affecting  nerves  and  not  characterized  by  an  increase  of 
the  nerve-fibers  or  cells  are  called  false  neuromata  ;  they  may  be  circum- 
scribed or  diffuse,  single  or  multiple.  Taylor  refers  to  a  case  in  which 
during  thirteen  years  thirty-two  such  tumors  were  removed  from  the 
plantar  and  tibial  nerves ;  more  than  two  thousand  have  been  observed 
in  a  single  individual.  Histologically  the  nodules  may  be  composed 
of  adipose  tissue  {lipoiieiiroina),  myxomatous  tissue  {DiyxoiieHrorna), 
or  fibrous  tissue  {fibroiieiirom-a).  Sometimes  the  masses  are  sarcomatous 
from  the  beginning,  and  in  other  cases  malignancy  is  developed  in 
structures  initially  benign. 

The  plexiform  neuroma  is  composed  of  a  series  of  nodules  along  the 
course  of  a  nerve  or  in  a  nerve  plexus  ;  at  one  time  this  was  thought  to 
be  a  true  neuroma ;  at  present  it  is  believed  that  the  new  tissue  is  essenti- 
ally fibrous,  and  hence  the  tumor  belongs  among  the  false  neuromata 
or,  properly,  among  the  fibromata  of  nerves.  The  small  multiple  fibro- 
mata or  neuronaata  of  superficial  nerves  are  usually  hereditary.  The 
amputation  neuromata — which  consist  usually  of  fibrous  tissue,  but 
which  may  contain  partially  regenerated  nerve-fibers — form  bulbous 
masses  at  the  cut  end  of  nerves  in  stumps  after  amputation,  and  are 
intimately  connected  with  the  cicatricial  tissue  of  the  stump;  they  are 
usually  painful. 

Varieties  of  Neuroma. — Many  tumors  found  in  connection  with  the 
nervous  system  have  been  shown,  with  the  later  improved  methods,  to 
contain  a  quantity  of  nervous  tissue  insufficient  to  justify  their  special 
consideration  as  neoplasms  composed  of  that  structure.  In  theory  all  true 
neuromata  could  be  classed  under  one  of  three  heads  :  ( i)  Tumors  com- 
posed of  or  containing  ganglion  cells — ganglionic  neuromata;  (2)  tumors 
made  up  or  composed  largely  of  newly  developed  meduUated  fibers — 
myelinic  neuromata ;  (3)  tumors  composed  of  or  containing  evidently 
newty  formed  nonmedullated  nerve-fibers — amy  clinic  neuromata. 

Of  the  ganglionic  neuromata  but  little  accurate  information  is  avail- 
able. Tumors  of  this  kind  have  been  described  in  the  central  nervous 
system  and  adrenal;  they  usually  consist  of  a  matrix  in  which  there 
is  more  or  less  glia  containing  ganglion  cells.  Myelinic  neuromata 
affect  particularly  the  peripheral  nerves,  are  frequently  multiple,  and 
consist  of  tortuous  myelinic  fibrils  embedded  in  a  matrix  which  may 
be  fibrous,  myxomatous,  or  adipose.  Divided  nerve-trunks  sometimes 
develop  nodular  enlargements,  usually  affecting  the  distal  end  of  the 
proximal  fragment,  although  Durante  reports  a  case  in  which  the 
proximal  end  of  the  distal  fragment  was  affected.  Amputation  neu- 
romata belong  with  this  group  and  are  usually  thought  to  depend  upon 
ineffectual  efforts  at  regeneration.  Sometimes  such  tumors  are  ex- 
ceedingly painful  and  particularly  influenced  by  climatic  and  baro- 
metric changes.     The  racemose,  cirsoid,  or  plexiform  neuroma  develops 

^  The  exact  oncologic  position  of  neoplasms  arising  from  the  central  nervous 
system  is  still  a  matter  not  fully  determined.  Recent  researches  bearing  upon  the 
embr^'ology  and  histology  of  the  nervous  system  indicate  that  neuromata  and  glio- 
mata  may  be,  for  the  present,  considered  with  neoplasms  of  epithelial  origin. 


TUMORS. 


321 


\ 


as  fusiform  or  nodular  enlargements  involving  particularly  the  ncrve- 
Irunks  of  the  temple,  upper  eyelid,  and  back,  and  occaaionally  the 
extremities.  Histologically  the  increase  in  nerve  fibrils  is  often  incon- 
spicuous, the  overgrowth  being  largely  in  the  interstitial  tissue,  which 
is  sometimes  distinctly  myxomatous.  Tlic  tumor  is  not  frequent; 
Delfosse^  has  been  able  to  collate  eighty-eight  ca.scs. 

IV.  Glioma-  {Gluey  I'lDiior,  Virchow). — The  sustentacular  tissue 
of  the  central  nervous  system,  according  to  recent  observations,  is  a 
derivative  of  the  ectoderm,  and,  therefore,  tumors  arising  from,  or  com- 
posed of  such  elements  should  be  classified  with  the  neoplasms  of  epi- 
thelial origin.  Gliomata  are  tumors  derived  from  the  sustaining  tissue  of 
the  central  nervous  system, — the  neuroglia, — and  composed  of  glia  cells 
more  or  less  closely  imitating  the  normal  elements.  As  the  glia  cell 
differs  at  various  stages  in  its  development,  the  adult  cell  scarcely 
more  than  resembling  its  embryologic  ancestor,  so 
differ  the  cellular  elements  that  enter  into  the  forma- 
tion of  gliomata.  In  some  instances  the  tumor  is 
made  up  of  cells  showing  a  relatively  small  number  of 
fibers,  comparatively  large  in  size;  in  other  tumors 
the  fibers  are  particularly  abundant.  With  regard 
to  the  size  of  the  cell,  it  may 
be  small,  large,  or  even  ap- 
proaching the  dimensions  of 
a  giant-cell.  Again,  tumors 
occur  that  appear  to  be  ap- 
propriately classed  wnth  the 
gliomata,  and  in  which  the 
cells  more  closely  resemble 
ependyma  cells.  For  this 
class  of  tumors  Flexner  has 
proposed  the  name  cpeii- 
dyma-ccU  glioma.  Gliomata 
are  sometimes  found  contain- 
ing cellular  elements  indistinguishable  from  the  cells 
found  in  small  round-cell  sarcoma,  and,  unfortunately, 
to  such  tumors  the  name  gliosarcoma  has  been  given. 
Tumors  of  this  type  are  most  frc<|uent  in  the  eye,  ap- 
parently originating  from  the  retina.  That  some  of 
them  are  true  sarcomata  is  indicated  by  their  occur- 
rence in  the  young  (children  from  two  to  six  years);  by  their  exten- 
sion in  continuous  structures,  such  as  the  optic  nerve,  and  by  the 
involvement  of  the  contiguous  tissues;  not  uncommonly  they  produce 
fungoid  masses,  which  project  from  the  orbit;  and  they  often  recur 
after  removal.     Gliomata  of  the  brain  do  not  involve  the  membranes. 

'  These  de  Lille.  1904,  full  bibliography. 

'  LaGrangc,  "Bulletin  do  I'Acad.  dc   M6d.   Paris,      .^ylu    ..    i.joi.     New-' ' 
"Australasian  Med.  Gazette."  May.   1002.      Holuus,  "Jour.  Amer.  Med.  A.s- 
March  28,   1903,  p.  821.     Bonome,  "Virchow's  Arch.."   1901.  vol.  cl.xiii    i 
MouratotT.  "  Russki  Arkhiv  Patologii."  etc..  June  30.  1902.     Puscy.  '■': 
cage  Path.  Soc.,"  Nov.  ir.  1901,  p.  22;  also  "  y.l  :n=;  Hopkins  Hospital   . 
October.  1902,  vol.  xiii.     Mallory,  "Jour.  >'  irch."  June.  1002.  ;  .  i 

"Jour.  Med.  Research,"  Jan.,  1905.     Muth:  Saurbeck.  'Ziexler  s  B. 

1903,  vol.  34.  p.  445- 


t^  !• » •  •  V  % 


Fig.   j6g.-   ■ 


Fig.  168. — F  u  s  i  f  o  r  m 

MVXONEUROMA      OF 

THE  Externa:.  Pop- 
liteal Nerve. 
(DissECTi.NG  Room 
Speomen.) 


322  GENERAL  PATHOLOGY. 

sarcomata  do.  Glioma  contains,  in  nearly  all  instances,  medullated 
nerve-tibers;  sarcoma  rarely.^ 

Gliomata  appear  as  more  or  less  circumscribed  or  slightly  diffuse 
tumors  of  the  central  nervous  system.  As  already  indicated,  their 
consistency  is  largely  dependent  upon  the  character  of  the  cellular 
elements  that  enter  into  their  formation.  Occasionally,  the  tumor  may 
be  so  soft  that  it  can  be  handled  only  with  difficulty;  in  other  instances 
it  is  firm,  and  even  elastic.  The  color  is  dependent  upon  the  amount 
of  blood  present  and  upon  the  presence  or  absence  of  hemorrhage  or 
of  degenerative  change.  Areas  of  softening  or  even  of  cyst  formation 
are  occasionally  present.  Sometimes  these  cysts  show  an  epithelial 
lining,  the  cells  of  which  resemble  those  forming  the  wall  of  the  central 
canal.  Commonly,  but  a  single  tumor  is  present;  in  rare  instances, 
however,  the  tumor  may  be  primarily  multiple,  and  in  still  other  cases 
tumors  evidently  of  different  ages  may  be  found.  In  a  pure  glioma 
metastasis  apparently  does  not  occur.  When  rapid  growth  and  metas- 
tasis are  present,  the  tumor  is  probably  a  sarcoma. 

Site. — Brain  and  cord;  optic  nerve  and  retina;  olfactory  lobe. 

Embryonic  Epithelial  Tumors. 

Carcinomata,  or  cancers,  are  embryonic  or  atypical  neoplasms  that 
always  develop  from  epithelial  cells.  In  tumors  belonging  to  this 
group  two  essential  elements  must  be  recognized:  (i)  the  cells;  (2)  the 
stroma,  which  bounds  the  space  in  which  the  epithelial  cells  lie,  the 
space  being  known  as  the  alveolus. 

The  cells  are  characterized  by  every  diversity  of  outline;  they  may 
be  round,  oval,  squamous,  fusiform,  cylindric,  or  caudate,  and  com- 
monly possess  prominent  nuclei  and  nucleoli.  The  nuclei  may  be  single 
or  multiple,  but  are  always  large  and  usually  are  characterized  by 
strong  affinities  for  the  basic  dyes.  Variation  in  the  form  of  the  cell 
is  influenced  by  the  pressure  to  which  it  is  subjected  within  the  alveolus 
and  to  the  shape  of  the  cell  from  which  the  cancer  arose.  The  cells 
are  loosely  nested  in  the  alveoli,  and  do  not  attach  themselves  to  the 
contiguous  fibrous  tissue. 

The  amount  of  fibrous  stroma  varies:  it  consists  of  distinctly  fibril- 
lated  tissue,  arranged  so  as  to  form  irregular  spaces,  called  alveoli, 
which  communicate  with  one  another,  thereby  producing  a  continuous 
cavernous  system,  within  which  the  epithelial  cells  are  found.  The 
character  of  the  stroma  depends  largely  on  the  rate  of  growth.  If 
rapid,  it  usually  contains  round  and  spindle-shaped  cells;  if  the  growth 
has  been  slow,  or  has  ceased  altogether,  the  number  of  formative  cells 
is  small  and  the  fibrils  coarse  and  abundant.  The  latter  is  the  most 
common  condition  in  scirrhus,  the  former  in  encephaloid  cancer.  The 
stroma  not  uncommonly  contains  a  varying  number  of  unstriped  muscle- 
cells,  or  other  histologic  elements  of  the  tissue  in  which  the  neoplasm 
is  developing.  The  stroma  of  uterine  cancer  is  particularly  rich  iii 
involuntary  muscle-fibers,  and  cancer  involving  bone  may  show  areas 
of  osseous  structure.  The  blood-vessels  are  limited  to  the  stroma,  and 
do  not  pass  into  the  alveoli  or  communicate  with  the  cavities  containing 

1  For  the  stain  and  differentiation  of  glia  elements  see  article  on  Central  Ner- 
vous S5''stem,  in  Part  III. 


II    Ml  )KS. 


32.3 


the  epitlichal  masses;  ihey  have  distinct  walls  that  are  not  infre<iii<  •  '' 
thickened.     The  lymphatics  are  ])robably  continuous  with  the  al 
which    fact   accounts   for  the   fre<iuency    with    which   the   lympli-i 
are  affected.      It  is   ])rincipally  throuj^h  these  channels  that  carcii, 
spreads.     The  alveoli  were  orij^jinally  lymph-spaces,  and  therefore  com- 
municated   directly  with  the   primitive   lymphatic    ducts  draining  the 
area.     This  communication   is   not   interfered   with   by   the  growth   of 
the  cancer,  but  is  probably  facilitated  by  the  distention  of  the  primitive 
lymph- vessels  by  the  epithelial  cells.     As  already  indicated,  the  epi- 
thelium may  readily  pass  onward,  entering  the  small  hmphatic  ducts, 
and  later  the  larger  ducts,  and  eventually  the  lymph-node  or  node  chain 


Fig.  170.  -bciKRUoUi  CvKui-SoiLv  ut    M  wiua. 
•A.  Scanty  siroma  separatioi;  two  .ilvcoli.     In  thi-  upper  ri'^ht  and  lower  Irft  jmris  ol  the  lii-lil  thr  extensive  U  ■ 
and  plasma  cell  infiltration  of  the  stroma  is  well  shown.     B.  H.  B.  Cells  sliowing  atypic  niiloscs.     < 
showitiK  fusion  of  the  protopl.ism;    formation  of  the  so-called  giant  cells  of  cancer.     (  Fechnic-  Tis*'; 
in  Hcitlenhain's  corrosive  •sublimale,  paraffin  infihration,  hematoxylin,  and  Van  Gicson.     B.  and  1 
ohj..    1   im  h  ...    I 


lying  between  the  carcinomatous  area  and  the  ij.inpnatu  miui  tii.ii 
empties  into  the  vein.  The  extension  of  cancer  along  the  course  ol 
nerves — as,  for  example,  the  inferior  dental  nerve — or  along  vascular 
trunks  is  probably  due  to  the  presence  of  lymph  paths  that  follow  the 
course  of  the  vessel  or  nerve  sheath.  By  some  authors,  however,  it 
is  considered  as  a  distinct  form  or  method  of  cancerous  extension.' 

Clinical  Characters. — A  most  interesting  fact  with  regard  to 
cancers  is  the  existence  of  a  period,  preceding  the  frankly  neopla.  •.; 
growth,  in  which  certain  tissue  alterations  occur   constituting  what  are 
•See  Cheatlc.      Brit.  Med.  Jour."  Doc.   12.  1903.  p.  1515. 


324  GENERAL  PATHOLOGY. 

sometimes  called  precancerous  manifestations.^  Cancer  of  the  mamma 
may  be  preceded  by  ec?ema  of  the  nipple  or  cystic  changes  in  the  gland 
substance;  lingual  carcinoma  often  follows  a  prolonged  leukoplakia, 
and  simila-  hyperkeratoses  of  the  prepuce,  vulva,  cervix  uteri,  and  other 
mucosas  are  not  infrequent  forerunners  of  epithelioma.  Butlin  says  that 
cancer  of  the  tongue  is  usually  preceded  by  elaborate  preparations  that 
clinically  may  be  recognized  with  a  fair  degree  of  accuracy.  Chronic 
ulcerative  processes — skin  ulcers,  gastric  ulcer,  erosions  of  the  uterine 
cervix — not  uncommonly  end  in  carcinoma,  but  such  conditions  are  not 
usually  classed  with  the  precancerous  manifestations. 

As  a  rule,  carcinoma  occurs  after  the  age  of  thirty-five.  Over  fifty 
per  cent,  of  all  cancerous  growths  develop  after  the  forty-fifth  year.  The 
age  of  the  patient  is  not  so  important  as  the  evident  age  of  the  structures 
involved.  Thus,  the  author  has  seen  a  well-formed  scirrhus  of  the  breast 
in  a  patient  of  twenty-two.  The  mamma  involved,  as  well  as  its 
fellow  of  the  opposite  side,  showed  distinct  atrophic  changes.  The 
diseased  mamma  was  removed,  the  tumor  did  not  return,  and  the  patient 
passed  the  menopause  at  thirty.  Such  individuals  are  aging  prema- 
turelv,  and  in  the  diagnosis  of  cancer  such  factors  must  be  taken  into 
consideration.  The  growth  is  usually  primarily  single,  although  Warthin- 
records  two  cases  in  which  the  growth  was  multiple,  and  has  been  able  to 
find  a  number  of  more  or  less  fully  reported  instances.  Generally,  the 
tumor  is  hard.  The  so-called  soft  cancers  are  those  that  have  undergone 
some  secondary  change,  as  fatty  or  colloid,  or  are  made  up  of  epithelium 
in  excess,  as  the  encephaloid.  Cancers  tend  to  infiltrate  adjacent  con- 
nective tissues.  There  is  usually  a  central  tumor  mass,  from  which 
processes  radiate  into  the  surrounding  tissue.  Although  it  may  appear 
circumscribed,  the  border  of  the  tissue  is  never  sharply  defined;  the  typ- 
ical connective-tissue  and  epithelial-tissue  tumors,  on  the  other  hand,  are 
likely  to  have  well-defined  margins,  and,  in  most  instances,  can  be  enu- 
cleated from  the  tissues  in  which  they  lie.  Carcinoma  has  no  capsule 
and  can  not  be  enucleated. 

Secondary  carcinoma  is  usually  multiple,  possesses  a  more  sharply 
defined  or  circumscribed  border,  and,  while  it  projects  into  the  neigh- 
boring tissues,  does  not  tend  to  infiltrate  them  with  the  same  rapidity 
as  did  the  primary  tumor ;  as  a  rule,  the  mass  is  much  softer.  These 
characteristics  are  probably  due  to  the  recent  and  rapid  growth  of  the 
neoplasm. 

Secondary  Changes. — The  most  important  are  certain  fonns  of  degen- 
erative change,  among  which  is  fatty  degeneration.  This  depends  some- 
what on  the  rate  of  the  growth;  the  more  rapid  the  growth,  the  more 
rapidly  this  change  takes  place;  hence  it  is  usually  most  marked  in 
encephaloid  cancer.  Colloid  degeneration  of  the  alveolar  contents  and 
myxomatous  degeneration  of  the  connective-tissue  stroma  are  occasion- 
ally observed.  These  processes  are  particularly  marked  in  carcinomata 
involving  the  stomach.  Pigmentation,  or  melanosis  (melanotic  cancer), 
is  rare.  Calcific  deposit,  or  even  true  bone  formation,  may  occur;  they 
are,  however,  quite  infrequent.     The  cysts  occasionally  formed  in  cancer 

1  Hartzell,  "Jour,  of  Cutaneous  Diseases,"  Sept.,  1903;  also  Fink,  "Cancer 
and  Precancerous  Changes,"   London,   1903;    Robson,    "Lancet,"    Dec.    3,    1904, 

P-  1545- 

■=  "Jour.  Amer.  Med.  Assoc.,"  May.  1899,  p.  963. 


TUMORS.  325 

arise  as  the  result  of  litiucfaction  necrosis  or  of  degenerative  clianges 
in  the  celkilar  elements,  or,  probably,  in  most  instances,  are  dependent 
upon  the  presence  of  cysts  prior  to  the  carcinomatous  development. 
The  contents  of  such  cysts  may  be  fluid,  mucoid,  or  colloid  material,  and. 
in  rare  instances,  they  may  contain  more  or  less  blood;  the  extravasatcd 
blood  may  undergo  degenerative  and  necrotic  changes,  leaving  little  ol 
the  normal  constituents,  except  the  altered  l)ro\vnish  pigment,  to  be  re- 
cognized. Small  areas  of  hemorrhage  into  the  stroma  are  not  so  infre- 
quent, and  when  ulcerative  processes  have  exposed  the  surfaces,  or  when 
associated  necrosis  and  infection  are  present, — as  in  cancers  of  the 
uterus  and  stomach,  and  occasionally  in  cancer  of  the  mamman*^  gland, — 
hemorrhage  may  be  severe  and  even  fatal.  The  size  of  the  cancer  often 
bears  no  relation  to  the  amount  of  hemorrhage,  the  latter  being  apyiar- 
ently  dependent  upon  the  size  of  the  vessels  involved,  and  possibly, 
to  a  less  degree,  upon  the  activity  of  the  infective  processes. 

Various  inflammations*  and  infections  occur  in  carcinomatous  tissue. 
After  solution  in  the  continuity  of  the  superficial  covering,  infection  may 
be  marked,  and  the  systemic  phenomena  of  sepsis  may  interfere  with 
the  general  nutrition,  sometimes  demanding  operative  procedures  in 
cancers  the  extent  of  which  precludes  the  possibility  of  complete  removal. 
The  associated  infections  are  usually  pyogenic.  Numbers  of  saprophytic 
organisms  may  be  present.  Tul)erculous-  processes,  for  example,  in  the 
esophagus  or  larynx  may  become  carcinomatous,  or  an  ulcerating  carci- 
noma may  be  infected  by  tubercle  bacilli.  Tuberculosis  and  associated 
cancer  of  the  skin  have  been  observed,  and  lesions  apparently  primarily 
syphilitic,  have  become  cancerous.  Evidences  of  gumma  formation  in 
cancer  are  less  frequent,  if  ever  present.  Distinct  abscess  formation  in 
the  interior  of  carcinomatous  masses  is  uncommon.  Necrotic  processes, 
and  even  extensive  gangrene,  may  at  times  be  observed. 

Site. — The  presence  of  epithelium  being  the  essential  requisite, 
any  surface,  tissue,  or  organ  in  which  this  element  is  present  may  become 
carcinomatous.  To  a  certain  extent  the  various  forms  of  epithelium 
seem  to  influence  the  occurrence  of  different  varieties  of  cancer.  The 
cause  of  this  influence  will  become  more  evident  as  we  proceed  with  the 
consideration  of  the  forms  of  carcinoma. 

Varieties. — (I)  Epithelial  carcinoma  or  epithelioma  ;  (II)  glamiular 
carcinoma. 

The  term  epithelioma  is  used  in  a  broad  sense  by  some  writers  as 
referring  to  all  carcinomata.  It  is  here  applied  to  those  varieties  of 
carcinoma  that  usually  spring  from  epithelial  surfaces,  and  is  often  spoken 
of  as  superficial  cancer. 

I.  Epithelioma  assumes  three  important  types:  (/)  Squamous:  (2) 
cylindric-cell:  (  ,M  tuhulatrd. 

I.  Squamous  Epithelioma.  —This  variety  always  grows  from  surfaces 
covered  bv  squamous  epithelium,  either  cutaneous  or  mucous;  its  epithe- 
lial elementsclosely  resemble  squamous  epithelium;  the  distortion  in  «hape 
of  the  cell  is  due  to  the  pressure  to  which  it  is  subjected  during  r 
The  cells  penetrate  from  the  surface  epithelium  into  the  lymph  i 

the  connective  tissue,  and  follow  those  channels  that  intercommunicate. 
Occasionally,  single  isolated  epithelial  cells  may  be  recogni/.cd  in  the  ( on- 

'  Sec  Comil,  "Rev.  de  Chir.."  April  10,  1904.  p.  661. 

'  See  Moak.  "Jour,  of  Med.  Research."  June.  lOoa,  p.  128.     Bii>ii<>gr.ii'ii\ 


326 


GENERAL  PATHOLOGY. 


nective-tissue  of  the  growth.  Transverse  sections  of  the  epithehal  masses 
show  typical  nesting  of  cehs — the  so-called  concentric  globes  or  epithelial 
nests.  When  these  nests  undergo  hardening,— a  change  incident  to 
age  and  keratinization, — they  are  spoken  of  as  ''pearls,''  hence  the  term 
pearl  epithelioma.  These  yellowish  spherules,  composed  of  cornified 
or  keratinized  epithelium,  are  commonly  microscopic  bodies  situated 
within  the  alveolar  contents,  and  showing  a  marked  affinity  for  acid 
dyes,  notably  for  the  picric  acid  stains.  In  rare  instances  they  may  be 
large  enough  to  be  seen  with  the  naked  eye.  The  author  possesses  one 
specimen  of  this  kind.  The  diagnostic  importance  of  such  bodies  (they 
were  at  one  time  held  to  be  pathognomonic)  is  lessened  by  their  occur- 
rence in  other  conditions  associated  with  inflammation  of  the  skin;  they 
are  occasionally  seen  at  the  margins  of  ulcerative  processes  that  evidently 
are  not  cancers,  and  are  prone  to  occur  at  the  edges  of  the  granulating 
tissue  around  ingrowing  nails  and  in 
onychitis.  The  fibrous  stroma  may 
be  the  seat  of  some  inflammatory  in- 
filtration, particularly  if  the  ulcera- 
tion incident  to  softening  and  infec- 
tion has  occurred.  It  shows  little  of 
the  alveolar  arrangement  that  char- 
acterizes some  of  the  other  varieties 


rIP  -l-fi"^^':'. 
Fig.  171. — Squamous  Epithf.lioma. — (Gotild.) 


|lc:^ 

I  1  .  • 

0, '''  ■ ' 

Fig. 


172. — Section  ov  a  Squamous  Epithelioma. — 
{Rindfltish.)  X  500  diameters. 
The  down-growing  epithelium  in  which  are  two  cell 
nests  or  pearls,     b,  h.     The   stroma,   in  which  at 
c,  a  few  lymphoid  cells  are  to  be  seen. 


of  carcinoma.  The  ulceration,  which  occasionally  occurs  early,  may  not 
be  due  to  inflammatory  or  infective  processes,  as  is  usually  the  case,  but 
to  necrosis  and  degeneration  of  the  epithelium. 

The  growth  usually  begins  as  a  small  nodule,  situated  in  the  con- 
nective tissue  just  under  the  epithelial  layer,  with  which  it  is  continuous; 
the  skin  is  not  movable  over  the  indurated  mass.  Not  uncommonly 
the  spot  of  induration  may  appear  to  be  in  the  epithelial  layer.  As  a 
rule,  the  overlying  epithelium  is  pushed  upward,  giving  rise  to  moderate 
elevation ;  this  indurated  elevation  mav  show  slight  umbilication,  due 
to  fatty  changes,  absorption,  and  shrinking  in  its  interior,  before  super- 
ficial exfoliation  or  ulceration  occurs.  When  fully  developed,  the  can- 
cerous surface  presents  an  irregular,  ulcerated,  warty  appearance, 
and  at  times  exudes  a  clear,  or  slightly  tinged,  or,  it  may  be,  an  irrita- 


TUMORS.  ^2^ 

ting,  ichorous  tluid.     The  ukoratiun  occurs  in  the  center,  surruundeci  by 
an  indurated  margin,  beyond  which  may  be  firm  and  distinct  nodules 
There  is  often  a   distinct  tendency  toward  incrustation,    or   scabl    • 
particularly  when  situated  on  the  general  cutaneous  surface,  th« 
and   at  other  mucocutaneous  junctions.     The  scab   remains  attached 
for  a  varying  length  of  time,  and  then  falls  ofT  or  is  removed  by  tho 
patient;    after  its  removal  the  underlying  cancer,  just  described,  is 
to  be  slightly  larger  than  before  the  scab  formed.     This  gradual  incrc  , 
in  the  size  of  the  cancer,  observable  after  each  exfoliation  of  the  scab 


''    '•        •         .    4  VV.C' 

•    •    •  •,  *>.'^  . 


Fig.    173. — Cs-LiNDRic-rELL   Cancer   of   tjie   Siovacii. 
Tissue  tiled  in  corrosive  sublimate,  infiltrated  with  paraAin.  ^i.iiiu.l  uuh  luni.i!..tvliii  ..nl  i.mii.    mi  :i  ..uri!,  I 
in  balsam.     .1.  Drawn  from  i-inch  obj.,  J-inch  oc.     /<    f 
right-hand  quadrant  of  the  circle  shows  the  fully  devcl": 
the  letter  B,  shows  the  beginning  prcxluction  of  the  a\.r. 
tissue  into  the  gastric  wall.    .■Xt  C',  and  also  in  parts  of  the  licIU,  ilit  ^run^  rtatiuUts  myx<>i>Miuu»  Umuc. 

is  often  of  diagnostic  importance,  as  is  the  progressive  extension  of  in- 
duration in  the  tissue  beneath.  The  area  of  recognizable  induration  is 
not  the  limit  of  the  tumor — a  fact  always  to  be  borne  in  mind  during  its 
removal.  On  section,  the  tumor  is  firm,  and  the  fibrous  stroma  may 
be  seen  as  white  glistening  bands.  As  a  rule,  there  is  no  hemorrhage; 
there  are  few  blood-vessels  near  the  surface.  The  process  develops 
slowly,  and  glandular  involvement  may  not  occur  for  years,  although 
in  rare  instances  it  has  been  observed  within  the  first  year. 

Site. — Squamous  epithelioma  usually  occurs  at  the  junction  of  skin 
and    mucous  membrane,    or    where    two    kinds    of    epithelium    come 


328 


GENERAL  PATHOLOGY. 


together.  It  is  frequently  found  on  the  lower  lip,  nose,  penis,  scrotum, 
vulva,  anus,  and  tongue;  less  commonly  on  the  gums,  palate,  tonsils, 
larynx,  pharynx,  esophagus,  bladder,  os  uteri,  and  general  cutaneous 
surface;  rarely  on  the  hands  and  feet. 

2.  Cylindric-cell  Epithelioma  {Adenoid  Cancer,  Columnar-cell  Epi- 
thelioma, Malignant  Adenoma). — This  variety  of  cancer  is  characterized 
b}^  irregular  or  tubular  cavities,  paved  with  one  or  more  layers  of  cylin- 
dric  cells,  and  separated  by  a  stroma,  which  may  be  fibrous,  embryonic, 
or  mucoid.     In  structure  it  is  said  to  occupy  a  position  intermediate 


Fig.  174. — Section  of  Cylindric-cell  Carctnoma  of  the  Liver. 
Tissue  fixed  in  corrosive  sublimate,  infiltrated  with  paraffin,  stained  with  toluidin-blue  and  eosin,  and  mounted 
in  balsam.  Drawn  from  }-inch  obj.,  J-inch  oc.  A,  A,  A.  The  liver  tissue  adjacent  to  the  tumor.  The  re- 
mainder of  the  ticld  consists  of  three  complete  and  five  incomplete  alveoh.  Two  of  the  complete  alveoli 
occupy  the  central  portion  of  the  drawing,  while  the  third  alveolus  (practically  complete)  is  in  the  extreme 
upper  portion.  The  parts  of  alveoli  are  indicated  by  the  letters  B,  B,  B,  B.  B.  About  one  centimeter  inward, 
and  to  the  left  of  the  second  B  from  above,  a  small  area  of  hemorrhage  is  present.  A  similar  but  smaller 
area  of  hemorrhage  is  seen  just  below  the  lower  alveolus.  The  section  was  taken  from  a  primary  cancer  of 
the  liver,  which  showed,  in  some  areas,  a  structure  closely  resembhng  the  cyUndric-cell  cancer;  in  other  areas 
the  absence  of  any  intra-alveolar  arrangement  of  the  cells  leads  to  an  encephaloid  appearance.  It  will  be 
noticed  that  in  the  alveoh  shown  there  is  not  the  characteristic  cylindric  arrangement  of  the  cells  to  be  seen 
in  figure  173.  .At  some  points,  however,  there  is  seen  a  distinct  attempt  at  such  an  arrangement.  The  absence 
of  any  capsule,  or  of  any  effort  at  capsule  formation,  between  the  tumor  and  the  adjacent  hver-tissue  is  well 
shown.  An  illustration  showing  the  gross  appearance  of  this  tumor  is  to  be  found  in  the  chapter  on  the  Liver. 
Part  III. 


between  the  simple  adenoma  and  true  cancer.  The  cylindric  cells  are 
similar  to  those  that  cover  certain  mucous  or  glandular  cavities,  and 
are  always  implanted  more  or  less  perpendicularly  to  the  wall.  The 
epithelial  elements  are  similar  to  those  of  the  mucous  membrane  from 
which  they  grow,  but  differ  microscopically  from  the  arrangement  in 
the  normal  mucosa  in  the  absence  of  a  basement  membrane  (mem- 
brana  propria).  The  slower  the  growth,  the  more  nearly  typical  is 
the  attempted  gland  formation;  in  rapid  growths  and  recurrences  the 
cells  are  small  and  the  lumina  imperfect. 


TUMORS.  .^29 

Cylindric-cell  carcinomata  arc  soft,  and  arc  often  j^clatinous  in 
consistence.  On  section,  they  may  present  a  gelatinoid,  watery  ap- 
pearance. The  rale  of  growth  varies  in  diflcrent  cases,  and  often 
within  wide  Hmits;  it  is  usually  rai)id,  hut  may  be  slow.  Glandular 
involvement,  or  metastasis,  usually  occurs  early  and  t)ro£jresses  rapidly. 
In  cylindric-cell  cancer  of  that  portion  of  the  alimentary  canal  drained 
bv  the  portal  vein  metastasis  to  the  liver  is  common.  Uterine  and 
other  forms  of  pelvic  cancer  may  be  similarly  (lisscminatc<l.  Cylindric- 
cell  epithelioma,  as  a  rule,  occurs  in  younger  patients  than  does  any 
other  variety  of  epithelioma. 

These  tumors  are  usually  primary  in  the  rectum  (rectal  carcinoma 
mav  occur  very  early  in  life),  stomach,  uterus,  ovary,  gall-bladder, 
liver  and  biliar}'  passages,  or  respiratory  tract;  cylindric-cell  cancer 
mav  occur  in  any  portion  of  the  intestine.  As  secondary'  growths, 
this  variety  of  cancer  occurs  in  the  lymphatic  nodes,  liver,  lungs, 
and  kidney,  and  in  bone.  The  secondary  nodules  possess  the  same 
characters    as    the    primary  growth. 

The  most  common  forms  of  degenerative  change  are  mucoid  and 
colloid. 

As  alreadv  remarked,  cylindric-cell  cancer  resembles  very  closely 
the  tubular  adenoma.  (See  p.  318.)  The  very  close  resemblance  of 
the  two  varieties  of  tumor  has  led  observers  to  regard  them  as  possibly 
identical;  the  structural  difficulty  has  been  concealed  by  associating 
with  it  the  clinical  phenomena;  thus,  we  find  in  the  German  literature 
constant  reference  to  simple  adenoma  and  to  malignant  adenoma, 
meaning  by  the  former  the  tubulated  adenoma,  and  by  the  latter  the 
cylindric-cell  cancer  at  present  under  consideration.  It  is  evident, 
ciinicallv,  that  the  two  tumors  are  not  identical.  The  small,  straw- 
berry-like polyp  of  the  rectum,  in  children,  never  recurs  after  removal, 
and  of  the  many  specimens  of  simple  adenoma  of  the  cervix  uteri  that 
the  author  has  seen,  none  has  recurred  if  removed  early  in  life.  In 
tracing  the  cases  of  clearly  marked  cylindric-cell  cancer  not  a  single 
instance  has  occurred  in  which  recurrence  did  not  take  place  in  the 
course  of  time.  Sometimes  the  newly  formed  tubules  are  surrounded 
by  a  distinct  membrana  propria:  such  a  tumor  must  evidently  be  a 
simple  adenoma.  In  the  typical  tubules  of  the  cylindric-cell  cancer  no 
basement  membrane  is  ever  demonstrable;  in  the  cancer  there  is 
more  lawless,  purposeless,  irregular  distribution  of  the  gland-like  epithe- 
lial cells,  and  usually  a  sufficiently  prolonged  search  will  show  areas 
so  clearly  cancerous  that  the  diagnosis  can  not  be  doubted.  That  the 
simple  adenoma  mav  be  converted  into  the  cancerous  tumor  there  can 
be  no  doubt.  Admitting  this  possibility,  it  must  be  conceded  that 
intermediate  structural  gradations  occur,  and  that  occasionally  tumors 
are  found  in  which,  from  the  examination  of  a  single  slide,  it  is  quite 
impos.sible  to  state  definitely  whether  that  particular  neoplasm  is 
simple  or  malignant.  Recognizing  that  adenoma  of  this  kind  is  likely 
to  become,  without  anv  apparent  reason,  malignant  adenoma,  it  seems 
to  the  author  that  the  method  of  treatment  of  such  cases  is  at  once 
simplified — the  dangerous  character  of  all  doubtful  growths  of  this  kmd 
should  be  admitted,  and.  in  the  absence  of  positive  knowledge  to  the 
contrarv.  thev  should  be  treated  as  cancer. 

3.  Tubulated  Epithelioma  (also  variously  kno\s'n   as  Rr-l"'   '  I -^ 


330 


GENERAL   PATHOLOGY. 


Tubular  Epithelioma,  Noli  me  tangcre,  Lupus  Exedeus,  Herpes  Exedeiis, 
etc.). — This  form  of  epithelioma  is  composed  of  irregular  pavement 
epithelium  arranged  in  plugs  or  cylinders  that  anastomose  with  one 
another  and  are  embedded  in  a  stroma  consisting  of  connective  tissue, 
which  may  be  embryonic,  mucoid,  or,  more  commonly,  dense  and 
fibrous.  When  mucoid,  it  is  more  likely  to  undergo  further  degeneration 
and  to  become  cystic.  The  epithelial  nests  and  pearls  seen  in  the 
squamous  epithelioma  are  absent.  In  some  instances  the  histologic 
arrangement  resembles  scirrhus. 


Fig.  175. — Cyi.tndric-cell  Epithelioma  ok  the  Cervix  Uteri. 
The  cerNHx  and  most  of  the  body  of  the  uterus  have  been  destroyed  by  the  necrotic  process.     The  grooved  director 
shown  in  position,  passes  through  a  perforation  into  Doualas'  pouch.     The  ovary  shown  on  the  left  is  much 
enlari?ed,  and  is  apparently  invaded  at  its  point  of  attachment  to  the  uterus  behind.     The  vaginal  vault  and 
the  posterior  bladder  wall  have  been  destroyed. 


With  regard  to  the  gross  appearance  and  development  of  this  tumor, 
descriptions  have  been  given  that  evidently  include  true  lupus  (cutaneous 
tuberculosis).  The  resemblance  is  often  striking,  and  a  microscopic 
examination  is,  in  most  instances,  necessary  to  differentiate  between 
the  two  conditions.  Tubulated  epithelioma  occurs  in  the  aged;  it 
appears  on  the  mucous  membranes  earlier  in  life  than  on  the  cutaneous 
surfaces.     The  majority  of  cases  coming  under  the  author's  observation 


TUMokS.  3^1 

have  begun  on  t!ic  lower  eyelid  or  nose.  Ulceration  appears  early, 
but  progresses  very  slowly,  and  the  process  may  remain  stationary 
for  months,  or  even  for  years.  The  edges  ot"  the  ulcer  are  usually 
elevated,  irregular,  and  indurated.  The  degree  of  induration  depends 
largelv  upon  the  duration  of  the  process.  In  old,  slowly  extending 
ulceration  the  inchiration  is  more  marked  than  in  rapiflly  progressing 
lesions.  Instances  are  not  infrequent  in  which  ])artial  healing  of  the 
ulceration  has  taken  place,  and  in  which,  after  a  variable  period  of 
quiescence,  extension  has  been  resumed.  Sometimes,  without  any  dis- 
cernible cause,  the  growth  suddenly  assumes  remarkable  activity,  and 
in  a  comparatively  short  time  shows  extensive  involvement  of  adjacent 
tissues.  The  author  recalls  a  case  in  which  a  tumor  developed  on 
the  lower  evelid  as  a  small  \ilceration,  ovoid  in  outline,  and,  after  three 
vears,  its  diameter  did  not  exceed  0.5  cm.  It  was  excised  and  its 
cancerous  nature  was  satisfactorily  determined  by  microscopic  examina- 
tion. Within  a  year  a  small  recurrent  lesion  appeared  at  the  site  of 
excision,  which,  in  five  years,  showed  but  little  tendency  toward  ex- 
tension. The  tumor  then  began  active  growth,  and  inside  of  two 
months  had  involved  the  entire  lower  eyelid  and  part  of  the  cheek, 
and  had  almost  entirely  destroyed  the  eye.  Excision  was  again  at- 
tempted, but  seemed  to  exert  but  little  influence  on  the  rapidity  with 
which  the  cancer  extended. 

Glandular  involvement  is  more  uncertain  in  these  cases  than  in 
any  other  variety  of  cancer;  in  some  instances  the  spread  is  rapid; 
in  others,  slow;  in  some  cases  it  does  not  appear  at  all.  When  upon 
the  mucous  surfaces,  or  upon  the  eyelid,  the  growth  is  frequently  rapid. 

Krompecher^  describes  a  group  of  tumors  believed  to  arise  from 
the  basal  cells  of  the  Malpighian  layer  of  the  skin,  resembling,  in  some 
respects,  other  forms  of  cutaneous  epithelioma,  and  called  carcinoma 
basocellulare.  In  Emley's  series  of  35  cases,  24  of  the  patients  were 
males,  21  were  over  fifty  years  of  age;  only  one  patient  was  under 
twentv  vears.  The  average  duration  was  over  eight  years,  and  in  none 
of  the  cases  was  there  involvement  of  the  lymph-nodes.  The  tumor 
cells  are  continuous  with  the  Malpighian  layer  and  may  be  collected 
in  groups — bulbous  form — surrounded  by  narrow  bands  of  mature 
fibrous  stroma.  In  other  instances — cystic  form — small  cavities  con- 
taining turbid  fluid  are  present;  usually  the  wall  of  such  spaces  is 
formed  bv  tumor  cells,  but  occasionally  the  connective-tissue  stroma 
may  be  exposed.  In  another  group  of  these  neoplasms  the  epithelium 
extends  as  irregular  branching  projections  resembling  the  tubulated 
epithelioma  referred  to  above;  this  type  Emley  terms  the  styloid  form. 
The  fact  that  these  basal  cell  cancers  are  materially  different  from 
other  forms  of  carcinoma  is  shown  by  the  occurrence  of  encapsulation 
and  bv  their  usual  benignancy. 

Site. — The  most  frequent  location  is  on  the  face,  tongue,  and  general 
cutaneous  surface.  A  similar  but  certainly  not  identical  neoplasm  is 
occasionally  seen  in  the  intestine,  uterus,  and  ovary.  When  occurring 
in  the  skin,  the  mass  is  believed  to  develop  from  the  swcat-jrland-^.  or. 
possibly,  from  the  hair-sheaths. 

'  "Ziegler's  Beitr.."  1900.  Bd.  .xxviii.     Sec  also  Emlcy.  "Trans,  of  the  ' 
Path.  Soc.."  1904,  vol.  vi. 


332  GENERAL  PATHOLOGY. 

II.  Glandular  Carcinoma. — Varidics. — (z)  Scirrhiis;  (2)  eucephaloid 
carciiioiiuj. 

I.  Scirrhus  (Acinous  Cancer,  Clironic  Cancer,  Hard  Cancer,  Fibrous 
Carcinoma). — This  variety  of  carcinoma  is  characterized  by  the  abun- 
dance and  density  of  its  stroma  and  by  its  irregular  growth.  The 
tumor  occurs  as  a  hard,  firm  mass,  varying  in  appearance  according 
to  its  location.  In  the  mamma,  which  is  its  usual  site,  it  forms  a  hard, 
rounded  or  irregular  mass,  which  soon  becomes  firmly  attached  to  the 
subcutaneous  tissue,  and  eventually  to  the  skin.  By  the  contraction 
of  the  fibrous  stroma  it  causes  retraction  of  the  nipple  and  puckering 
or  dimpling  of  the  skin — "bacon-rind"  skin.     (See  Figs.  176  and  177.) 

On  section,  it  presents  a  grayish-white  glistening  appearance,  dotted 
with  yellow  patches  of  fatty  tissue.     The  fibrous  bands  and  fatty  areas 


^??'5?s^ 


-s'Ks.?r;3*'-r^!!ss; 


Fig.  176.— Part  of  Cutaneous  Surface  of  Right  Maiuvia,  the  Seat  of  a  Centrally  Placed,  Primary 
Scirrhous  Carcinoma  and  of  a  Secondary  Nodule 

Just  to  the  left  of  the  letter  A  is  the  nipple,  showing  the  retraction  or  umbilication,  with  puckering  or  dimpling 
of  the  skin  of  the  surrounding  areola.  The  "bacon-rind"  appearance  is  even  more  marked  just  to  the  Jett 
of  B.  To  the  right  of  C  is  a  secondary  nodule,  firmlv  attached  to  the  skm,  winch  is  drawn  in  around  the 
neoplasm;  the  surface  of  the  nodule  shows  the  stretched  skin,  which  at  the  five  pale  ovoid  or  irregular  areas 
is  greatly  thinned. 

are  more  marked  near  the  center  of  the  tumor.  Toward  the  per- 
iphery it  is  more  vascular  and  less  fibrous;  it  is  nonencapsulated.  On 
microscopic  section,  the  tissue  is  composed  of  two  structures,  connective 
tissue  and. epithelial  cells,  the  connective  tissue  or  stroma  being  arranged 
so  as  to  form  a  series  of  rounded  or  irregular  spaces  (alveoli)  in  which 
the  epithelial  cells  are  nested.  The  blood-vessel  walls  are  thickened 
and  fibrous.  Microscopic  sections  from  the  central  part  of  the  tumor 
will  show  the  connective  tissue  more  dense  and  fibrous  and  the  alveoli 
much  smaller,  with  the  epithelial  cells  small  and  atrophied,  or  possibly 
degenerated.  With  the  increase  in  the  fibrous  stroma  there  is  increased 
contraction,  causing  irregularities  of  the  surface;  when  occurring  in 
the  breast,  this  contraction  gives  rise  to  retraction  of  the  nipple — 
umbilication. 


TUMORS.  333 

During  the  development  ot  the  morbid  process  contraction  of  the 
fibrous  tissues  may  be  more  rapid  than  ejiithehal  prohf oration,  and  the 
organ  involved — for  example,  the  breast — may  actually  diminish  in 
size  with  progressive  induration;  when  this  contraction  is  marked,  the 
tumor  is  said  to  be  atrophic  or  "withering."  (See  Atrophic  Scirrhus.) 
Another  diagnostic  point  depending  upon  the  contraction  of  the  fibrous 
tissue  is  the  "cupping"  of  the  center  of  the  mass  when  divided  by  an 
equatorial  incision;  this  is  not  always  present,  but  can  usually  be 
demonstrated.  If  the  neoplasm  be  cut  in  halves  by  a  clean,  smooth 
incision,  the  central  part  of  the  cut  surface  of  each  half  retracts, 
thereby  depressing  that  part  of  the  incised  surface  below  the  surrounding 
margin — the  depressed  area  constituting  the  so-called  "cup."  (See 
Fig.  177.) 

Glandular  involvement  usually  takes  place  within  the  first  year, 
and  is  practically  always  demonstrable  by  microscopic  examination 
even  when  not  evident  to  the  unaided  eve. 


Fig.   177.— CARaxouA  op  the  Mauma;    Axial  Section  through  the    Nipple  in   F.ixe  from  Ster-vum 

TO  Axilla. 

The  depressed  nipple  occupies  the  summit  of  the  center  of  the  cancerous  area.     The  sm.-ill  drawinR  to  the  left 

shows  in  profile  the  cuppini;  of  the  incised  surface.      (Illustration  two-thirds  natural  size.) 


Glandular  carcinoma,  usually  scirrhus.  may  arise  from  cystic  proc- 
esses affecting  the  mammar\-  gland,'  particularly  that  morbid  condition 
called  cystic  disease  of  the  mamma  or  chronic  mastitis  associated  with 
the  development  of  cysts.  Some  sections  from  the  breast  studied  by 
Ellis  showed  that  the  epithelium  lining  the  cyst  cavities  was  continuous 
with  the  cells  occupying  alv-eoli  of  clearly  cancerous  areas.  Such  a 
demonstration  calls  attention  to  the  manner  by  which  the  lining  cells 
of  the  mammary  acini  may  extend  into  the  connective  tissue  of  the 
organ,  thereby  producing  carcinoma. 

The  foDiis  of  degeneration  occasionally  seen  in  hard  cancers  are  fatty. 
colloid,  mucoid,  and  hyaline,  and,  rarely,  caseous  necrosis.     Melanotic 
or  pigmentary',  and  calcareous  infiltrations  o-'Mr      Th<*  mo<;t  n^mnrk- 
able  feature  of  some  of  these  cases  is  the 
of  the  neoplasm;  nodules  that  have  developc  . 

carcinoma)  may  cease  to  grow  or  even  atrophy.     There  is  evidence  to 

'  See  Ellis.  "  Publications  from  the  Laboratories  of  •  I- 

lege  Hospital,"  1904,  vol.  i,  reprint  from  "Annals  of  Sii; 
graphy. 


334 


GENERAL  PATHOLOGY. 


show  that  even  visceral  metastases  may  manifest  retrogressive  changes. 
Instances  illustrating  this  peculiar  phenomenon  are  exceedingly  rare 
but  of  undoubted  occurrence.^  It  is  not  known  exactly  what  histo- 
logic alterations  accompany  the  disappearance,  but  probably  the  changes 
are  similar  to  those  seen  in  the  atrophic  scirrhus. 

Scirrhous  carcinoma  is  most  frequent  in  the  breast,  uterus,  stomach 
(pylorus),  esophagus,  rectum,  and  kidney;  it  is  rare  in  ovary,  testes, 
and  prostate. 


Fig.  17S. — Glandular  Carcinoma  of  the  Liver  (Scirrhus). 
Tissue  fi-xed  in  corrosive  sublimate,  infiltrated  with  paraffin,  stained  with  hemato.xylin  and  eosin,  and  mounted 
in  balsam.  Dra\\Ti  from  i-inch  obj..  A-inch  oc.  A,  A,  A,  A,  A.  Connective-tissue  stroma.  B,  B,  B,  B,  B. 
Epithelial  cells  occupying,  but  not  filling,  the  alveoli.  Communication  between  the  alveoli  is  well  shown,  as 
practically  all  the  large  alveoli  communicate.  Just  below  C  is  shown  a  small  alveolus  containing  two  epithelial 
cells,  and  a  little  to  the  right  is  a  similar  alveolus.  A  number  of  efforts  were  made  to  demonstrate  that  the 
clear  space  surrounding  the  epithelial  cells  was  occupied  by  some  material  that  would  not  stain  by  the  method 
used  in  the  section  from  which  this  drawing  was  made.  All  efforts  to  secure  such  demonstration  were  futile. 
It  is  probable  that  the  space  is  produced  by  the  contraction  of  the  epithelial  cells  during  the  process  of  fixation 
or  hardening,  or  that  the  spaces  shown  are  filled  during  life  with  some  fluid  not  coagulable  by  the  fLxing  method 
used. 


Atrophic  Scirrhus. — When  the  production  of  fibrous  tissue  pre- 
dominates, and  the  epithelium  proliferates  but  slowly,  the  resulting 
tumor  contracts  much  more  rapidly  than  it  grows.  The  epithelial  cells 
are  therefore  pressed  upon,  and  often  disappear  from  many  areas.  This 
form  of  scirrhus  is  a  breast  tumor,  and,  once  developed,  it  is  generally 
found  that  the  gland  and  tumor  progressively  diminish  in  size.  The 
malignancy  is  low,  and  if  the  fibrous  tissue  development  persists  in  its 
excess,   the  patient  rarely   succumbs.     The   writer  had   a   case   under 

^  Osier,  "Amer.  Med.,"  April,  1901;  also  Willson,  "Brit.  Med.  Jour.,"  Dec. 
20,  1902,  p.  1899. 


TU.\U)KS. 


335 


observation,  a  woman  seventy- two  years  of  age,  who  had  refused  an 
operation  nearly  twenty  Vears  previously.  The  entire  breast  of  one 
side,  and  the  overlying  and  adjacent  skin,  showed  puckering  and  con- 
traction; the  breast  of  the  other  side  was  also  invaded,  but  ulceration 
had  not  taken  place  over  either  gland.  Lymphatic  involvement  may 
be  long  delayed,  or,  in  a  few  cases,  may  not  occur.  In  the  case  just 
mentioned  there  was  very  slight  involvement  in  the  last  few  years  only. 
The  patient  died  at  seventy-four,  of  erysii)elas.  Microscopically,  such 
tumors  are  mostly  fibrous  stroma,  with  few  alveoli ;  the  contained  epithe- 
lial cells  are  advancedly  atrophied  or  degenerated    or  both. 


Fig.  i7g. — Caronoma  .\rising  in  a  NUvm*  thf  Sf^t  "f  Cy^nr  Diskacc. 

A.    Necrotic  detritus  cont.iincH  within  :i  cyst.     B.  Prolil' •  ■^''f 

shows  drsfiuamation  into  the  i  v^-t  r.n  ity.     C.  C-    I   '  "j 

linuous  with  the  epilhrlium  of  the  al\c<.li  of  a-l  .!■  ■  '"'■ 

nests  characteristic  of  this  type  of  cardnnma. 

2.  Encephaloid  Carcinoma  [Aioinuary  Canun'iuu,  .^.'ji  iuiu-r. 
Acute  Cinu\r).-T\n<.  infrciiuent  variety  of  carcinoma  is  a  soft,  rapidly 
growing,  brain-like  tumor,  in  which  the  fibrous  stroma  is  more  nearlv 
embr>-onic,  not  uncommonly  myxomatous,  and  ver>-  scantv:  tb*>  alveoli 
are  large,   and   are  filled   with 'large,   rapidly   growing   <  cells. 

The  tumor  appears  as  a  soft,  at  times  almost  fluctuating.  mass, 

which  tends  to  ulcerate  and  to  bleed  (fungus  hematfxlesj.  There  is 
earlv  involvement  of  the  skin  ("bacon  rind"),  soon  followed  by  super- 
ficial necrosis  and  ulceration.  As  a  rule,  encephaloid  carcinoma  occurs 
earlier  in  life  than  scirrhus.  and  has  been  report-'  •-   •' "      T» 


2>Z^ 


GENERAL  PATHOLOGY. 


may  occur  as  a  primary  or  secondary  growth.  The  growth  is  exceed- 
ingly rapid,  and  glandular  involvement  takes  place  early — within  the 
first  six  months.  There  is  no  retraction  of  the  nipple  when  occurring 
in  the  breast,  and  the  rapidity  of  growth  produces  a  more  clearly  cir- 
cumscribed mass  than  scirrhus;  it  is,  however,  more  rapidly  fatal. 

Primarily,  encephaloid  cancer  is  most  common  in  mammary  gland 
and  in  testes;  it  may  occur  as  a  secondary  growth  following  scirrhus, 
particularly  when  the  latter  involves  the  internal  organs.  Encephaloid 
cancer  is  much  less  common  than  scirrhus. 

Colloid  or  gelatinifonn  carcinoma  is  a  form  of  cancer  in  which  de- 
generative changes  take  place  in  the  protoplasm  of  the  epithelial  cells 
of  the  alveoli  or  in  the  connective-tissue  stroma.  The  typical  colloid 
cancer  belongs  to  the  glandular  group,  although  a  similar  change  is 
sometimes  observed  in  the  cylindric-cell  epithelioma,  particularly  of  the 
liver.  The  two  conditions  are,  however,  by  no  means  identical,  and 
are  therefore  easily  differentiated.  Gelatinous  transformation  of  glandu- 
lar  carcinomata   occurs   frequenth"   in   cancer   of  the  intestinal   canal. 


Fig.  i8o. — Encephaloid  Carcinoma  (Son  Cancer). 

—{Gould.) 
A,  A.  Stroma  made  up  of  developing  connective  tissue. 

At  the  upper  A  the  stroma  is  almost  myxomatous. 

B.  Epithelial  cells  occupying  an  alveolus;   three 

other  alveoli  are  showii. 


Fig.  i8i. — Glandular  Carcinoma  in  Which  the 
Stroma  Has  Been  Converted  into  Mucoid 
Tissue.— (GomW.") 

Note  the  stellate  cells  so  closely  resembling  those 
seen  in  my.xoma. 


particularly  of  the  stomach,  and  less  frequently  in  cancers  of  the  mam- 
mary gland,  testes,  and  ovaries.  Gelatinous  areas  are  sometimes 
found  that  no  longer  contain  any  of  the  structural  elements  by  which 
it  is  possible  to  identify  carcinomatous  processes.  In  the  younger 
parts  of  the  tumor,  however,  advancing  transformation  may  usually  be 
recognized;  a  varying  number  of  epithelial  cells  may  be  found,  centrally 
placed  in  the  alveolus,  and  surrounded  by  concentric  lamellse  of  gela- 
tinous material.  The  tumors  are  soft  and  trembling,  glassy,  and  at 
points  semitransparent.  In  the  mammary  gland  metastasis  may  be 
delayed;  in  the  stomach  rapid  extension  to  the  peritoneal  surface,  and 
more  or  less  diffuse  carcinomatosis  of  the  serous  surface,  may  be  rapidly 
developed.  (For  the  chemistry  of  colloid  and  mucoid  changes  see 
p.  248.) 

Mucoid  Carcinoma. — When  the  substance  that  distends  the  alveoli 
is  more  viscid  in  character,  it  is  believed  to  be  the  result  of  mucoid 
degeneration  of  the  intercellular  substance,  rather  than  a  colloid  change 
commencing  in  the  cell.      It  is  the  transformation  of  the  albuminoid 


TUMORS.  337 

constituents  of  the  tissue  into  a  complex  proteid  rich  in  mmin.  Until 
our  methods  ot  differentiation  become  more  accurate,  and.  until  we 
know  more  of  the  evolution  of  mucoid  and  colloid  carcinoniata,  it 
would  probably  be  best  to  consider  them  both  under  the  head  of  gcla- 
linoiis  or  (ii-latiiiiti^rni  r.mrcr. 


^■^.^^'' 


'.  ■■  v^ 


KiG.  182. — Colloid  Can'cer. — (Riudfteisch.)    X  300  diameters. 
Ihi-  stroma  has  Ijccn  hut  little  involved,  while  the  intra-alvecJar  structure  ha.s  l)cen  converted  almost  entirely  into 

KeJatiniform  material. 

Melanotic  carcinoma  is,  in  the  writer's  experience,  a  very  rare  tumor. 
It  IS  believed  that  the  pigment-forming  cells  of  epithelial  origin  are 
present  in  certain  forms  of  cancer,  and  that  melanosis  in  such  tumors 
is  due  to  the  activity  of  these  cells.  Melanotic  cancers  are  usually 
malignant  to  a  high  degree,  manifesting  a  tendency  to  metastasis  early; 
the  secondary  nodules  are  pigmented. 


CONNECTIVE-TISSUE  TUMORS. 
Adult  Coxxective-tissue  Tumors. 

I.  Lipoma  or  fattv  tumor  is  a  localized,  more  or  less  circumscribed, 
new  fonnation  of  fat.     Lipomata  are  usually  lobulated,  soft,  doughy, 
pseudofluctuating,  and  inelastic.     As  to  shape,  they  are  ovoid,  spheric, 
or  flat,  commonlv  sessile,  rarely  pedunculated.     If  encapsulated,  the 
capsule  is  exceedinglv  thin;  non-encapsulated   fatty  tumors  are  some- 
times spoken  of  as  Jijjiisc  lipomata,  the  margins  being  often  not  cl. 
defined.     Lipomata    are    rarely    multiple';  instances,    however.    - 
in  which  a  large  number  may  be  present.     The  author  recalls  a 
in  which  multiple  lipomata  situated  in  the  axilla,  groin,  and  neck 
to  the  diagnosis  of  Hodgkin's  disease.     The  diagnosis  in  this  case  was 
made  more  difficult  bv  the  presence  of  calcareous  infiltration  and  true 
bone   formation   in   the  interior  of  the   tumors,   rendering  them   more 
dense  and  causing  a  striking  resemblance  to  multiple  lymphadenomata. 
Multiple  lipomata  are  said  to  occur  in  families;  not  infrequently  the 
inherited  tendency  is  transmitted  through  several  generation^ 
»  Qucinnec,  Thdse  de  Paris.   1903. 
23 


338 


GEXERAL   PATHOLOGY 


times  the  distribution,  or  even  the  conformation  of  the  growths  is 
characterized  bv  symmetric  development  on  the  two  sides  of  the  body. 
In  some  of  these  cases  the  tumors  are  of  congenital  origin.  An  inter- 
esting phenomenon  observed  in  fatty  tumors  is  "gravity  wandering"; 
this  feature  mav  be  present  in  tumors  developing  in  the  subcutaneous 
tissues  and  possessing  slight  attachment  to  the  surrounding  structures. 
Fatty  tumors  developing  on  the  upper  portion  of  the  chest-wall,  near 
the  axilla,  or  on  the  back,  may,  in  the  course  of  time,  descend  to  the 
level  of  the  pelvic  brim,  and  lipomata  of  the  thigh  may  wander  as  far 
as  the  knee.  The  distance  traveled  and  the  rapidity  of  movement  are, 
of  course,  influenced  by  the  amount  of  attachment  and  by  anatomic 
relations. 


Fig.  183. 


Diffuse  Lipoma  of  the  Neck. 


Case  reported  by  Dr.  J.  Shelton  Horsley  in  the  "  Philadelphia  Medical  Journal,"  July  S    1899  (reproduced  by 

.    permission). 


Microscopically,  fatty  tumors  consist  of  cells  containing  fat  and  of  a 
variable  quantity  of  connective-tissue  stroma.  The  cells  are  like  those 
of  adipose  tissue,  though  usually  larger.  The  blood-vessels  are  distrib- 
uted in  the  fibrous  stroma.  If  the  fibrous  tissue  is  in  excess,  the  neo- 
plasm is  called  a  fibrolipoma,  or  fibro-fatty  tumor.  The  fibrous  fatty 
tumor,  or  fibrolipoma,  differs  from  the  simple  lipoma  only  in  the  amount 
of  fibrous  tissue  that  it  contains.  In  the  fibrolipoma  this  is  abundant; 
there  is  no  capsule,  and,  if  the  tumor  be  grasped  at  its  base  and  the  skin 
made  tense,  dimpling  of  the  cutaneous  covering  occurs;  this  result  is 
brought  about  by  the  fibrous  bands  which  traverse  the  tumor  pulling  in 
the  skin  at  their  points  of  attachment.  When  the  periphery  of  the 
neoplasm  is  sharply  outlined  from  the  adjacent  tissues,  the  tumor  is 
known  as  a  circiiniscrihcd  lipODia;  diffuse  lipomata  are  not  encapsulated 


TUMORS.  339 

and  are  continuous  witli  tlie  fatty  tissues  in  which  they  arise.      Lipo- 
mata  containing  myxomatous  tissue  are  called   niyxoliponiala. 

Cliiiiciilly,  lipomata  are  benign  tumors  of  slow  growth  and  of  variable 
size. 

The  injiltrations  and  Jci^oicrations  that  tliey  may  undergo  are  cal- 
careous infiltration  and  mucoid  degeneration,  ossification,  ulceration, 
and  cystic  degeneration;  secondary  inHammatory  and  necrotic  changes 
also  occur. 

Lipomata  may  occur  in  any  connective-tissue.  They  usually  involve 
the  subcutaneous  tissue  of  the  trunk,  especially  of  back  and  abdominal 
walls,  intermuscular  se]na.  subsynovial  and  subserous  tissues.  Lipoma 
is  rare  in  stomach  and  intestines  and  other  internal  organs.  Retro- 
peritoneal and  mesenteric  fatty  tumors  sometimes  become  very  large 
and  may  weigh  15  kilos  or  more.' 

II.  Chondroma  {Enchoiuiroina,  Enchondrosis,  Choudroid  Exosto- 
sis).— Chondromata  are  masses  of  new  tissue,  composed  of  hyaline, 
elastic,  or  white  tibrocartilage.  Chondromata  developing  from  pre- 
existing cartilage,  such  as  the  cartilages  of  the  larynx  and  trachea  and 
the  costal  cartilages,  may  assume  a  polypoid  shape,  and  are  not  uncom- 
monly multiple,  and  are  spoken  of  as  ccchoidro- 
)nata.  Developing  from  bone  or  in  tissue  not 
normally  containing  this  element,  the  cartila- 
ginous tumors  are  called  ou-hoiidrontata.  The 
term  chondroid  exostosis  is  applied  to  a  cartila- 
ginous tumor  growing  from  bone;  such  a  tumor 
mav  appear  as  a  periosteal,  subperiosteal,  or 
medullary  growth.  Cartilaginous  tumors  are 
usuallv  rounded,  smooth,  tuberous,  or  lobulated 
masses  of  very  dense  consistence;  owing  to  the 
compression  of  the  surrounding  tissues,  they 
often  appear  to  be  encapsulated;  not  uncom-  i-ic.  185.— Lip«)MA.-(Goii/rf .) 
monly,  however,  they  possess  well-marked  '^"''^f!:'X'^'t^?h"/«u*'ma"S 
capsules.     The  cut  surface  presents  a  pearly,  an- wdi  shown, 

bluish-pink  appearance,  identical  with  fresh  car- 
tilage.    As  a  rule,  cartilaginous  tumors  are  nonvascular;  but  if  vascula- 
rization occurs,  it  is  at  the  center  or  through  the  fibrous  septa.     Tumors 
composed  of  cartilage  are  most    frecjuent  in  the  young,  and  are  rare 
after  puberty. 

Microscoi)ically,  the  cells  of  the  neoplasm  resemble  those  found  in 
true  cartilage;  the  intercellular  substance  may  be  hyaline,  faintly  or 
distinctly  fibrous,  or,  in  rare  instances,  mucoid.  They  are  not,  as  a  rule, 
composed  of  dense  cartilaginous  tissue,  but  of  islands  of  cartilage  sur- 
rounded by  fibrous  septa.  The  cartilage  matrix  is  hyaline,  except  at  its 
junction  w'ith  the  fibrous  stroma,  where  it  is  usually  more  or  less  fibrous. 
Within  the  matrix  are  the  lacunas  containing  the  cartilage  cells;  these 
resemble  the  cells  of  normal  cartilage,  except  that  branching,  stellate, 
and  irregular  forms  are  frequently  present;  usually  they  are  rounded  or 
oval  in  shape.  The  lacun.'c  of  the  matrix  arc  occasionally  branched,  so 
as  to  cause  the  apoearance  of  a  series  of  star-shaped  spaces,  with  cartilage 
.hII';  King  in  their  centers 

'See  Campbell.  "Brit.  Med.  lour."  Nov.  18.  1Q03.  p.  1397 
'Lowcn.  ■Dcut.  Zeitsch.  f.  Cliir        •    -;     M!    '--v 


340  GENERAL  PATHOLOGY. 

Fatty,  calcareous,  mucoid  (most  common),  and  cystic  changes  some- 
times affect  cartilage  tumors;  ossification  may  occur,  especially  when 
the  tumor  springs  from  the  junction  of  the  epiphysis  and  shaft  of  a  long 
bone. 

Chondromata  are  most  frequent  in  tissues  that  normally  contain  bone; 
as  bones  are  developed  largely  out  of  cartilage,  it  may  be  supposed  that 
remains  of  this  structure  are  left  behind  (Cohnheim's  rests),  and  that  they 
afterward  develop  into  tumors.  Chondromata  occur  most  frequently 
on  the  metacarpal  bones  and  phalanges  of  the  hands ;  not  so  frequently 
on  the  corresponding  bones  of  the  foot.  They  are  not  infrequent  on  the 
femur  and  bones  of  the  pelvis,  in  the  last-named  situation  not  uncom- 
monly attaining  the  largest  size ;  they  also  occur  on  the  ribs  and  scapulas, 
rarelv  on  the  face  and  skull,  sheaths  of  tendons,  and  bronchial  cartilages. 
Chondromata  are  infrequent  in  the  soft  parts,  but  have  been  observed  in 
the  testicles,  ovaries,  mammae,  and  salivary  glands.  Chondroid  and 
osteoid  masses  occasionally  develop  from  the  inner  table  of  the  skull 
and  from  points  of  junction  of  the  cranial  bones  that  normally  coalesce. 
In  verv  rare  cases  chondroma  gives  rise  to  metastases,  which  may  occur 

in    the    lungs,   spleen,  brain,  liver,   and    heart. 

Michaeloff^  collected  14  such  cases. 

III.   Osteoma. — A  tumor-like  mass  of   bone 

developed  without  the  occurrence  of  inflamma- 

•  'j  *»'*''     •    V  *'ii        tion  or  incident  to  the  process  of  repair;  usually 

^^*  ^      »    '   '•  •-f '>^f        such  tumors  occur  at  the  point  of  junction  be- 

»•  -1  *      *•  *  •  ')    ,•:'         tween  a  bone  and  contiguous  cartilage.      Osteo- 

.*■*%'•     *  Vv  *  •  mata  are  classified,  according  to  their  position, 

•'*■,*  *  *»i*  •  *V»'1        ^s  (i)  exostoses,  or  those  growing  from  the  ex- 

!::i!i•^.>^>   .%..•.•':  ''        terior  of    a   bone,   and    (2)   enostoses,  or   those 

Fig.  186.— Chondroma.—  growing  from  the  interior  of  a  bone.     According 

^'^'"'^''■^  to    their    structure   they   are   divided    into    (i) 

eburnated;  (2)  compact;  (3)  cancellous  or  spongy. 

1.  Eburnated  Osteoma. — These  occur  most  frequently  on  the  inner 
table  of  the  skull,  and  are  not  uncommonly  of  syphilitic  origin.  They 
are  extremely  hard,  symmetric,  and  usually  multiple.  On  section,  the 
dense  bony  structure  is  found  to  be  composed  of  lamellae,  which  are 
arranged  parallel  with  the  surface  of  the  tumor.  In  the  lamellae  there 
are  no  blood-vessels  and  no  Haversian  canals,  but  canaliculi  similar  to 
those  found  in  the  cementum  of  the  teeth;  these  run  toward  the  surface. 

2.  Compact  Osteoma.— This  variety  is  composed  of  ordinary  com- 
pact bone,  similar  to  that  found  in  the  outer  layer  of  the  long  bones. 
Frequently  the  growth  is  nodular,  usually  beneath  or  in  the  periosteum, 
and  commonlv  affects  the  long  bones.  On  section,  it  is  found  to  differ 
from  the  eburnated  osteoma,  in  that  the  vessels  and  Haversian  canals 
run  at  right  angles  to  the  long  axis  of  the  bone.  The  tumor  possesses 
a  periosteal  fibrous  covering,  beneath  which  is  a  layer  of  small  round 
cells  (osteoblasts);  peripheral  growth  of  the  osteoma  is  accomplished 
through  the  activity  of  these  cells.  Regular  Haversian  systems  may 
be  clearly  defined. 

3.  Cancellous  or  Spongy  Osteoma. — In  this  variety  the  trabeculse  are 
very  thin  and  are  not  numerous;  the  medulla  is  embryonic  in  character, 
and  often  appears  as  a  gelatinous  mass.     In  rare  cases  it  is  distinctly 

'Quoted  by  Patel,  "Rev.  de  Chir.,"  March  10,  1904,  p.  398. 


TUMORS.  341 

fibroid.  The  whole  tumor  is  essentially. similar  to  the  spongy  tissue  of 
which  the  ends  of  loni,'  hones  and  the  bodies  of  shorter  ones  are  com- 
posed. 

Osteomata  are  benign  tumors  of  slow  growth,  usually  arrested  with 
advancing  age,  and  rarely  attaining  a  large  size.  They  are  often  heredi- 
tary and  multiple,  in  which  case  they  usually  occur  in  early  life.  Osse- 
ous growths  that  cxhil)it  malignant  characters  are  ixsh-osarconiala,  or 
sarcomata  that  have  undergone  partial  ossification  or  extensive  calcare- 
ous infiltration.  ( )steoma  may  inflame,  become  carious,  or  undergo 
)iccrosis.     Rarelv  such  tumors  are  transformed  into  sarcomata. 


■'''U>;j,^ ' ■  ?■  ■  ■■■"  ^ 


(^ 


( )sicomata  arc  most  coiniiion  m  t  <'niic(.  Lu  m  uilh  periosteuui.  ■"■m  . 
medulla,  or  cartilage.  They  may  occur  in  the  soft  parts  of  the  body,  in 
the  brain  substance,  in  the  dura  mater  and  pia  mater,  in  the  pleura, 
diaphragm,  pericardium,  in  the  skin,  in  the  choroid  coat  of  the  eye. 
in  the  air-passages,  around  or  in  hmph-nodes.  in  nerve-centers,  and 
in  tendons. 

IV.  Fibroma  (Fibroid.  Desmoid.  Slcatoma.  I  noma). — Fibromata  are 
tumors  coniposccl  of  wavy  bundles  of  fibrous  tissue. 

Simple  Fibroma.  —This  variety  is  typified  by  the  painful 
tubercle,  which  consists  of  a  nodulfe  about  the     ''<•  "'    • 


342 


GENERAL  PATHOLOGY. 


the  subcutaneous  cellular  substance.  It  is  of  firm  consistence,  and  is 
apparently  quite  circumscribed,  being  situated  loosely  in  the  cellular 
tissue  immediately  under  the  integument.  From  the  extreme  pain 
produced  by  these  small  nodules,  many  have  imagined  that  they  must 
contain  nerve-fibers;  careful  research,  however,  has  in  all  cases  failed 
to  demonstrate  the  existence  of  such  structures.  They  occur  more 
frequently  in  the  female  than  in  the  male. 

By  some  authorities  fibromata  are  said  to  be  liard  or  soft,  the  density 
being  dependent  upon  the  degree  of  development.  The  hard  or  dense 
fibroma  {fihroma  diintm)  is  of  the  type  of  dense  fibrous  tissue,  while 
the  soft  fibroma  {fihroma  molle)  is  composed  of  a  younger,  more  cellular 
growth,  containing  fewer  fibers.  The  hard  fibroma 
is  firm,  usually  lobulated,  and  encapsulated. 
The  soft  fibroma  is  much  less  dense,  and  in  texture 
resembles  the  lipoma;  it  may  be  lobulated  and 
encapsulated.  The  density  of  the  fibroma  upon 
which  the  foregoing  subdivision  is  based,  may 
be  dependent  upon  factors  other  than  the  develop- 
mental stage  of  the  fibrous  element.  Myxomatous 
transformation  of  the  intracellular  substance 
{niyxofibrojiia)  and  edema  produce  soft,  often  semi- 
fluctuating  fibrous  masses.  In  addition  to  the 
fibrous  tissue,  other  connective-tissue  elements 
mav  be  present ;  when  such  elements  are  sufficiently 
abundant,  the  condition  is  indicated  in  the  follow- 
ing manner:  For  fatty  tissue,  lipomatous  fibroma, 
or  -fihroma  Upomaiodes ;  for  bony  tissue,  ossifying 
fihroma,  or  fihroma  ossificum;  a  fibroma  rich  in 
capillaries  is  called  angiofibroma  or  telangiectatic 
fihroma,  or  fibroiia  tclangicctaiicitm. 

Neurofibromatosis^  or  Molluscum  Fibrosum 
{Fihrocelhilar  Tumor,  Dermatolysis,  Pachyderma- 
tocele).— This  variety  of  fibroma  is  a  rather  ex- 
traordinary condition,  the  chief  feature  of  which 
is  an  overgrowth,  apparently  not  inflammatory, 
of  the  fibrou-s  structure  of  the  nerves,  particularly 
those  situated  in  the  skin  and  subcutaneous  tissues. 
The  new  growth  may  affect  a  small  area,  such 
as  the  scalp,  or  it  may  involve  a 'large  extent  of 
skin  on  the  trunk  or  extremities,  or  both,  causing 
it  to  hang  in  pendulous  folds.  Sometimes  the 
tumors  form  as  separate  nodules  scattered  over 
the  skin;  thousands  may  be  present.  Any  or  all 
the  nerves  in  the  body,  except  the  olfactory  and 
optic,  mav  be  affected;  the  acoustic  nerve  is  frequently  involved. 
The  new  growth  may  be  within    the    nerve   (endoneural  variety)   or 

*  Anthony,  "Jour.  Amer.  Med.  Assoc,"  Tune  13,  1903,  p."  1630.  See  also 
"Johns  Hopkins  Hospital  Bulletin,"  vol.  xiv,  p.  204.  Rudler,  -Nouvelle  icono- 
graphie  de  la  Salpetriere."  Mav  and  June,  1904,  vol.  xvii.  Abbott  and  Shattock, 
"Trans.  Path.  Soc.  of  London."  1903,  vol.  54,  p.  231.  Fraenkel  and  Hunt,  "Med. 
Record,"  June  13,  1903,  p.  925.  Lion  and  Gasne,  ■'Bull,  de  la  Soc.  des  Hop.  de 
Paris,"  Jan.  21,  1905,  p.  5.  Richardson.  "Lancet,"  Dec.  3,  1904,  p.  1562.  Noyes, 
"Jour,  of  Path,  and  Bact.,"  Dec,   1903,  p.  240. 


Fig.  188. — XEURorrBRO- 
MATOSis. — (Pode.) 


TUMOKS. 


343 


around  the  nerve  (epineural  or  i)erineural  variety).  Microscopically, 
the  tissue  is  composed  of  fibrous  laindlcs  with  intervening  branched 
cells,  the  processes  of  which  clasp  the  bundles.  In  the  dense  fibrous 
bands  there  are  few  cells.  The  cells  are,  in  many  instances,  almost 
embryonic  in  appearance,  and  the  tissue  is  particularly  rich  in  nuclei. 
Merken  has  recentlv  studieil  fibroma  molluscum,  and  concludes  that  it 
depends  upon  some  congenital  factor  closely  allied  to  that  operative  in 
the  production  of  nevus.  Some  cases  have  been  thought  to  be  sarco- 
matous. The  cause  of  the  condition  is  unknown;  instances  of  con- 
i{enital  neurofibromatosis 


•f^SSfS^; 


have  been  recorded. 

Keloid'  {Chcloui,  Kclis). 
— This  is  a  rare  variety  of 
fibroma.  It  takes  the  form 
of  tuberous,  sausage-like,  or 
discoid  growths  seated  in  the 
corium  beneath  the  papillary 
layer. 

True  keloid  consists  of  a 
fibrous  growth  in  the  corium, 
covered  with  a  papillary 
layer;  the  papillae  and  epider- 
mis are  intact.  It  is  most 
common  in  the  negro.  It  is 
composed  of  bundles  of  coarse 
fibers,  and  in  the  early  stage 
contains  numerous  sjnndle 
cells.  Cicatricial  keloid  de- 
velops in  the  substance  of  a 
scar,  and  differs  from  the  true 
keloid  in  that  it  is  not  covered 
by  the  papil'ary  layer.  In 
other  respects  it  resembles 
the  true  keloid. 

Fibromata  originate  in 
connective  tissue,  cutis,  or 
subcutaneous  tissue,  from 
submucous  or  sul)serous 
tissue,  from  fascia,  ijerios- 
teum,  neurilemma,  or  the 
connective  tissue  of  organs 
(uterus,  ovaries,  testicles, 
mammarv  gland,  and  labium 

majus).     Clinically,  they  are  benign  tumors  of  slow  growth,  and.  with 
the  exception  of  keloid,  do  not  tend  to  recur  after  removal. 

Serous  infiltration  (as  in  molluscum  fibrosum).  mucoid  degeneration. 
fatty  degeneration  (especially  in  the  simple  til>roma  of  syphilitic  or- 
calcification  (fibroma  pctrificum),  suppuration,  and  ulceration  pi.t'- 
fibromata.    A  fairly  large  number  of  these  tvimors  develo[>  in' 

V.  Myoma. — The  myomata  are  tumors  composed  of  i 
Two  forms  of  the  myoma  are  recognized,  depending  upon  the  kind  of 
'  Ravogli.  "Jour.  Amtr.  Med.  Assoc   "    '••'"  "^.  1904.  P    -"' 


^ 


Fic.  189.  -Skition  (Lonoitidinal)  of  the  I'TrRiTS.  Show 

l.NV.    UxirORM   MYOMATTtl'S    Ksi  AIf;FMrNT. 

At  A  is  a  smiUl 
The  small 
sections  uf 
( From  <j  .' ' 
ColUgr       I 

ha.s   sliijhlh  '       ' 

ulrrinc  c;ivii\.     \\cii;lil  ul  i^iLiniuii.  i;'-?  sir,  ' 


344  GENERAL  PATHOLOGY. 

muscle  that  the  tumor  simulates.  A  tumor  composed  of  nonstriated 
muscle-fiber  is  called  a  leiomyona,  or  myoma  IcBvic  ell  alar  e ;  a  tumor 
containing  a  varying  amount  of  striped  muscle-fiber  has  been  described, 
and  is  called  rhahdomyoiiia,  or  myoma  strioccllulare. 

Leiomyomata  occur  most  frequently  in  the  uterus,  and  not  uncom- 
monly contain  more  fibrous  tissue  than  similar  tumors  occurring  else- 
where. Leiomyomata  also  occur  in  the  prostate,  tongue,  esophagus, 
stomach,  and  intestines.  As  a  rule,  this  variety  of  tumor  arises  only 
in  situations  containing  unstriped  muscle-fiber.  The  tumors  vary  in 
size.  Mvomata  of  the  intestinal  wall  are  usually  small;  myomata  of 
the  uterus  may  attain  the  size  of  a  fetal  head,  or,  in  rare  instances, 
they  mav  be  larger ;  a  number  of  instances  have  been  reported  in  which 
the  tumor  weighed  over  one  hundred  pounds.  Severanu  removed  a 
uterine  mvoma  w^eighing  195  pounds.^  Myomata  may  be  single  or 
multiple.  Multiple  myomata — when  a  number  of  tumors  occupy  the 
same  organ — give  rise  to  a  mass  the  surface  of  which  is  tuberous,  bossed, 
lobulated,  or  irregular.  Myomata  in  the  intestinal  wall  may  project 
from  the  serous  surface  as  distinct,  pedunculated  tumors.     The  same 

condition  is  possible  in  the  uterus.      Uterine 
myomata    are    said     to    be    subserous    when 
'^^'-••^*  ---^T^*  - \  situated  immediately  beneath  the  peritoneum, 

submucous  when  located   immediately  under 
the  mucous  membrane,  interstitial,  or   intra- 
mural, when  more  or  less  centrally  placed  in 
'  -"^-^    \(//  ^         ^^^®  uterine  wall.     Most  authorities  agree  that 

(•%Vv  \\vf^^  ^^^  uterine  myomata  begin  as  interstitial,  or 

.  \*i*X»°  •'!  //'^         intramural,    growths.       As    a    result    of    the 
contractile    power    of    the    normal    uterine 
>|'iM/l^\i'A>S^/'j!^^'V         muscle,  as  well   as  of   the  pressure  brought 
Fig.  i9o.-leiomyoma.-(g««w.)       "to  bear  upon  the  tumor  by   its   continuous 
The  rod-shaped  nuclei  are  sho-rni  in     enlargement,   it  is    forccd  aloug  the    line    of 
Ses'^af  fh^Xginr^an^t     least  rcsistancc,  which  must    be  toward  the 

transverse  section  in  the  center.        sCrOUS    Or    mUCOUS    COVCring.  A    SubmUCOUS 

of  the  illustration.  7  ;     ,    j         7     ^    ^i 

myoma  may  become  a  pedunculated  polyp,  the 
length  of  the  pedicle  varying  in  different  cases. 
Sometimes  the  pedicle  may  be  sufficiently  long  for  the  polyp  to  project 
from  the  os  uteri,  or  even  from  the  vulva.  Similarly  formed  subserous 
polvpi  occur.  As  a  result  of  twisting  or  kinking  of  the  pedicle  the  blood- 
supply  to  the  polyp  proper  may  be  arrested,  and  extensive  necrosis, 
or  even  gangrene,  may  occur.  Wherever  a  myoma  occurs  it  may  be 
distinctlv  circumscribed,  surrounded  by  fibrous  capsule,  or  an  ill-defined 
irregular  mass  in  the  midst  of  the  inuscle-tissue. 

Microscopicalh^  leiomyomata  are  made  up  of  elongated  spindle- 
cells,  with  rod-shaped  nuclei,  more  or  less  distinctly  grouped  into  fasci- 
culi of  various  sizes;  the  connective  tissue  varies  in  quantity.  The 
irregularly  arranged  muscle  elements  pass  in  all  directions  through 
the  tumor.  The  few  blood-vessels  present  are  found  in  the  connective 
tissue.  Occasionally,  leiomyomata  are  telangiectatic.  Such  richness 
in  blood-vessels,  however,  is  rare.  More  frequently  a  tumor  contains 
comparatively  large,  irregular  sinuses,  which,  in  the  larger  tumors,  may 
attain  a  transverse  diameter  of  from  i  to  1.5  cm.,  and  possess  a  tortuous 
MVilliams,  "Laticet,"  Sept.  23,  1899. 


TUM(JkS.  j45 

length   of   from   5    to    10  cm.      Such   irregularly    formed    cavities   '" -^ 
contain  thrombi.     (See  p.  275.) 

The  most  frecjuent  secondary  changes'  affecting  these  tumoi>  .ii< 
calcareous  infiltration  (so-called  "  womb-stone")  and  fatty  and  myxo- 
matous degenerations.  Inflammation  (due  to  injury),  abscess  forma- 
tion, ulceration,  and  other  necrotic  jirocesses  occur.  Clinically,  the 
leiomyomata  are  benign  tumors,  but  sarcomatous  transffjrmation  is 
occasionally  seen.  There  are  on  record  a  few  cases  of  generalization 
of  leinii-iNdniata.- 

Rhabdomyoma'  is  exceedingly  rare,  and  is  usually  congenital.  It 
is  not  improbable  that  tumors  of  this  class  are  met  with  only  as  a  result 
of  the  higher  evolution  of  sarcomatous  tissue  (iriyosarconui),  in  which 
the  imperfectly  developed  muscle  remains,  for  the  most  part,  in  an 
embryonic  stage.  The  muscle-hbers  present  in  rhabdomyoma  are 
irregularly  formed,  and  are  often  more  or  less  spindle-shaped  or  club- 
shaped.  As  already  stated,  the  tumor  is  in  most  instances  congenital, 
and  is  usually  found  in  the  kidney,  heart,  or  uterus. 

VI.  Angiomata  are  tumors  formed  of,  or  following,  the  type  of 
vessels — either  blood-vessels  or  lymph-vessels.  The  term  angioma  has 
been  applied  to  tumors  composed  of  blood-vessels,  and  has  that  sig- 
nificance when  used  alone.  For  the  purpose  of  description  it  is  pur- 
posed to  divide  the  angiomata  into  hemangioma  and  lymphangioma. 

(a)  Hemangiomata  are  tumors  consisting  of  blood-vessels  bound 
together  by  a  small  amount  of  connective  tissue.  Some  of  these  may 
be  composed  of  newly  formed  blood-vessels,  while  others  consist  of 
more  or  less  altered  pre-existing  vessels.  The  pure  hemangiomata  are 
composed  of  tissue  entirely  of  new  formation,  but,  by  many,  the  tumors 
formed  bv  alteration  in  pre-existing  vessels  are  included  under  this 
name. 

Simple  Hemangioma  (Simple  Xcints,  Tela}igicito»ia,  Hirth-niark. 
Mother's  Mark,  Angioma  Tclangicctoides). — This  is  the  most  common 
variety,  and  aflfects  the  skin  and  subcutaneous  tissues.  Simple  hem- 
angiomata are  flat,  slightly  elevated,  sessile  tumors  of  a  violet  or  dark- 
red  color,  rarely  bright  red  or  pink;  they  are  most  frequently  located 
upon  the  face,  around  the  orbit,  or  on  the  neck,  are  usually  congenital, 
and  after  birth  may  increase  in  size.  On  section,  the  vessels  are  found 
to  be  thin-walled  (dilated,  fusiform,  cylindric,  sacculated,  or  spheric), 
and  embedded  in  a  fibrous  or  cellulo-adipose  matrix.  There  are  usually 
two  or  more  large  vessels  that  establish  a  communication  between  the 
nevus  and  an  adjacent  artery  or  vein. 

This  form  of  angioma  is  most  frequent  on  the  skin  of  the  face,  scalp, 
neck,  and  back;  they  are  sometimes  seen  in  the  labia,  lips,  tongue, 
and  conjunctiva;  rarely  on  the  limbs.  The  varieties  of  simple  hem- 
angioma are:  (7)  Xeviis  fUimmeus  (strawberry  mark).  These  marks 
are  of  a  bright-red  color.  (2)  Xeviis  vinosus.  These  are  of  a  dark- 
red  or  port-wine  color,  and  are  known  as  port-'winc  marks. 

Cavernous  Hemangioma. — This  variety  differs  from  simple  hem- 
angioma m  that  the  vessels  are  less  tubular.  The  tumor  is  composed 
of  a  series  of  irregular  cavities  formed  by  thin,   fibrous  septa.     '^)n 

'  McDonald,  "  Tour,  .\nier.  Med.  .\ss'x:.,"  May  21.  1904.  ; 
'  De\'ic  and  Galavardin.    "Rev.  do  Chir.,"  Jan..  1004.  P 
'  Capgrand.  Thes^  de  Bordeaux.  1003. 


346 


GENERAL  PATHOLOGY. 


section,  these  cavities  appear  as  irregular  sinuses  separated  by  a  nucle- 
ated fibrous  network  of  spindle-cell  tissue.  Many  of  the  walls  are 
incomplete,  which  fact  shows  the  communication  between  the  spaces. 
The  cavity  walls  are  lined  by  endothelium.  Cavernous  hemangiomata 
are  sometimes  called  erectile  tumors,  owing  to  their  resemblance  to 
erectile  tissues,  such  as  the  corpus  cavernosum  of  the  penis.  They 
are  rarely  congenital,  and  may  develop  from  pre-existing  simple  hem- 
angioma. Usually  they  occur  early  in  life,  and  are  rare  in  old  age. 
When  this  form  of  tumor  develops  in  the  skin  and  forms  a  livid,  raised, 
and  uneven  patch,  it  is  referred  to  as  a  nevus  prominens . 

Angiomata  are  common  in  the  skin  and  subcutaneous  tissue,  and 
occasionally  are  observed  in  the  liver.  They  may  occur  in  the  kidney, 
spleen,  uterus,  intestines,  bladder,  voluntary  muscle,  bone,  mamma, 
tongue,  larynx,  subperitoneal  tissue — in  fact,  in  almost  any  vascular 
tissue. 


--  A 


^A^^'- 


Fig.  iqi. — Cavernous  Hemangioma  from  the  Wall  of  Branchial  Cyst. 
A.    Comeus  stratum.    B.    Malpighian  stratum.     C,  C,  C.  Caverns,  the  contained  blood-cells  of  which  have  not 
been  represented  in  the  drawing;  fourteen  of  these  spaces  are  present.       D,  D.  Caverns  containmg  bloorl- 
cells.     E.   Area  in  which  hemorrhage  has  occurred  in  hyaline  matrix. 

3.  Plexiform  Hemangioma  (Racemose  Aneurysm,  Aneurysm  by 
Anastomosis,  Cirsoid  Aneurysm). — Properly,  this  is  not  a  neoplasm, 
but  a  pathologic  alteration  of  the  affected  vessels.  The  vessels  become 
dilated  and  convoluted,  and,  by  pressure  on  the  intervening  tissue, 
cause  atrophy.  The  vessel- walls  are  usually  thickened.  The  tumor 
may  be  congenital  or  acquired.  When  occurring  in  the  most  super- 
ficial vessels,  it  is,  by  some,  called  a  nevus  vascvilosiis .  Plexiform 
angioma  sometimes  follows  injury.  It  usually  involves  the  scalp 
(frontal  and  temporal  region),  extremities,  labia  pudendi,  or  spermatic 
cord. 

(b)  Lymphangioma  is  a  tumor  made  up  of  dilated  lymph- vessels. 
Rarelv,   the   affected  vessels  may  form  distinct  caverns  or  sacs — the 


TUMORS.  347 

Ciivcnioit.s  lyniphaiii^^ioniii.  The  lyniplunti^ionui  cystiiitiii  is  a  form  ol 
the  cavernous  type  of  the  alTection,  characterized  by  the  presence  of 
large  cysts,  or  a  single  cyst,  usually  situated  in  the  neck  or  axilla,  but 
sometimes  found  in  the  mediastinum  or  even  the  large  viscera.'  More 
commonly,  the  masses  are  of  dilated  vessels,  and  hence  are  analogous 
to  the  telangiectatic  hemangioma  already  described.  The  altered 
structures  are  the  lymph-  and  not  blood-vessels. 

Lymphangioma  occurs  most  frecjuently  in  the  tongue  or  lip,  con- 
stituting niacroglossia  and  )iiacroclicilia  respectively.  In  both  these 
localities  the  morbid  process  is  commonly  associated  with  what  appears 
to  be  a  proliferative  change  in  the  unstripcd  muscle  present.  A  special 
form  of  lymphangioma  occurs  in  the  lymphatics  carrying  chyle  (chylous 
vessels,  lacteals),  and  is  called  a  chylangioma;  when  circumscribed  and 
comprising  a  single  cavity,  the  term  chylous  cyst  is  applied.  In  lacteal 
or  chylous  varix  the  affected  vessels  are  tortuous,  cylindric,  or  monili- 
form.-  Lymphangioma  is  usually  congenital,  but  may  not  be  evident 
or  begin  to  grow  until  some  time  after  birth. 

VII.  Lymphoma,  or  tumor  of  the  lymph-node,  covers  a  multitude 
of  conditions,  many  of  which  are  in  no  sense  tumors.  Thus,  the  glandu- 
lar enlargements  of  tubercle,  syphilis,  etc.,  are  known  as  tuberculous 
or  syphilitic  lymphomata.  To  a  related  group  belong  the  inflamma- 
tory lymphomata  that  accompany  many  infections:  c.  g.,  chancroidal 
lymphoma,  suppurative  lymphomata  of  various  kinds,  and  the  enlarge- 
ments affecting  the  cervical  nodes  in  various  throat  affections,  such 
as  diphtheria  and  scarlet  fever;   none  of  these  are  tumors. 

Lymphosarcoma  is  a  sarcoma  of  the  lymph-gland,  and  differs  but 
little  from  other  forms  of  sarcoma  except  in  such  histologic  peculiarity 
as  must  arise  from  the  site.  The  lymphatic  enlargement  that  accom- 
panies leukemia  is  probably  an  infectious  process,  with  hypertrophy  and 
hyperplasia  of  the  cells  and  stroma  of  the  lymph-nodes,  or  is  a  form  of 
sarcoma  attacking  these  structures;  the  latter  view  may  be  con- 
sidered most  popular  at  present.  Such  a  condition  is  noted  in  Hodg- 
kin's  disease,  when  the  hypertrophied  glands  are  known  as  lymphade- 
nomata.     (See  Diseases  of  the  Lymph-glands,  Part  IIL) 

VIII.  Myxoma. — This  form  of  tumor  is  composed  of  mucous  tissue, 
which  is  not,  strictly  speaking,  an  adult  structure;  it  is,  at  least,  the 
lowest  grade  of  adult  connective  tissue.  The  tissue  may  be  identical 
with  that  surrounding  the  vessels  of  the  umbilical  cord  (Wharton's 
jelly),  and  resembles  the  vitreous  humor.  The  tumor  always  contains 
a  certain  amount  of  fibnjus  stroma,  and  may  resemble  an  edematous 
fibroma.  In  fetal  life  myxomatous  tumors  are  met  with  in  those  sub- 
cutaneous tissues  from  which  fatty  tissue  is  later  developed  Macro- 
.scopically.  the  tissue  appears  as  a  homogeneous,  structureless,  gelatinous 
mass.  The  majority  of  the  cells  present  are  angiilar  and  stellate,  with 
long  anastomosing  prolongations;  others  are  indistinct  (owing  to  the 
refractorv  nature  of  the  intercellular  substance),  oval,  spheric,  or  fusi- 
form in  shape.  The  blood-vessels  are  readily  located,  but  are  few  in 
number.  Frequently,  l)etween  the  cells  fine  elastic  hbers  can  be  demon- 
strated. 

Clinicallv.  myxoma  is  a  peculiar,  soft,  gelatinous  tumor,  grayish  or 

'  See  Cystoma. 

'See  Elephantoid  Dista,sr>..  p    --lu. 


348  GENERAL  PATHOLOGY. 

reddish-white  in  color,  and  on  section  yields  a  gelatinoid,  whitish, 
albuminous,  or  mucilaginous  material.  Myxomata  usually  occur  after 
middle  life,  are  of  moderately  slow  growth,  may  be  single  or  multiple 
(commonly  multiple),  vary  in  size  (rarely  large),  and  not  uncommonly 
recur  after  removal.  This  return  may  be  due  to  imperfect  removal; 
after  which  the  remaining  myxomatous  elements 
grow  with  increased  activity.  Myxomata,  when 
arising  in  the  submucous  or  subcutaneous  tissues, 
may  be  pedunculated  or  sessile;  rarely,  the 
mass  is  lobulated.  Primarily,  they  are  benign 
tumors;  occasionally  such  a  tumor  may  become 
sarcomatous  and  the  presence  of  myxomatous 
masses  in  sarcoma  (myxosarcoma)  is  frequently 
observed.  Hemorrhage  (capillary),  if  exten- 
sive, may  convert  a  large  part  of  a  myxoma 
^It  ?^  4«i\'*"\*i  i^to  a  blood  cyst;  fatty  degeneration  is  some- 
times    present;    they    may    become    inflamed, 

Fig.  192. — Myxoma.  ,  ,   ^.,  '  ,  .-  ^ 

ulcerated,  or  necrotic. 

Myxomata  are  restricted  to  the  connective 
tissues,  from  any  of  which  they  may  arise.  They  are  most  common  in 
the  subcutaneous  and  subserous  fat,  but  also  occur  in  the  'submucous 
(nares,  uterus)  and  intermuscular  tissues.  In  periosteum  and  medulla 
of  bone,  connective  tissue  of  organs,  and  perineurium  they  are  rare. 
Myxomata  occasionally  spring  from  the  placenta. 

Embryonic  Connective-tissue  Tumors. 

Sarcoma.^ 

The  sarcomata  are  tumors  composed  of  embryonic  connective  tissue 
in  which  the  cellular  constituents  usually  predominate  over  the  inter- 
cellular substance.  The  embryonic  cells  tend  to  infiltrate  the  surroun- 
ding tissues,  as  a  result  of  which  sarcomata  are  rarely,  if  ever,  encap- 
sulated. If  a  capsule  surrounds  the  growth,  it  may  have  resulted  from 
condensation  of  adjacent  tissues,  or  it  may  be  a  part  of  the  tumor;  in 
either  case  it  is  sure  to  be  infiltrated  by  the  tumor  cells.  As  a  rule,  the 
sarcomata  contain  very  little  fully  formed  fibrous  tissue,  the  whole  mass 
being  composed  of  embryonic  cells;  the  cells  are  uninucleated  or  mul- 
tinucleated, and  rarely  possess  a  limiting  membrane;  the  shape,  size, 
and  arrangement  of  the  cells  determine  the  variety  of  the  tumor.  The 
intercellular  substance,  which  is  usually  small  in  amount,  is  closely 
connected  with  the  cells,  as  in  all  connective  tissues.  The  consistence 
of  the  tumor  depends  upon  the  character  of  the  cell  and  intercellular 
substance,  and  upon  the  presence  or  absence  of  a  fibrous  stroma.  The 
blood-vessels  are  very  numerous,  and  are  usually  in  direct  contact 
with  the  cells,  or  they  may  be  separated  from  them  by  a  layer  of  thin 
fibrillated  tissue.  The  vessels  frequently  lack  distinct  walls,  and  are 
marginated  bv  the  densely  packed  cells  of  the  neoplasm.  These  cells 
may  become  detached,  and  may  be  carried  along  in  the  current;  hence, 
sarcoma  spreads  by  the  blood-vessels.     Owing  to  the  thinness  of  the  walls 

1  Borst,  "Die  Lehre  v.  d.  Geschwulst.  m.  e.  mikroscop.  Atlas,"  Wiesbaden, 
1902.     A.  and  H.  Malherbe,  "  Recherches  sur  le  Sarcoma,"  Paris,  1904. 


TUMORS. 


^A') 


of  the  blood-vessels.  hemorrhaj,'e  into  the  parenchvma  of  the  tumor  is 
often  observed;  the  extravasated  blood  undergoes  hemolvsis.  vields 
its  contained  coloring-matter,  and  pigments  the  matrix  of  the  neoplasm. 
The  quantity  of  blood  may  V)e  large  and  form  a  cyst  within  the  tumor. 
As  will  be  seen  later,  true  melanosis  arises  froni  other  causes.  As  a 
rule,  the  periphery  of  the  tumor  is  not  clearly  defined,  there  being  no 
line  of  demarcation  between  the  sarcoma  and  adjacent  structures.  When 
the  tumor  is  of  slow  growth,  an  apparent  capsule  (pseudocapsule)  may 
be  formed  by  condensation  of  the  contiguous  connective  tissues. 

Cluneal  Characters. — As  a  rule,  sarcomata  develop  most  fre- 
quently in  early  and  middle  life,  but  may  occur  at  anv  age.  and  are 
among  the  most  malignant  of  tumors.  Th'ey  are  characterized  ])V  their 
tendency  to  extend  locally,  to  infiltrate  surrounding  structures,  to  recur 
after  removal,  and  to  give  rise  to  metastasis.     Thev  mav  be  localized. 


Fig.  IQ3. — LuNC,  Part  of  Sermus  Surkall;  i^tLu-vDARY  Sarcoiia. 
The  larger  distinctly  elevated  mas.scs  arc  the  oldest;   similar  smaller  nrxlules  arc  more  recent,  while  the  >x)un(ie»t 
growths  arc  shown  as  minute  (miliar))  grayish-white  or  white  subserous  dotlcls.     The  specimen  is  a  part  only 
of  the  lower  lobe;  reproduction  natural  size.     The  incised  surface  of  the  same  specimen  is  shown  in  Fig.  104. 

and  at  first  sharply  circumscribed;  but  are  liable  to  become  rapidly 
disseminated,  both  by  local  infiltration  and  metastasis.  Secondary' 
gro\\'ths  occur  most  frequently  in  the  lung.  Sarcomata  may  disseminate 
much  more  rapidly  than  carcinomata.  The  round-cell  and  large  spindle- 
cell  varieties  are  of  rapid  growth  and  are  very  malignant.  The  small 
spindle-cell  variety  is  much  firmer,  of  slower  growth,  and  less  malignant. 
When  suliperiosteal,  they  are  more  malignant  than  when  locate<l  in 
the  center  of  the  bone. 

Sarcomata  are  prone  to  irregularity  in  growth,  and  often  remam 
quiescent  during  long  periods.  This  phenomenon  is  more  commonly 
seen  in  primar\- tumors  than  in  metastases  or  recurrent  growths.  Usu- 
ally these  periods  of  latent  malignancy  are  brief,  but  occasionally  during 
months  or  even  vears  a  tumor  mav  cease  to  grow;  rarely  some  reduction 


350  GENERAL  PATHOLOGY. 

in  size  takes  place.  Rolleston  reports  a  case  under  the  care  of  Whit- 
ing^— an  osteosarcoma  of  the  humerus — of  fifty  years'  duration.  It  is 
possible  that  some  of  these  neoplasms  were  nonmalignant  tumors  that 
eventually  became  sarcomatous.  The  size  of  the  neoplasm  bears  abso- 
lutely no  relation  to  its  malignancy.  I  have  seen  a  sarcoma  so  small 
that  it  was  unobserved  until  it  suddenly  increased  in  size  and  gave  rise  to 
a  rapidlv  fatal  metastasis  in  the  course  of  a  few  weeks.  Wide-spread 
dissemination  of  these  tumors  (sarcomatosis)  is  due  to  the  entrance 
of  tumor  cells  into  the  circulation.  Loeper  and  Louste^  have  shown 
that  the  sarcoma  cells  may  occasionally  be  identified  in  the  blood. 
For  such  demonstration  15  or  20  drops  of  blood  should  be  allowed 
to  flow  directly  into  15  c.c.  of  a  i  per  cent,  aqueous  solution  of  acetic 
acid;  the  acid  destroys  the  erythrocytes  and,  by  centrifugalization,  the 
leukocytes  and  tumor  cells  may  be  deposited.  A  drop  of  the  sediment 
is  spread  on  cover-glasses  or  a  slide,  fixed  and  stained  in  the  same 
manner  as  blood.^  When  the  cells  of  the  neoplasm  are  small  and 
round,  it  may  be  difficult  to  differentiate  them  from  mononuclear 
leukocytes.  The  attempt,  however,  is  sometimes  successful  and  con- 
stitutes an  important  diagnostic  and  prognostic  sign. 

The  following  are  the  chief  signs  of  malignancy  in  any  tumor,  be 
it  sarcoma  or  carcinoma.  They  are  inserted  here  by  reason  of  their 
special  applicability  to  the  sarcomata: 

1.  Size  of  the  Cell. — As  a  rule,  it  may  be  said  that  the  smaller  the 
cells  of  a  tumor,  the  more  malignant  will  it  probably  be.  Thus,  the 
small  round-cell  sarcoma  is  a  more  malignant  tumor  than  that  com- 
posed of  giant-cells,  and  the  small  epithelial  cells  of  a  scirrhous  cancer 
of  the  mamma  give  rise  to  a  more  malignant  growth  than  the  large, 
flat  epithelial  cells  of  the  skin,  as  seen  in  the  squamous  epithelioma. 

2.  The  Nnmher  of  the'  Cells. — If  a  tumor  be  purely  cellular,  the 
likelihood  of  its  recurrence  is  great. 

3.  Activity  of  the  Cells. — One  of  the  chief  diagnostic  features  of  a 
malignant  tumor  is  the  tendency  of  its  nuclei  and  cells  to  divide;  if  on 
section  a  large  number  of  the  cells  show  some  stage  of  mitosis  the  prog- 
nosis is  unfavorable;  such  tumors  practically  always  manifest  rapid 
local  extension,  and  prompt  recurrence. 

4.  Shape  of  the  Cell. — A  small,  round  cell,  Hke  a  lymph  corpuscle, 
will  be  more  readily  transported  by  a  blood-vessel  or  lymphatic  than 
one  that  is  long  and  taptring;  hence  the  former  will  have  a  greater 
tendency  than  the  latter  to  reproduce  the  tumor  in  neighboring  parts. 
The  round-cell  sarcoma  forms  secondary  tumors  in  neighboring  organs, 
infiltrates  blood-vessels,  and  evinces  metastasis  with  greater  readiness 
than  one  of  the  spindle-cell  type.  The  foregoing  applies  not  only  to 
local  infiltration,  but  also  to  distal  metastases.  The  large,  irregular 
cells  of  the  squamous  epithehoma  will  be  less  likely  to  reach  distant 
parts  through  the  blood-vessels  or  lymph-vessels  than  the  small,  round, 
plastic  cells  of  a  sarcoma. 

5.  The  Manner  in  Which  the  Cells  are  Held  Together. — So  far  as 
regards  the  sarcomata,  at  least,  the  more  loosely  the  cells  are  held 
together,  the  greater  is  the  tendency  of  the  tumor  to  recur.     This  is 

^  "Brit.  Med.  Jotir.,"  Jan.  7,  1905,  p.  19. 
-  "C.  R.  Soc.  de  Biol.,"  1904,  Ivi,  p.  153. 
'  See  technic  of  Blood  Examination,  Part  III,  Chapter  I. 


TTMokS.  351 

equivalent  to  saying  that  the  nion-  tluid  the  intercellular  sul>stance, 
the  more  malignant  the  tumor.  Fluidity  of  the  intercellular  substance 
implies  that  the  neoplastic  cells  are  loosely  bound  together;  this  lack 
of  cohesion  between  the  elements  of  the  tumor  permits  of  the  ready 
dislodgement  of  one  or  more  cells,  or  masses  of  cells,  and  hence  favors 
displacement  of  the  tumor  elements  into  the  lymphatics  and  blood- 
vessels. The  fluidity  of  the  intercellular  substance  may  be  j)artly  judged 
bv  the  consistency  of  the  tumor;  a  soft,  almost  fluctuating  tumor,  pos- 
sesses but  little  firmness  in  the  intercellular  substance.  Such  soft, 
pseudofiuctuating  tumors  are  not  infrequent  among  the  sarcomata. 
The  author  has  known  of  one  or  more  instances  in  which  the  surgeon 
has  cut  into  a  sarcoma  under  the  impression  that  he  was  dealing  with  a 
cvst  or  a  cold  abscess.     Indeed,  the  cellular  elements  of  some  of  the 


Fig.  104.— I. ung.  Incised  SuRr ace  of  Part  or  One  Lobe,  Secondarv  Sarcoma. 
The  serous  surface  is  shown  in  Fig.  193.     (Natural  sire.) 

small,  round-cell  sarcomata  are  so  loo.sely  attached  that  a  needle— for 
example,  an  exploring  needle — passed  into  the  tumor  may  not  infre- 
quentlv  be  moved  about  from  place  to  place,  the  operator  not  being 
able  to  detect  the  presence  of  any  solid  constituent  within  the  mass. 

6.  Absence  of  A)iy  Tendency  to  Complete  Their  Dnrlopntenl. — Of 
all  signs  of  malignancy,  this,  in  the  case  of  sarcoma,  is  perhaps  the 
most  unequivocal.  The  cells  do  not  complete  the  formation  of  con- 
nective tissue  that  normally  they  were  destined  to  generate.  Instead 
of  their  energv  being  occupied  in  the  metabolism  necessan'  to  secrete 
the  matrix  peculiar  to  each,  it  is  wholly  expended  in  the  process  of 
reproduction.  At  certain  stages  in  the  process  of  repair  the  prolif- 
erated   cellular  elements   may  constitute   a  mass?  of   embn'onic    tissue 


352 


GENERAL  PATHOLOGY. 


which,  if  we  take  into  consideration  only  the  character  of  the  cells, 
can  not  be  differentiated  from  sarcomata  possessing  similar  cellular 
elements.  In  the  tissue  elaborated  during  reparative  processes  we 
nearly  always  see  the  cellular  elements,  in  one  or  more  parts,  progressing 
to  their  proper  histologic  end — cicatricial  tissue,  osseous  tissue,  etc.  In 
some  sarcomata  an  effort  in  this  direction  may  be  apparent.  It  is, 
however,  never  fully  successful;  if  it  were  the  tumor  would  not  be  a 
sarcoma. 

7.  Tendency  of  the  Cells  to  Spread  into  Neighboring  Inter  fibrillar 
Spaces. — In  examining  a  tumor,  the  tissues  round  about  it  should  be 
carefully  investigated,  with  a  view  to  determining  whether  the  cells 
of  the  tumor  have  invaded  adjacent  structures.  If  so,  such  a  tumor 
is  dangerous,  and  should  be  excised  with  a  wide  margin.  A  single 
cell  left  in  the  surrounding  tissue  may  reproduce  the  tumor.     Cancer 

of  the  mamma  shows  more  tendency 
to  penetrate  the  surrounding  stroma 
of  the  gland  than  perhaps  any  other 
tumor.  It  is  also  one  of  the  most 
malignant  neoplasms. 

Varieties  of  Sarcoma. — The  sub- 
division of  sarcoma  into  small  groups 
is  usually  based  on  the  size  and 
shape  of  the  cells  or  the  presence  of 
more  fully  formed  connective  tissue 
so  arranged  as  to  give  rise  to  alveoli. 
The  foregoing  bases  for  subdivision 
render  it  possible  to  recognize  (i) 
round-cell  sarcoma,  the  cells  of  which 
may  be  small  or  large;  (2)  spindle- 
cell  sarcoma,  which  also  may  be  of 
the  small-cell  or  large-cell  variety;  (3) 
giant-cell  sarcoma;  (4)  mixed-cell  sar- 
coma; (5)  alveolar  sarcoma.  To  these 
must  be  added  certain  neoplasms  in 
which  special  characters  demand  some 
additional  appellation.  When  the 
tumor  cells  elaborate  pigment,  the 
*  neoplasm  is  called  a  melanotic  sar- 
coma. The  term  osteosarcoma  has  been  appHed  to  tumors  occurring  in 
bone,  and  also  to  those  in  which  osseous  or  osteoid  tissue  is  produced; 
most  sarcomata  of  bone  contain  bone-like  structures,  and  hence  may  prop- 
erlv  be  called  osteosarcomata;  the  term,  however,  should  be  applied  for 
the  purpose  of  indicating  the  presence  of  such  tissue  in  the  neoplasm 
and  without  special  regard  to  the  particular  structure  from  which  the 
tumor  arose.  In  many  of  the  sarcomata  the  cells  are  pleomorphous, 
and  it  is  often  difficult  to  state  definitely  where  a  given  tumor  should 
be  grouped;  it  is  customary  to  classify  a  neoplasm  according  to  the 
dominant  cell  present.  Most  sarcomata  contain  more  than  one  type 
of  cell,  and  hence  would,  with  propriety,  be  designated  mixed-cell 
sarcoma.  In  the  giant-cell  sarcoma  most  of  the  cells  are  not 
of  unusual  size,  but  the  presence  of  characteristic,  large,  polynuclear 
elements  usually  justifies  the  name  given. 


Fig.  195. — Round-cell  Sarcoma. — (Rindficisch.) 
X  300  diameters. 
a.  Blood-vessels  without  distinctly  formed 
walls.  h,b.  Points  where  the  round  cells  have 
pardy  fallen  out,  showing  the  slight  basis  of 
reticular  tissue. 


fl. 


TUMORS.  353 

I,  Round-cell  Sarcoma  {EiucphaloiJ  or  Medullary  Sorcoma)  is* a 
rather  infrccjuent  torni  oi  san-oma.  and  consists  of  round  cells  with 
verv  little  intercellular  substance.  The  cells  contain  lar^c,  easily  stained 
nuclei.  Blood-vessels  are  abun<lant,  and  apj)ear  as  channels  or  sluice- 
ways passing  directly  V)etween  the  cells;  usually  lynii)hatics  cannot 
be  demonstratetl.  The  cells  rapidly  infiltrate  the  surrounding  tissues; 
the  tumor  tends  to  recur  after  removal,  and  gives  rise  to  secondary 
deposits.     The  variety  known  as  /(ir4,v  routui-cdl  sarcoma  differs  from  the 


i.  • 


_^'%^^^M. 


Fig.  iq6. — Round-cell  Sarcoma. — {Gould.)  Kic.  xgy. — Round-cell  Sarcom..    .  ^  ... ...  i.  :, — 

(Gould.) 

The  cells   have  dropped  out  at   places,  showing   the 

remaindiT  of    the  intercellular  traln-ctJiE. 

small  round-cell  variety  in  that  the  cells  are  larger  and  more  irregular 
in  size;  they  are  usually  mononuclear,  although  a  few  polynuclear 
elements  may  occasionally  be  found;  such  cells  rarely  contain  more 
than  two  nuclei  and  often  it  is  possible  to  recognize  that  these  have 
resulted  from  imperfect  division.  The  round-cell  sarcoma  may  occur 
in  any  tissue  and  at  any  age,  even  in  the  fetus  iu  iitcro.  It  is  a  soft, 
often  fluctuating,  rapidly  growing  tumor,  which,  when  on  the  surface, 
ulcerates  early,  and  usually  proves  fatal  in  a  few  months. 

2.  Spindle-cell    Sarcoma    {Recurrent    Fibroid    (Paget);    Fibroplastic 
Tumor    (Lebertj;    Fibrosarcoma;    Oat-cell    Sar- 
coma;   Fasciculated      Sarcoma). — Tumors    con- 
taining spindle  cells  are  the   most   common   of     "l^v^'v  ^<^  ';-  "" 
the  sarcomata.     They  are  firm  in  te.xture.  and      '  ^f^  1    ^^^  ^"^ 
on  section  are  translucent,  antl  grayish  or  yellow-     ^«»       •i^?^  ^     ' 
ish-white  in   color.     As  a  rule,  the  spindle-cell     ^'^^KT^^^  •  ,^5 
sarcomata    grow    much    less   rapidly    than    the     ^^a^-^^^ii^'?  ^^   O 
round-cell  variety.       They  are  divided  "into  (a)     »  ^Wfe»  V^'ff  #  i 
small-cell  and  (6)  large-cell  varieties.  ^^^^k"^/*  ~  ^  ^ 

(a)  Small  Spindle-cell  Sarcoma. — This  variety 
resembles  somewhat  the  {ibromata;  the  cells  a 
fusiform  in   shape,  with  oval   nuclei;  the  inter- 

,,     ,  ,     ^  c        \  •    \     ^\  lAii  III-    loS.— Spindleceil   Sab- 

cellular  substance,  of  which  tliere  is  very  little,  iouA.-(Gouid) 

mav  be  fibrillated.     The  cells  and   intercellular 
substance  are  rarelv  arranged   in   bundles,  but 

usually  pass  in  every  direction.  Except  that  it  is  firmer,  grows  with 
less  speed,  and  does  not  so  quickly  ulcerate  or  prove  fatal,  the  tumor 
clinically  resembles  the  round-cell  sarcoma.  Round-cell  sarcomata 
are  usuallv  round  or  oval;  the  spindle-cell  fonns  of  the  tumor  are  fre- 
quently bossed  or  tuberous;  this  latter  character  is  due  to  multi- 
centric nodules  that  have  developed  around,  or  contiguous  to,  the 
primary  mass. 

24 


sare     J?^^^^  t '^'^-^ 


354 


GENERAL  PATHOLOGY. 


Spindle-cell  sarcomata  are  most  common  in  the  periosteum,  fasciae, 
eye,  antrumi,  breast,  and  testicle,  but  may  occur  in  any  connective  tissue. 
These  tumors  tend  rapidly  to  infiltrate  the  surrounding  tissue  and  to 
recur  locally  after  removal. 

(b)  Large  Spindle-cell  Sarcoma. — This  differs  from  the  small  spindle- 
cell  variety  in  that  the  cells  are  larger,  with  prominent  nuclei  and  nu- 
cleoli, which  are  frequently  multiple;  there  is  very  little  intercellular 
substance,  with  slight  or,  it  may  be,  no  fibrillation.  The  tumor  is  likely 
to  be  very  soft,  and  is  sometimes  stained  by  extravasated  blood;  the 
growth  is  rapid  and  the  neoplasm  very  malignant.  These  tumors  fre- 
quently become  osseous  (osteosarcoma  or  osteoid  sarcoma),  especially 
when  occurring  in  the  periosteum  or  bone. 


Fig.  199. — Sarcoma  of^the  Mammary  Gland;   Tumor  of  Several  Years'  Duration;  Patient  Thirty-five 

Years  of  Age. 

.4 .  Nipple  that  appears  slightly  retracted;  this  appearance  is  not  due  to  a  pulling-in  of  the  nipjile,  as  in  carcinoma, 
but  results  from  the  forward  projection  of  the  skin  caused  by  the  enlarging  neoplasm.  B.  One  f  the  many 
secondary  bosses  over  which  the  skin  is  thin  and  shining.  These  nodules  result  from  the  polycenj-ic  local  dis- 
semination. 


3.  Giant-cell  Sarcoma  (Myeloid  Sarcoma). — This  variety  resembles 
the  spindle-cell  growths,  and  usually  occurs  in  connection  with  bone. 
Such  tumors  contain  many  large  polynucleated  cells  (see  Fig.  201), 
and  fusiform  cells  like  those  of  the  spindle-cell  varieties;  indeed,  giant- 
cell  sarcomata  are  practically  all  mixed-cell  tumors  in  which  the  giant- 
cells  constitute  more  or  less  .conspicuous  elements.  In  addition  to  the 
polymorphism  of  the  cells,  such  tumors  not  uncommonly  manifest  a 
tendency  toward  an  alveolar  arrangement.  In  properly  stained  speci- 
mens the  giant-cells  are  sometimes  sufficiently  large  to  be  easily  recog- 
nized bv  the  unaided  eye.     In  verv  rare  instances  the  giant-cell  sarco- 


;,;>V-»   '■'• 


355 


Fic.  200. — Sarcoma,  MixED-ctLL,  with  Calcification  of  Part  of  thf,  Intercelliivk  Matrix;  Osteosar- 
coma. 
.4 .  Calcified  area  in  osteoid  matrix.     B.  Osteoid  tissue  which,  in  some  areas,  gives  rise  to  an  alveolar  arrangement. 

C.  Osteoblastic  cell. 


FlC.  joi.— GlANT-CEU.  SaBCOMA.— (5^im*il  ItHi  tht  Mlkor  by  Dr.  RoitHbfTgtr  ) 

bfC.d.e.  Giant-cells.     TV    '  "       •  1   .    _    .  1   1 _  . 

like  extension  suggest r- 
tains  over  one  hundrc>l  : 
ments — the  usual  condilnTi  n.!i<i  5  111.  11  .>■.■..  mm-.  1  m.  .1  i.<  .ii.i 


■ipiid- 
'  <i>n- 
r  cle- 


356  GENERAL  PATHOLOGY. 

mata  contain  a  small  quantity  of  pigment.  The  large  giant-cells  are 
arranged  in  almost  direct  contact  with  the  other  cellular  elements,  there 
being  verv  little  intercellular  substance.  As  a  rule,  the  blood-vessels 
are  not  plentiful,  but  the  tumors  may  be  exceedingly  vascular  and 
sometimes  pulsate;  they  frecjuently  become  cystic.  They  are  usually 
firm.  Giant-cell  sarcomata  are  rare  after  middle  life,  and  are  the  least 
mahgnant  form  of  the  sarcoma;  they  usually  spring  from  the  peri- 
osteum or  endosteum.  When  they  originate  in  the  upper  or  lower  alve- 
olar process,  they  constitute  one  variety  of  the  epulis. 

4.  Mixed-cell  Sarcoma. — This  variety  contains  round  cells  (large 
and  small)  and  spindle  cells  (large  and  small),  and  otherwise  resembles 
the  round-cell  and  spindle-cell  varieties.  A  sarcoma  in  which  all  the 
cells  have  practically  the  same  size  and  shape  is  rarely  seen;  even  when 
the  cells  of  one  area  in  the  tumor  are  approximately  all  alike,  exami- 
nation of  other  areas  will  usually  disclose  cellular  elements  that  are 
quite  dissimilar.  To  this  extent  it  may  be  said  that  nearly  all  sarco- 
mata are  mixed-cell  tumors.  As  the  malignancy,  consistency,  and, 
to  a  certain  extent,  the  other  characteristics  of  a  sarcoma  depend  upon 

the  size  and  shape  of  the  cells,  it  will  at  once 

fe,  ,v»^ '---&;- e-^>  become  apparent  that  a  tumor  largely  com- 

l'^^     -^  v/V*^        ^^V-         posed  of  a  certain  cell  will  be  most  likely  to 

^^/jj||,^  S^z '^I'triv;  possess  the  attributes  with  which  that  par- 

®  t^u'V-^ft''^®^^^^^'  ticular  cell  is  commonly  endowed.     For  this 

^_^^*^^J0^^^.f/^J  reason  it  is  customary  to  speak  of  a  sarcoma 

^^iC®;^^^;:,'**^^^^^  as  spindle-cell   sarcoma,  even  though  it  con- 

*.v2s'^'  '^^■'^'-bV',- ofe,,?  tains    a    minimum   of    cells  possessing  other 

^'1  e^^^^f'-'  shapes.     The    exception    to    this    rule   is    in 

"'^''^f&  ■®'5  giant-cell  sarcoma,  where  the  giant-cells  are 

ii*^!.  #/^-*-  not  abundant    as    compared   with    the  other 

Fig.     202.— Alveol.ar     Sarcoma.—        cellular  elements. 

(Gouid^)  Alveolar  Sarcoma. — In  this  the  fibrous 

Compare   ^vith  glandular  caranoma,  ^  1  1  1  -  /tvi  r 

figures  206  and  207.  stroma  rcsembles  that  of  cancer.     Ihe  nests  oi 

cells  are  separated  by  thin  fibrous  bands.  The 
cells  are  sharply  distinguished  from  the  fibrous  network,  and  are  loosely 
adherent.  The  blood-vessels  follow  the  course  of  the  fibrous  tissue 
and  rarely,  if  ever,  enter  the  cell  groups.  In  handling  the  sections, 
should  the  nest  of  cells  drop  out,  the  remaining  fibrous  stroma  closely 
resembles  transverse  sections  of  air  vesicles  (alveoli).  Under  the  micro- 
scope there  is  no  other  variety  of  sarcoma  so  likely  to  be  mistaken  for 
carcinoma.  A  little  experience  will  usually  enable  one  to  avoid  this  error, 
particularlv  if  the  blood-vessels  in  the  stroma  be  carefully  studied.  In 
the  sarcoma  many  of  the  vessels  are  without  walls ;  in  the  carcinomatous 
stroma  the  walls  of  the  vessels  will,  in  most  cases,  be  normal,  or  may 
even  be  thicker  than  usual.  Alveolar  sarcomata  are  not  uncommonly 
melanotic.     (See  Fig.   204.) 

Melanotic  Sarcoma  {Melauosarcona). — Pigmentation  may  occur 
in  any  variety  of  sarcoma,  and  is  frequently  due  to  hemorrhage,  fol- 
lowed bv  alteration  in  the  hemoglobin  and  pigmentation.  In  certain 
forms  of  sarcoma  the  abundance  of  pigment  can  not  be  fully  accounted 
for  bv  presuming  an  antecedent  hemorrhage ;  the  tumor  cells  seem  able 
to  elaborate  pigment.  These  tumors  may  be  brown  or  slate-colored, 
and   in   some   instances   are   almost   black.     (See    Fig.    224.)     Sections 


TL'MokS. 


357 


show  the  pigment  in  and  between  the  cells.  The  coloring-matter,  con- 
tained in  neojilasms  of  this  type,  is  produced  by  special  cells  called 
niclanoblasts.      The    tumors    are    very    malignant.     Occasionally,    the 


Fig.  203. — Melanotic.  Sarcoma  Sprincint,  from  the  SiBcuTANEors  or  Possibly  from  the  Pfriostcal  Con- 
nective TissrES. 

The  intensely  dark  slate  color,  almost  black,  is  well  shou-n.  The  infiltratinR  mancins  of  the  growth  could  be  «j>- 
proximately  outlined  by  the  unaided  eye  on  account  of  ihc  intcn.siiy  of  the  pigmentation.  The  submaxillar>' 
lymphatics  were  enlarged  and  were  crowded  l»y  pigment  cells.  Histologically,  the  pigment  was  within  and  be- 
tween the  cells,  and  was  scattered  through  the  tumor  at  all  fxiints. 


'^^^^^'i 


fJki 


^' 


amount  of  pigment  produced  is  sufficient  notably  to  influence  the 
skin,  the  mucous  membranes,  and  sometimes  the  urine;  the  pigmenta- 
tion of  the  skin  may  be  intense,  giving  rise  to  a 
discoloration  resembling  that  seen  in  Addison's 
disease. 

Important  among  the  melanomata  are  cer- 
tain tumors,  frequently  arising  from  pigmented 
moles,  aV)Out  the  exact  nature  of  which  opinions 
are  divided.  Prior  to  i8qi  all  agreed  that  these 
neoplasms  were  sarcomatous;  in  that  year  Eve 
suggested  that  they  might  be  carcinomata,  and 
in  1892  Unna,  indejjendently,  urged  their  can- 
cerous nature.  Pathologists  usually  l)elieve  them 
sarcomatous,  and, following  Unna, dermatologists 
regard  them  as  carcinomatous;  owing  to  the 
wide  distribution  of  the  neoplasms  tlie  condition 

is  called  sarcomatosis  or  carcinomatosis  cutis.  The  primary  mole  from 
which  the  neo7)lasm  arises  may  show  little  or  no  enlargement  and  rarely 
attains  a  diameter  of  i  cm.  or  2  cm.  The  amount  of  pigment  in  the 
primary-  and  secondary  growths  varies  from  a  slight .  scarcely  demonstrable 


Fio.    J04 

NOTIC      SaK' 


35S 


GEXERAL  PATHOLOGY, 


quantity  to  such  an  abundance  that  the  neoplasms  are  almost  black,  the 
skin  irregularly  mottled,  and  the  coloring-matter  excreted  in  the  urine. 
In  the  tumors  the  pigment  appears  to  be  melanin  and  in  the  urine 
colorless  melanogen,  which,  by  oxidation — exposure  to  the  air  or  treat- 
ment with  chemic  oxidizers — becomes  perceptible;  occasionally  a  true 
melanuria  may  be  present.  The  tumors  are  exceedingly  malignant,  the 
patients  rarely  surviving  more  than  one  or  two  ^^ears.^ 

Endothelioma  {Plexiform  Angiosarcoma). — In  this  variety  of  neoplasm 
the  cell  nests  are  formed  by  proliferation  of  endothelial  cells.  The  tumor 
is  highly  vascular,  due  either  to  pre-existing  or  to  newly  formed  vessels, 
the  walls  of  which  become  thicker,  until  at  length  the  intervascular 
spaces   are    entirely  filled.      Endotheliomata    occur    in    the    arachnoid 


Fig.  205. — Cerebru.m,  Cukosal  Section,  Anterior  Aspect;  Superior  Parietal  Lobule  and  Posterior  Pakt 
OF  Temporal  Lobe.  (Three-fifths  Natctral  Size.) — (Jefferson  Medical  College  Hospital  Laboratories, 
N'o.  2538.) 

Melanotic  sarcoma,  secondarj'  to  primary  growth  in  pigmented  mole  of  skin  of  back.  A .  Secondary  nodule,  show- 
ing considerable  hemorrhage  in  the  interior  of  the  new  growth  and  a  scanty,  irregularly  distributed,  but  narrow 
band  of  peripheral  hemorrhage.  B.  Similar  mass  in  opposite  hemisphere.  The  hemorrhage  in  this  area 
is  around  the  growth,  which  is  considerably  compressed.  C.  Blood-stained  zone  surrounding  mass;  it  wUl 
be  observed  that  the  peripheral  blood  tinging  of  the  white  matter  is  more  marked  on  this  side  than  the  other, 
due  to  the  more  abundant  hemorrhage  and  its  peripheral  chstribution.  D  and  E.  are  also  areas  of  hemor- 
rhage containing  varying  quantities  of  neoplastic  tissue;  the  latter  which,  in  the  absence  of  extra vasated  blood 
is  grayish-brown  or  nearly  black,  is  further  obscured  by  hemoglobin  imbibition. 


and  pia  mater,  and  usually  on  serous  surfaces,  but  have  been  observed 
in  the  viscera,  bone,  mamma,  and  subcutaneous  tissues;  the  parotid 
neoplasm  known  as  a  "mixed  tumor"  is  often,  if  not  always,  an  endo- 
thelioma. Occasionallv,  when  occurring  in  the  pia  mater,  the  proliferated 
endothelial  cells  are  aggregated  into  small,  spheric  nodules  of  a  peculiar, 
shiny,  pear-like  appearance;  the  tumor  is  then  referred  to  as  a  chole- 
steatoma. Endotheliomata  not  uncommonly  assume  a  distinctly  alveolar 
type.  The  large,  flat,  endothelial  cells  springing  from  the  serous  surface, 
and  occurring  within  distinct  alveoli  formed  of  connective  tissue,  afford  a 

^  The  literatiire  of  the  subject  may  be  traced  from  the  following:  Eve,  "Prac- 
titioner," Feb.,  1903,  p.  165.  Wilson  and  Kalteyer,  "Amer.  Jour,  of  Med.  Sci.," 
Nov.,  1903,  p.  751. 


TIT.MOKS. 


359 


picture  so  closely  rescniMinj:;  carcinomata  that  anurato  ditTerentiation 
seems  at  times  impossil)k\  This  close  resemlilanoc  has  led  to  an  un- 
fortunate complication  of  names,  such  tumors  hcin;^  sometimes  called 
tiuiotliclial  carcitionmta,  and,  aj:[ain,  cpillwlionuitu  of  the  serous  mem- 
l>ranes.  Usually,  a  careful  examination  of  a  large  numlicr  of  sections 
will  disclose  areas  distinctly  sarcomatous.  The  shape,  arrangement,  and 
character  of  the  cells,  associated  with  the  ])oor  development  of  the 
blood-vessels,  point  conclusively  to  the  diagnosis  of  sarcoma.  The 
author  has  recently  had  an  opportunity  to  examine  such  a  tumor  spring- 
ing from  the  tonsil  or  pharyngeal  wall.  The  examination  of  many 
sections  has  led  the  writer  to  believe  that  it  is  not  impossible  that  some 
of  these  tumors  mav  rei)resent  coml)ined  or  associated  processes;  the 
coincidence  of  sarcoma  and  carcinoma  in  the  same  individual,  or  even  in 
the  same  organ,  occasionally  occurs;  the  author  has  seen  giant-cell 
sarcoma  and  scirrhus  together  in  the  female  mamma.  Tumors  of 
endothelial  origin  arising  from  the  cells  in  the  lym])h-spaces  are  called 


i-  11..    .'OO.  --.\1aM.\IA,    LY»U>HA.Nl.;iO-E.SlJOTllhl.l<lMA. 

Removed  by  Prof.  J.  Chalmers  D.iCosta.   Section  of  thi.s  tumor  is  shown  in  Kite,  jot- 

lymphangio-endotheliomata ;  tlK.sc  developing  from  the  endothelium 
of  the  blood-vessels,  hemangio-endotheliomata.  Apparently  some  of 
these  neoplasms  arise  from  the  j.erivascular  endothelium,  and  to  these 
has  been  given  the  name  perithelioma.  With  regard  to  the  malignancy 
of  the  endothelioma,  it  mav  be  state.l  that,  as  a  rule,  they  grow  slowlv. 
manifest  metastasis  late,  if  at  all.  an«l  evince  little  tendency  to  recur  if 
thoroughlv  removed.  The  high  mortality  from  endothelioma  is  due 
to  inaccessibilitv  of  the  tissues  ordinarily  involved.' 

Psammoma  (.•lH.j^io/z7/nV  Sanowa)  is  a  peculiar  tumor,  contaming 
sand-like  masses  and  originating  in  the  brain  and  its  membranes,  more 

I  may  be  found  in.  or  traced 
Mil.    'Munch,  tncd.  Woch.." 

34.  n.  741.      Keen.  "Jour.  .-\mcr.  .M-M    .»--<.."  A- ■       •        I">l. 

•Amer.  Med.."  Julv  16.  1004.  V-  'oq.  Gilford  and  Davis.  •  !'• 
p.  729.  Kirchner',  "Deut.  militar.  Zeit.."  1905.  H..i.  1 
•Trans.  Path.  Soc.  of  London."  1903.  vol.  54.  p.  320 


'  The  important  literature  bearing  on  cik' 
from,  references  given  in  the  following  articl' 
April  26.  1Q04.  ri.  741.      Keen.  "Jour.  Amer.  .M-  w    .» 


36o 


GEXERAL  PATHOLOGY. 


particularly  in  the  pineal  gland  and  the  choroid  plexus;  it  contains  fine, 
chalky,  or  calcareous  concretions  showing  concentric  lamination.  Col- 
loid or  hyaline  change  may  occur  in  or  near  the  concretions;  indeed, 
if  the  lime  salts  be  cautiously  dissolved  by  acids,  a  concentrically  ar- 
ranged hyaline  matrix  commonly  remains.  The  occurrence  of  similar 
calcific  deposits  in  tumors,  the  tissues  of  which  approach  the  adult  type, 
shows  that  the  presence  of  calcareous  deposit  is  not  restricted  to  sar- 
coma, but  may  be  seen  in  other  growths  developing  in  the  areas  indi- 
cated. 

Chloroma^  is  another  oddly  formed  cellular  tumor;  a  section  of  the 
gross  specimen  presents  a  light  green  or  dirty  brown  color,  which  soon 
fades  on  exposure  to  air.      Its  cause  is  not  known;  it  occurs  chieflv  in  the 


Fig.  207. — MAiuu,  Lymphaxgio-endothelioma. 
In  die  upper  right  quadrant  is  the  margin  of  a  mammary  duct.     Section  of  mamma  shown  in  Fig.  206. 


periosteum  of  the  skull,  but  mav  involve  the  subcutaneous  tissues,  mus- 
cles, viscera,  and  lymph-nodes  (chlorolvmphoma).  The  blood  frequentlv 
shows  a  mononuclear  leukocytosis  resembling  that  of  lymphatic  leuke- 
mia. Histologically  the  tumor  is  composed  of  a  scanty  reticulum  and 
cells,  the  latter  resembling  the  large  Ivmphocytes  of  the  blood;  occa- 
ionally  granules  are  found  both  within  and  between  the  cells.  Some 
cases  are  accompanied  by  the  hemorrhagic  diathesis. 

Cylindroma  is  produced  by  partial  hyaline  or  mucoid  degeneration 
of  a  sarcoma,  or  when  there  is  a  combination  of  sarcomatous  and  myxo- 
matous tissue.  The  term  is  also  applied  to  a  variety  of  tumor  of  the 
epithelial  type,  known  as  cylindroma  carcinoinatodes,  which  is  character- 

'  See  Dock  and  "Warthin,  "Trans,  of  Assoc,  of  Amer.  Physicians,"  1904. 


TUNUJKS.  361 

ized  by  the  formation  of  peculiar  homogeneous  spherules  within  the 
cell  nests;    it  is  probably  a  colloid  degeneration. 

Sarcomata  are  particularly  liable  to  secondary  change.  Areas  in 
the  tumor  may  show  a  deciiled  disposition  to  complete  the  develop- 
mental temlency  of  connective  tissue.  As  a  result  of  such  processes 
true  bone  formation  may  occur — ostcosanoina:  or  cartilage  may  be 
produced — choiiJrijyiiii;  or  iluvidroid  .siircotna,  or  chondrosarcoma. 
Lipomatous  sarcomata  are  rare.  Sarcomata  containing  more  or  less 
mucoid  tissue  {myxosarcoma)  are  more  frequent.  In  such  tumors  the 
change  may  be  conspicuous  in  the  intercellular  substance,  or  it  may  be 
evident  within  the  cells  themselves.  Conversion  of  the  tumor  cells 
into  a  structure  resembling  adult  fibrous  tissue  has  already  been  referred 


^^;^::^m^^^^: 

,^:^Ci^B%-'     '   • 

%.. 

jp^r^';.  •„:■-■.                 ...  ■: 

■;Z/.i> ■'-    r;     k-    ■■■■•     ,,    -•■     '               "   "■•  ^-  " 

-        .  ■  •'-•     .■  ^•''■" 

i^'X-'.  *-"'.  'r;  ,':  v^v'"  /.  ;,,  •'  ■    '\'\  , 

.■   ' ."  ■■  '  ■   ' 

'  • 

■\     ■  ^^ 

■s-x 

•^•'         ;,X      ."'■-  '  ''"'■     •'■.    v'-^'a 

'   ."'      ■ 

•  ^ 

:£^^^^ 


Fig.  208. — Perithelioma  of  the  Carohk  Body. 
Ixitz  24  mm..  Oc.  A.     Rcluced  one-half. 


to  in  considenng  hbrosarcoma.  (.)t  the  innitratiMns  m  wiii.ii  sanoiiKii.i 
are  liable,  calcification  is  the  most  common.  Such  tumors,  containing 
calcific  collections  or  concretions,  are  sometimes  called  osteoid  sarco- 
mata, a  name  which  is  particularly  objectionable  as  it  resembles  so 
closelv  osteosarcoma,  a  term  applied  with  an  entirely  different  meaning. 
Fattv  degeneration  of  sarcoma  cells  occasionally  occurs.  Sometimes 
the  distinctly  fatty  areas  are  conspicuous,  and  may  be  easily  recog- 
nized as  more  or  less  irregular,  yellowish  |)atches.  Cyst  formation 
in  the  interior  of  sarcomata  is  occasionally  observed;  it  is,  however,  a 
comparativelv  infrequent  change. 

As  a  result  of  the  faulty  development  of  the  blood-vessel  walls, 
areas  of  interstitial  hemorrhage  are  not  infrequfent.     '"'  assume 


362 


GENERAL  PATHOLOGY. 


the  character  of  a  suffusion,  the  blood  infiltrating  between  the  tumor 
cells;  more  or  less  circumscribed  areas  of  hemorrhage  may  also  occur. 
When  infection,  ulceration,  or  superficial  necrosis  has  removed  the 
overlying  skin  or  mucous  membrane,  sarcomata  not  uncommonly  bleed, 
even   profusely.      With   the   lessened    pressure  resulting  from  destruc- 


FiG.  209. — Perithelioma  or  Carotid  Body. 
Obj.  B.  and  L.  J-inch,  oc.  i  inch.     Reduced  one-half.     A.  Red  blood-cells  in  an  alveolus. 

stroma  between  alveoli. 


B.  Blood-vessel  in  the 


tion  of  the  overlying  skin  or  mucous  membrane  the  neoplasm  may 
protrude  as  a  fungoid  growth,  more  or  less  narrowed  at  its  base,  and 
constituting  a  form  of  the  fiingits  hcmatodcs  of  the  older  writers.  In- 
fectious changes  in  the  sarcomata  may  be  evident.  Extensive  necrosis 
of  the  cells  resulting  from  infection,  and  even  gangrene  of  a  large  portion 
of  the  tumor,  may  occur.  Such  ulcerating  surfaces  may  suffer  sapro- 
phytic infection,  and  give  off  a  penetrating,  fetid  odor.  The  patient's 
health  may  be  profoundly  influenced  by  the  occurrence  of  infection; 
sapremia,  true  septicemia,  or  even  pyemia  sometimes  develops. 


DIAGNOSTIC  FEATURES  OF  SARCOMA  AND  CARCINOMA.^ 


Sarcoma. 

1.  Origin.  Entirely  mesoblastic. 

(Connective-tissue  type.) 

2.  Stroma.  Intercellular.       Rarel}^  forms 

alveoli. 


Carcinoma. 

Epiblastic  and  hypoblastic. 
(Epithelial-tissue  tyjje.) 

Vascular  connective  tissue, 
which  surrounds  and  forms 
the  walls  of  the  alveoli; 
these  communicate  with  one 
another,  and  contain  masses 
of  epithelial  cells.  . 

'  After  Woodhead;  modified  and  extended. 


TUMORS. 


363 


,V  Cells. 


4.  Intercellular 

substance. 

5.  Vessels. 


6.  Spreads. 


7.   Secondary 
changes. 

S.  Growth. 

Q.  Site. 


10.  Heredity 

11.  Capsule. 


12.  Fat. 
13-  Age. 

14.  Injury. 


Sarcoma. 

Granulation  tissue  or  embry- 
onic connective-tissue  cells; 
shape  and  size  vary. 

May  be  present. 

Embryonic  in  character. 
They  are  in  direct  contact 
with,  or  may  be  formed 
by,  the  special  cells,  slightly 
modified,  of  which  the  tu- 
mor is  composed. 

Primarily  and  secondarily  by 
blood-vessels,  rarclv  by  the 
h-mphatics. 


Chondroid,  osseous,  calcific, 
and  pigmentary  changes 
frec^uent. 

Not  m  variably  continuous. 
Likely  to  be  interrupted. 

Primarily  in  deep  structures; 
always  from  connective 
tissue. 

Seldom  hereditary. 

Primarily,  pseudoencapsu- 
lated;  later,  infiltrates  the 
surrounding  tissue. 

Rarely,  if  ever,  contains  fat. 

Occurs  most  frequently  be- 
fore middle  life. 

Not  uncommonly  follows  in- 
jury, such  as  trauma. 


Carcinoma. 

Epithelial  cells  ccmtaincd  with- 
in alveoli;  shape  and  size 
vary. 

Absent,  or  merely  fluid. 

Well  developed;  entirely  con- 
tained within  the  connective- 
tissue  stroma,  and  supported 
by  the  walls  of  the  alveoli. 
Seldom  in  contact  with  the 
cells. 

Primarily  h\  lymphatics,  ex- 
cept in  the  later  stapes,  when 
it  may  also  spread  by  blood- 
vessels, in  which  case  it 
spreads  with  very  great 
rapidity.  Secondarily  by 
blood-vessels. 

Very  rare. 


Rapid.     Continuous. 

Primarily  in  superficial  struc- 
tures or  glands;  always  from 
epithelium. 

May  be  hereditary. 

Xever  encapsulated. 


Nearly  always  contains  fat. 

Most  frequent  after  middle 
life. 

Rarely,  a  history  of  trauma, 
but  may  follow  prolonged 
rrritation.  Especially  is  this 
true  of  the  superficial  forms. 


MIXED  TUMORS. 
Tumors  Composed  of  Both  Types  of  Tissue. 

Teratoma.* — This  rare  variety  of  tumor  is  composed  of  epithelial 
and  connective-tissue  types  (adult  and  embr}-onic),  and  originates  in 
rudiments  derived  froni  the  three  layers  of  the  blastoderm  (ectoderm, 
mesoderm,  and  endoderm).  Teratomata  are  congenital  tumors,  usually 
occurring  in  the  sacral  region  (coccygeal  tumors),  the  head  and  neck, 
mediastinum,  or  the  abdominal  cavity;  they  are  occasionally  observed 
in  the  kidnev,  ovar>',  and  testicle. 

They  may  be  due  to  inclusion  and  imperfect  development  of  one 
fetus  within  another,  or  to  abnormal  proliferative  changes  in  the  tissues 
of  one  fetus.     They  van,-  in  size — may  be  small  at  birth,  and  may 

•  The  most  important  literature  on  the  subject  can  be  found  in.  or  traced  from. 

the  following  articles:    Steinert,    "Virchow's  Arch."    Nov.   4,    iqo.v     Schla?:en- 
haufer.  "Wien.  Win.  Woch.."  1902,  p.  571.     T6denat. 
1903,  p.  514.     Chiari,  •'Ccntralbl.  f.  allg.  Path.  u.  t  ' 
9S7.     Henderson,   "Jour.  Amer.   Med.  Assoc.,"  J' 
"Deut.  med.  Woch.."  1903.  No.  35.     Fer6.  "Soc. 
See  also  references  given  under  Dermoid  Cysts. 


Revue  de  Chir. 


Nov 


364 


GENERAL  PATHOLOGY. 


remain  stationary  or  continue  to  develop.  As  evidence  of  fetal  inclu- 
sion, the  tumor  mass  may  contain  structures  definitely  suggestive  of 
organs.  Teratomata  are  frequently  cystic ;  they  sometimes  recur  after 
what  was  believed  to  have  been   complete  removal;      such  recurring 

tumors  are  thought  by 
some  to  possess  a  sar- 
comatous  element. 
Dermoid  cysts  are,  bv 
some  writers,  classed 
with  the  teratomata.^ 

Chorioepithelioma  - 
( Deciduoma  nialignum , 
Syncytioma,  Sarcoma  de- 
ciduo-cellulare ,  malig- 
nant placental  polyp, 
etc.)  is  a  peculiar  tumor 
the  exact  oncologic 
position  of  which  has 
not  been  determined  to 
the  satisfaction  of  all 
observers.  It  has  been 
regarded  as  a  sarcoma 
and  strongly  resembles 
tumors  of  that  group. 
Most  authorities  recog- 
nize the  impossibility  of 
definitely  assigning  the 
neoplasm  to  any  recog- 
nized class,  and  some 
hold  that  a  number  of 
tumors  are  at  present  in- 
cluded under  the  one 
name  and  really  consti- 
tute a  group.  The  pri- 
mary neoplasm  is  prac- 
tically always  in  the 
uterus  and  usually  fol- 
lows labor  or  abortion. 
The  tumor  gives  rise  to 
extensive  metastases  bv 
the  blood;  secondary 
growths  are  particularly 
prone  to  involve  the 
lungs,  brain,  and  kid- 
neys. The  primary  and 
metastatic  masses  are 
exceedingly  vascular 
and  composed  of  large 
blood-sinuses  containing  structures  resembling  the  chorionic   villi,  and 

^  See  Dermoid  Cysts. 

^  The  important  literature  on  the  subject  is  quoted  bv  Bland,  "Jour.  Amer. 
Med.  Assoc,"  June  10,  1905,  p.  1827;  bibliograph}-. 


Fig.  210. — Teratoma. 

Section  of  cyst  wall,  case  of  teratoma  of  the  sacrum,  operated  upon  Ijy 

Prof.   \\'.   W.   Keen.     Xote  the  resemblance   to   the   wall   of  a 

bronchus.    A .  Cylindric  ciliated  epithelium.    B.  B.  Glands  lined 

by  low  columnar  epithelium.      C.  Blood-vessel.     D.  Cartilage. 


TUMORS. 


365 


KlG.    211. —  li.KAI     UA    'l      I'lSTICLE. 

Matruc  composed  of  myxomatous  and  collagenous  tissues;   also  containing  smooth'musclc  bundles  ard  on  the  ex- 
treme left  an  island  of  fetal  cartilage.     The  cysts  ai^  lined  by  columnar  epithelium  which  in  places  is  ciliated.     - 


D 


A  - 


Fic.  3  I 
Case  of  Dr.  Montgomery's,  studio!  by  I)r.  Bland,  in  iii< 
moved  from  its  centnd  pinion.     .-I,  A.  A.     I-irgc  w.i: 
villi  showing  marked  aisturbancc  in  t  jnghans'  cell 


?66 


GENERAL  PATHOLOGY. 


particularly  characteristic  are  the  large  multinucleated  protoplasmic 
masses  similar  to  the  syncytial  cells.  (See  Fig.  212.)  Chorioepithelio- 
mata  vary  widely  in  malignancy;  some  growths  prove  fatal  in  a  few 
weeks,  while,  in  other  cases,  partial  removal  is  followed  by  complete 
recovery.  In  the  case  reported  by  Noble  it  was  recognized  at  operation 
that  definite  neoplastic  tissue  was  left  behind;  the  patient,  however, 
recovered.  Some  writers  speak  of  chorioepithelioma  malignum  and 
chorioepithelioma  benignum  as  distinct  neoplasms 


TUMORS. 

(Those  printed  in  italics  are  malignant.) 


r  Epithelial    (Epiblast 
I        and  Hypoblast) 


r  Neoplasms 


C  Adult     (Typical 
I        Benign) 


Embryonic 
(Atypical, 
Malignant) 


Connective  tissue 
(Mesoblast) 


L  Embryonic 
(Atypical, 
Malignant) 


I    Papilloma  \ 

{ 

f 


Adenoma 

"1 

Neuroma ' 
L  Glioma 


Skin  warts. 

Villous  warts. 

Intracystic  warts. 

Acinous. 

Tubular. 

Ganglionic  neuroma. 
<    Myehnic  neuroma. 
I  Amyelinic  neuroma. 


Carcinoma,   or   j 
Cancer 


r  Epithel- 


i  Squamous. 
<  Tubulated. 
(  Cylindric. 
( Scirrhus. 


r  Adult      (Typical 
I        or    Benign) 


I'  Lipoma 
Chondroma 
Osteoma 

Fibroma 

!Myoma 

Angioma 


Ly  m  ph- 

oma  (?). 
Myxoma. 


f  Sarcoma 


[_  Glandular    -j  Encepha- 
(     laid. 
(Colloid, 
Mucoid, 
Melan- 
otic.) 
J    Simple. 
\  Fibrous. 

r    Eburnated. 
-     Compact. 
I   Spongy. 

Si-P'^  {fo^ff 

Fibroma  Molluscum. 

Keloid. 

Leiomyoma  (Unstriped). 

Rhabdomyoma  (Striped). 

Hemangio-    (Simple. 

ma  (Blood--  Cavernous. 

vessels)         tPle.xiform. 
Lymphangioma 
( Lym  ph- vessels) . 


r  Round-cell    {^Zl 
I    Spi-dle-cell  {^j;^[j- 
Myeloid. 


Mi.xed-ccll. 
L  Alveolar 

(.Melanotic. 
Cystic,  etc.). 


Cysts 


Mixed, Teratoma. 

(Both  Epithelial 
and  Connective- 
tissue.) 

r  (i)  Retention  (occluded  excretory  ducts). 

(2)   Exudation  (accumulations  in  closed  cavities). 

I     (3)   Cystomata  (new  formation). 

]    (4)  Extravasation  (those  forming  from  extravasations). 

I    (s)  Dermoid    (congenital   and  due  to  inversion  of   the  cutis  and  to  imperfectly  closed 

I  fetal  clefts). 

1    (6)  Parasitic  (due  to  animal  parasites). 

I    (7)  Cysts  resulting  from  necrotic  and  degenerative  changes. 


*  See  foot-note,  p.  320. 


TUMORS  367 


CYSTS. 


A  cyst  consists  of  a  connective-tissue  membrane  or  supporting  wall 
lined  by  epithelium  or  endothelium,  and  forming  a  cavity  the  contents 
of  which  may  be  fluid  or  semitluiil,  uniform  in  composition,  or  made 
up  of  a  mixture  of  similar  or  dissimilar  substances. 

When  the  wall  of  the  cyst  is  passive  and  inlluenced  by  the  retained 
or  extravasated  contents  in  a  mechanical  way  only,  the  cyst  is  said 
to  be  simple  or  u>iilociilar.  When  several  simple  cysts  occur  together, 
all  arising  from  the  same  cause,  and  identical  in  structure,  they  are 
called  multiple  cysts.  When  one  cyst  springs  from  the  wall  of  another 
and  thus  gives  rise  to  a  second  or  a  third  cyst,  the  process  resembling 
proliferation,  the  resulting  cysts  are  known  as  proliferous  cysts;  the 
cyst  walls  may  be  destroyed  by  pressure  (reciprocal),  and  thereby 
many  of  the  cyst  cavities  communicate.  When  the  cysts  remain  dis- 
tinct, they  are  spoken  of  as  multilocular.  When  the  cysts  communicate, 
they  are  sometimes  said  to  be  caveruous.  When  the  lining  membrane 
of  the  cyst  develops  papillomatous  masses,  the  process  is  called  pap- 
uliferous. 

Classified  by  the  cause  and  process  of  development  cysts  may  be 
divided  into:  (i)  Retention  cysts;.  (2)  exudation  cysts;  (3)  cystomata; 
(4)  extravasation  cysts;  (5)  dermoid  cysts;  (6)  parasitic  cysts;  (7)  cysts 
resulting  from  necrotic  and  degenerative  chajiges  in  solid  tissues. 

1.  Retention  Cysts. — These  include  all  cysts  due  to  occlusion  of 
excretorv  ducts  of  glands  with  accumulation  of  glandular  secretion 
and  exudative  fluids  in  the  closed  cavity  resulting  from  obstruction 
of  the  passage  by  which,  normally,  evacuation  occurs.  Among  the 
most  common  are:  sebaceous  cysts  (wens);  mucous  cysts;  salivar}' 
cysts  (ranulae);  milk  cysts  (galactoceles);  seminal  cysts  (true  spermato- 
celes); nephric  cysts  (see  Cysts  of  the  Kidney);  cysts  of  the  gall- 
bladder or  biliary  passages;    pancreatic  cysts  (pancreatic  ranulae),  etc. 

The  wall  of  such  cysts  is  composed  of  condensed  and  thickened 
connective  tissue,  and  the  lining  cells  are  epithelial.  The  contents 
are  derived  from  the  functional  activity  of  the  gland  structure,  altered 
by  absorption  of  a  part  of  the  fluid  and  by  the  degenerative  changes 
that  the  cellular  elements  of  the  cyst  wall  may  have  undergone.  When 
the  duct  obstruction  first  occurs,  the  accumulating  fluid  is  a  product 
of  secretory  activity  of  the  gland;  if  the  obstruction  be  complete, 
normal  secretion  soon  ceases,  the  gland  undergoes  degenerative  and 
fibrous  changes,  and  irritation  gives  rise  to  inflammation  of  the  cyst 
wall  and  the  formation  of  an  exudate  which  rapidly  replaces  the  fluid 
at  first  accumulated.  The  change  in  the  physical  and  chemic  characters 
of  the  cvst  contents  is  facilitated  by  osmosis.  Not  uncommonly  cysts 
of  this  class  eventually  contain  none  of  the  materials  characteristic  of 
the  gland  in,  or  from  which  they  arise:  e.  g.,  the  fluid  found  in  the 
kidney  in  hydronephrosis  may  contain  no  body  characteristic  of  the 
renal  secretion.     (See  Hydronephrosis.) 

2.  Exudation  Cysts. — These  embrace  cysts  arising  from  accumula- 
tion in  closed  cavities  not  supplied  by  any  excretor>'  ducts  or  analogous 
structures.  Such  cysts  are  typified  in  the  accumulations  in  bursa?, 
tendon-sheaths,  the  tunica  vaginalis  testis  (hydrocele),  canal  of  Nuck, 
etc.     The  cyst  wall  is  formed  bv  thickened  connective-tissue  membrane 


368  GENERAL  PATHOLOGY. 

lined  with  endothelium;  the  sac  or  wall  may  be  calcareous,  cartilaginous, 
fibroid,  chondroid,  or  even  osteoid.  The  contents  are  usually  a  clear, 
limpid,  serum-like  liquid,  but  the  fluid  may  be  viscid  or  semigelatinous, 
or  the  cyst  may  contain  solid  bodies  resulting  from  changes  in  the  wall 
and  desquamation  or  exfoliation  into  the  cavity. 

3.  Cystoma^  (hygroma  or  hydroma)  is  a  cyst  resembling  the  preceding, 
except  that  it  is  of  new  formation.  The  wall  is  of  mesoblastic  origin, 
lined  by  a  flattened  layer  of  connective-tissue  cells  (endothelium). 
The  contained  fluid  is  usually  clear,  straw-colored,  slightlv  albuminous, 
and  of  low  specific  gravity;  rarely,  the  fluid  may  be  colored,  cloudy, 
or,  as  a  result  of  hemorrhage,  grumous  and  possessing  a  dark,  chocolate 
color.  As  to  site,  cystomata  are  most  frequent  in  the  neck  (hvdrocele 
of  the  neck)  and  in  the  axillae  (hydroceles  of  the  axillae) ;  although  infre- 
quent, they  have  been  observed  in  the  subcutaneous  structures  else- 
where— back,  belly,  and  even  the  extremities.  Ba-  reason  of  their 
being  most  commonly  congenital,  occasionally  associated  with  macro- 
glossia,  and  on  account  of  their  close  resemblance  to  the  dilated  lymph- 
spaces  of  the  frog,  it  is  believed  by  many  that  they  arise  from  dilatation 
of  the  lymph-spaces;  this  view,  if  correct,  would  place  them  with  the 
cavernous  lymph  angiomata  (p.  347). 

On  three  occasions  the  writer  has  seen  cystoma  of  the  liver;  thev 
were  presumably  congenital,  and  had  been  mistaken  for  sarcomata. 
One  of  the  patients  died  from  hemorrhage  into  the  cyst,  and  the  others 
from  intercurrent  maladies.  The  three  were  children,  aged  three,  five, 
and  six  years  respectively.  It  is  not  uncommon  to  find  these  cysts 
cavernous,  with  cavities  of  various  sizes  communicating  with  one  an- 
other through  one  central  space.  The  rule,  as  stated,  that  the  specific 
gravity  of  the  contained  fluid  is  low.  has  occasional  exceptions,  as,  in 
rare  instances,  the  fluid  may  be  as  dense  as  the  white  of  an  egg,  and 
so  tenacious  that  it  will  not  flow  through  an  ordinary  cannula  intro- 
duced in  tapping. 

The  most  frequent  site  of  a  cystoma  is  in  the  ovary.  Such  tumors 
may  be  unilocular, — that  is,  made  up  of  a  single  cyst  cavitv, — or  thev 
may  be  multilocular.  The  multilocular  ovarian  cystomata  usuallv 
contain  one,  two,  or  more  large  cysts  and  numerous  smaller  cavities. 
As  a  result  of  reciprocal  pressure,  there  may  be  more  or  less  destruction 
of  the  septa,  and  numerous  loculi  may  communicate  with  one  another, 
forming  a  cavernous  cyst,  within  the  cavities  of  which  the  fluid  is  lodged. 
Certain  of  the  ovarian  cystomata  develop  papillary  ingro\\^hs,  projecting 
from  the  inner  membrane  of  the  cyst  wall  as  wart-like  excrescences, 
which  may  be  small  or  scarcely  recognizable,  or,  on  the  other  hand. 
may  form  large  accumulations  within  the  cyst  cavity.  As  a  rule,  papillif- 
erous  CA'stomata  are  multilocular;  less  commonly  they  are  unilocular. 
The  lining  membrane  of  ovarian  cystoma  is  usually  composed  of  colum- 
nar epithelium,  which  in  some  cases  may  be  of  the  tall  variety.  Cilia- 
tion  is  rare.  External  to  the  epithelial  stratum  the  wall  is  composed 
of  fibrous  connective  tissue,  which  may  contain  myxomatous  elements, 
and  at  times  masses  of  gland  tissue.  In  the  presence  of  the  latter 
element  the  tumors  are  called  cystadenomata,  and  are  usually  papuliferous. 
Cystomata  sometimes  become  infected  and  suppurate;  usuallv  this 
accident  is  disastrous,  most  of  the  patients  dying.  Werth,  Pitha,  Wal- 
'  Smith,  "Medicine,"  September,   1903,  p.  662. 


TUMt)RS.  369 

gren,-  anil  Zantchcnto'  have  reported  su])|)uralif)n  of  ovarian  cysts 
occurring  as  complications  of  typhoid  fever;  in  ni(jst  of  the  recorded 
instances  the  cysts  were  demioids,  but  the  ordinary  type  of  ovarian 
cvstoma  may  be  similarly  affected. 

As  a  rule,  ovarian  cystoma  is  the  largest  cyst  observed  in  tlie 
human  body.  Dr.  Elizabeth  Reifsnyder  has  reported  the  removal  of 
an  ovarian  cyst  containing  85  htcrs  (ai)proximately  88  quarts)  of  fluid 
and  weighing  83  kilos  (lOg  pounds);  the  patient  weighed  but  38  kilos 
(77  pounds).  The  tumor  was  unilocular,  the  empty  sac  weighing  .^2 
kilos  (6^^  pounds). 

4.  Extravasation  Cysts.  —This  variety  of  cyst  is  formed  around  dis- 
tended or  ruptured  vessels,  or  in  areas  of  henKjrrhage,  and  may  occur  in 
any  tissue.  Hojiatocclc ,  or  any  form  of  sani:^iiincoHs  cyst,  is  properly 
classed  with  this  group.  The  cyst  wall  is  usually  thin,  and  its  inner  sur- 
face smooth;  but  the  reverse  may  be  true.  In  rare  cases  the  internal 
surface  of  the  cyst  wall  is  fasciculated.  The  inner  stratum  of  the 
connective-tissue  investment  of  the  cyst  is  first  formed  by  the  dis- 
sociated connective  tissues;  later  these  may  be  replaced  by  an  en- 
dothelial covering.  Rudolf-  fully  describes  the  hematomata  that  occur 
in  the  mesentery  as  a  result  of  direct  injury  to  the  abdominal  wall  or 
indirect  trauma,  as  by  falls;  these  cases  usually  terminate  fatally.  As 
a  result  of  injurv  during  birth  hematomata  are  sometimes  seen  in 
the  sternocleidomastoid  muscle  of  the  new-born.  By  some  writers 
the  intrafollicular  and  intraparenchymatous  hemorrhages  in  the  ovarv' 
(ovarian  apoplexy)  are  classed  with  the  hematomata.  As  a  result  of 
injurv,  or  disease  of  the  vessels,  meningeal  hemorrhage  sometimes 
gives  rise  to  hematoma,  which  may  be  subdural  or  extradural.  A 
special  form  of  this  condition,  called  hemorrhagic  pachymeningitis,  is 
discussed  in  the  chapter  on  diseases  of  the  Nervous  System.  Cysts 
occasionallv  occur  through  the  extravasation  of  fluids  other  than  blood; 
the  accumulation  of  urine  in  the  perineum,  following  rupture  of  the 
urethra,  is  a  type  of  such  cysts. 

5.  Dermoid  cysts  are  always  of  congenital  origin,  and  arise  as  the 
result  of  cutaneous  inclusion,  or  in  consequence  of  the  inclusion  of  a 
blighted  ovum.  The  wall  may  contain  all  the  elements  of  the  cutis, 
may  be  thick  or  thin,  and  not  uncommonly  shows  a  slight  gro\nh  of 
hair;  the  cells  lining  the  interior  of  the  sac  are,  of  course,  epithelial. 
The  contents  are  usually  sebaceous  matter  and  a  varying  amount  of 
hair;  occasionally,  teeth  are  found.  When  situated  in  the  ovary,  tes- 
ticle, brain,  eve,  throat, or  abdominal  cavity, developing  bone  or  cartilage 
may  be  contained  within  the  cyst  cavity;  these  distinctly  connective- 
tissue  products  indicate  the  possibility  of  such  cysts  arising  from  fetal 
inclusion.  Occasionally,  dermoid  cysts  contain  fat  the  melting-point  of 
which  is  below  the  normal  temperature  of  the  l)ody.  The  author  exam- 
ined one  such  cyst.  The  tumor  had  evidently  developed  in  the  region 
of  the  ovarv;  the  wall  was  so  dense  and  calcareous  that  a  saw  was  neces- 
sarv  to  open  the  mass.  The  temjjcrature  of  the  body  was  still  compara- 
tivelv  high,  and  the  oily,  fluid  contents,  which  flowed  from  the  interior 
of  the  cvst.  immediately  congealed  on  coming  in  contact  with  cold  water. 
A  ';imil''ir  ttmior  of  the  ovary  has  been  described  by  Thoma.     Dermoids 

'  "  Rousski  Vratch, "   1003.  No-  30- 

»  "  Beit  rase  z    klin.  Chir   "  ^''ii     V-    - 


37©  GENERAL    PATHOLOGY. 

containing  distinct  connective-tissue  bodies,  such  as  cartilage  and  bone, 
are  termed  compound  dermoids,  thereby  distinguishing  them  from  der- 
moids containing  no  connective-tissue  elements;  the  latter  are  called 
simple  dermoids.  The  most  common  sites  are  near  the  orbit,  the  root 
of  the  nose,  the  angle  of  the  jaw,  the  floor  of  the  mouth,  around  the 
sheath  of  the  carotid  vessels,  near  the  anus,  and  the  sacrococcygeal  and 
ovarian  regions.  There  can  be  no  doubt  that  most  of  the  dermoids 
occurring  in  the  body  cavity,  and  sacral  and  perineal  regions,  belong 
with  the  teratomata.  (See  page  363.)  Following  the  observations  of 
Wilms,  the  tendency  has  been  to  call  such  tumors  embryomata.^  When 
two  layers  of  the  blastoderm  are  represented  by  structures  in  the  growth 
the  term  bidermoma  has  been  applied;  when  three  layers  are  present, 
tridermoma.  Sometimes  these  masses  contain  fully  formed  organs, 
such  as  a  jaw,  finger  or  hand,  part  of  the  thyroid  gland,  etc. 

Closely  related  to  the  dermoid  cysts  but  entirely  distinct  from  them 
are  the  so-called  traumatic  dermoids  which  develop  in  wounds.  These 
cysts  are  due  to  the  inclusion  of  the  epithelial  layers  of  the  skin  or  mucous 
membrane  within  the  healed  wound.     Klar  calls  them  epidermoids.^ 

6.  Parasitic  Cysts.— When  any  animal  organism,  capable  of  surviving 
in  the  tissues,  gains  ingress,  a  cyst  is  likely  to  ensue;  some  such  parasites 
inevitably  give  rise  to  cysts,  others  not  always.  Trichince,  when  settled, 
develop  a  small  cyst  that  rapidly  becomes  calcareous.  (See  p.  204.) 
Coccidia  invading  the  liver  induce  a  similar  condition.  (See  p.  184.) 
The  most  important  parasitic  cyst  in  man,  so  far  as  our  present  knowledge 
goes,  is  the  hydatid.  This  cyst  arises  as  the  result  of  the  lodgment  of  the 
larvae  of  the  Taenia  echinococcus  in  the  tissues.  The  embryo  is  first  con- 
verted into  a  cyst  containing  a  clear  fluid.  The  wall  possesses  two  layers 
of  its  own,  to  which  is  added  a  layer  resulting  from  the  reaction  of  the 
surrounding  elements.  From  the  inner  layer  of  the  cyst — the  endocyst — 
buds  are  developed  that  give  rise  to  daughter  cysts;  other  cysts 
develop  in  a  similar  way  from  the  daughter  cysts,  and  constitute  what 
are  known  as  granddaughter  cysts.  These  cysts  are,  therefore,  pro- 
liferative. The  fluid  of  the  cyst  is  usually  nonalbuminous,  slightly 
saline,  and  clear;  its  specific  gravity  is  less  than  loio,  and  it  may  contain 
sugar.  Such  cysts  are  likely  to  become  inflamed,  to  suppurate,  or  to 
rupture,  all  of  which  terminations  are  unfavorable.  If  the  parasite  dies, 
the  cyst  may  inspissate.  It  is  not  an  exceptional  thing  to  find  these 
inspissated  cysts  in  the  liver;  the  contents  are  usually  putty -like,  occa- 
sionally crumbly,  and  frequently  contain  the  hooklets.  Inspissation 
represents  a  cure,  but,  unfortunately,  other  terminations  may  occur;  the 
cyst  may  rupture  into  a  closed  cavity,  as  one  of  the  serous  cavities;  rup- 
ture externally  or  into  a  bronchus  or  other  hollow  viscus  occurs.  A 
most  dreaded  termination  is  suppuration.  (For  consideration  of  the 
forms  of  hydatid  cysts,  diagnosis,  and  demonstration  of  hooklets,  and 
for  illustrations,  see  pp.  198  to  201.) 

Cysticercus  Cellulosae,  the  larval  form  of  the  Taenia  solium,   gives 

'  See  Clark,  "Progressive  Medicine,"  June,  1902,  p.  223.  Anspach,  "Proceed, 
of  Path.  Soc.  of  Phila.,"  Nov.,  1903,  p.  209.  Lecene,  "Annal  de  Gynecol,  et 
d'Obst.,"  Jan.,  1904,  p.  14.  Hue,  "Rev.  Med.  de  Normandie,"  July  25,  1904. 
Lejars,  "La  Sem.  Med.,"  Sept.  21,  1904. 

^"Miinch.  med.  Woch.,"  April  19,  1904,  p.  705.  Also  Dujarier  and  Lecene, 
"La  Presse  Med.,"  April  16.  1904,  p.  241. 


TUMCJRS.  37  I 

rise  to  small  bladder-like  cysts,  which  may  l»e  widelv  distributed.  In 
the  pig,  the  usual  intermediary  host,  the  cysts  are  about  tlic  size  ot  a 
pea,  and  may  be  scattered  throughout  the  tissues,  producing  a  condition 
commonly  known  as  "measled"  or  "measley"  f)ork.  (See  p.  197.) 
In  man  the  cysts  occur  in  the  muscles,  brain,  and  spinal  cord;  occa- 
sionally, they  may  be  recognized  by  the  ophthalmologist  in  the  cham- 
bers of  the  eye. 

7.  Cysts  resulting  from  necrotic  and  degenerative  changes  in  solid  tis- 
sues include  the  cavities,  found  jjarticularly  in  ncoj^lasms,  and  brought 
al>out  by  hemorrhage,  liquefaction  necrosis,  and  other  forms  of  soften- 
ing'; the  cavities  containing  fluid,  sometimes  observed  in  solid  organs, 
such  as  the  spleen  and  brain,  and  due  to  the  imperfect  removal  of  lique- 
fied areas  resulting  from  infarction,  would  properly  be  classed  with  this 
group.  The  liquid  present  in  such  cysts  may  contain  altered  blood 
pigment  produced  by  hemolysis,  and  granular  matter  resulting  from 
cellular  disintegration. 

'  See  pai^e  2  ^o. 


CHAPTER    XIII. 
TEMPERATURE    CHANGES.^ 

INTOXICATIONS.     INFECTIONS. 

The  temperature  of  the  human  body  remains  practically  constant, 
or  about  so,  at  37°  C.  There  are  normally  for  each  individual  certain 
variations  above  or  below  the  mean  for  the  twenty-four  hours;  the 
maximum  fall,  in  health,  rarely  exceeds  0.5°  C,  and  is,  for  most  per- 
sons, always  at,  or  near,  the  same  hour  of  the  day;  the  same  is  true 
of  the  daily  rise,  so  that  between  the  daily  maximum  and  minimum 
there  is  commonly  about  1°  C.  of  fluctuation.  This  daily  curve  of  the 
temperature  follows  nearly  the  same  course  each  day,  so  that  the  maxi- 
mum is  reached  between  4  and  6  p.  m.,  and  the  minimum  between 
the  same  hours  a.  m.;  this  cycle  for  any  given  individual  is  nearly 
uniform,  but  no  two  persons  are  likely  to  have  identical  thermic  curves. 
The  following  table,  from  Thoma,  compiled  by  Jiirgensen  and  Lieber- 
meister,  indicates  the  usual  variations  in  body-temperature  at  different 
hours  in  the  day : 


Time  of  Observatiok. 


Temperature  in 
THE  Rectum. 
(^Jiirgensen.) 


Temperature  in 

the  .Axilla. 

{Liebermeister.) 


F. 

In  the  mornitig  in  bed (98° 

Before   breakfast (98.18° 

After  breakfast :      (98.36° 

In  the  forenoon, (98.8° 

Before   lunch, (99  18° 

After  lunch (99.36° 

In  the  afternoon, (99-5° 

Before  dinner, (99-7° 

After  dinner, (99.36° 

Before  going  to  bed, (98.8° 

(98.7° 
During  the  night, \  \      (98.36° 

(98.36° 


c. 

F. 

C. 

36.6° 

(97-8°  ) 

36.5° 

36.7° 

(98°       ) 

36.6° 

36.8° 

(98.7°  ) 

37° 

.S7-I" 

(99.18°) 

37-3° 

37-3° 

(99°       ) 

37-2° 

3  7-4^ 

(99.18°) 

37-.S° 

37-5° 

(99-36°) 

3  7-4° 

37-6° 

(99°       ) 

37-2° 

37-4° 

(98.8°   ) 

37-1° 

37-1° 

(98.36°) 

36.8- 

37^ 

(98°       ) 

36.6" 

36.8° 

(97.18°) 

36.2" 

36.8° 

(97.18°) 

36.2- 

The  hypotheses  and  theories  presumed  to  explain  the  mechanism 
of  temperature  regulation  are  based  upon  certain  well-established  facts. 
Heat,  representing  cellular  or  tissue  activity,  is  generated  within  the 
body  by  the  oxidation  of  supplied  or  stored  food,  or  of  the  tissues 
themselves,  is  distributed  largely  by  the  blood,  and  is  lost  chiefly  from 
the  skin  and  respiratory  mucous  membrane.  The  regulation  of  the 
body-temperature  must  be  through  means  addressed  to  one  of  three 
agencies:  heat  production,  distribution,  or  dissipation. 

^  A  very  full  bibliography  of  the  subject  is  given  by  Chantemesse  and  Podwys- 
sotsky,  "  Les  Processus  G^neraux,"  1905,  vol.  ii,  p.  500. 

372 


TRMPKRATURFi   CHAN'GES.  373 

Heat  production  occurs  in  every  organ  and  tissue,  but  the  greatest 
thermogenic  activity  is  manifested  in  tlie  muscles,  including  the  heart, 
and  in  the  large  glandular  viscera:  for  example,  the  liver.  The  greatest 
heat  production  occurs  in  the  voluntary  muscles,  including  those  of 
respiration.  The  heart  muscle  is  presumed  to  afford  a  considerable 
supply  of  heat  in  the  same  manner  as  the  other  muscles,  and,  in  addition, 
transmits  force,  which  is  indirectly  converted  into  heat  by  the  friction 
of  blood  against  the  cardiac  walls  and  also  against  the  walls  of  the 
arteries  and  capillaries,  through  the  resistance  of  which  the  blood- 
pressure  is  largely  maintained.  The  fact  that  the  blood  rises  in  tem- 
perature after  passing  through  the  liver  is  not  surprising  when  the 
remarkable  glandular  activity  of  that  organ  is  taken  into  consideration. 

The  distribution  of  the  blood  is  profoundly  influenced  by  the  nerves 
supplied  to  the  arterioles,  and,  as  the  dissipation  of  heat  is  largely 
dependent  upon  the  distribution  of  the  blood,  the  influence  of  vascular 
innervation  upon  heat  loss  is  one  of  the  most  important  elements  to 
be  estimated.  Exactly  what  determines  the  action  of  the  vasomotor 
ner^'es  in  the  regulation  of  temperature  is  one  of  the  unsolved  proV)lems 
in  normal  and  morbid  physiology.  It  would  appear  that  there  is  some- 
where a  center,  possibly  more  than  one.  that  presides  over  the  body- 
temperature  by  regulating  heat  dissipation  at  least,  if  not  its  pro- 
duction, but  probably  both.  The  theory  of  heat  regulation  by  the 
nerves  implies  a  heat-regulating  center  ( thermotactic  center),  with 
nerves  controlling  heat  production  (thermogenic  nerves),  nerves  con- 
trolling heat  dissipation  (thermolytic  nerves),  and,  possibly,  nerves 
that  influence  heat-producing  tissues  in  a  way  antagonistic  to  the 
thermogenic  nerves  (thermo-inhibitory  nerves).  This  complicated 
system  is  assumed  to  have  its  center  m  the  medulla;  this  center,  acted 
upon  by  certain  agents,  manifests  disturbance  through  the  fillers  of 
some  of  the  nerves  indicated.  In  addition  to  one  center,  or  possibly 
more,  in  the  brain  or  the  medulla,  there  may  be  in  the  cord,  or  even 
in  the  larger  ganglia,  subsidiary  centers  influencing  a  region,  or  regions, 
only.  "While  the  theor\'  of  heat  regulation  by  the  nervous  system  may 
be  considered  far  from  demonstrated,  the  facts  that  no  attempt  at 
heat  regulation  is  made  in  animals  possessing  an  indifferently  evolved 
nervous  system;  that  lesions  of  the  higher  evolved  ner\'ous  system 
are  followed  by  alterations  in  temperature  regulation;  and  that  the 
temperature,  both  normal  and  almormal,  may  at  times  be  influenced 
by  hypnosis,  would  each  seem  to  indicate  relations  between  heat  regu- 
lation and  the  nervous  system  that  can  not  Ite  ignored.  The  pro- 
duction of  heat  by  the  oxidation  of  food  and  of  tissue  elements,  the 
distriljution  of  the  heat  generated,  and  its  final  dissipation,  are  com- 
plicated phenomena  that,  with  our  existing  knowledge,  can  be  but 
imperfect Iv  rontem])latod. 

Hypothermia  (Subnormal  Temperature  .- A  temperature  below  the 
mean  normal  of  the  active  period  of  life  occurs  in  some  forms  of  anemia, 
and  in  myxedema,  chronic  heart-disease,  and  cancer,  follows  shock 
and  severe  hemorrhage,  is  present  in  some  forms  of  exhaustion  or 
advnamia.  and  frequently  succeeds  marked  elevations  of  temperature, 
particularly  if  prolonged;  thus,  after  typhoid  fever  and  pneumonia 
a  period  of  subnormal  temperature  is  often  seen.  Starvation  or  pro- 
longed exposure  to  low  temperatures,  or  the  two  combined,  may  give 


374  GEXERAL  PATHOLOGY. 

rise  to  a  reduction  in  the  body -temperature.  The  explanation  of  this 
condition  Hes  probably  in  the  lessened  heat  production,  although  in- 
stances occur — as  in  the  occasional  cases  of  great  cutaneous  activity 
after  hemorrhage  and  shock,  and  in  cases  of  exposure  to  extremely 
low  temperatures — in  which  more  heat  may  be  lost  than  normal;  such 
a  source  for  subnormal  temperature,  however,  is  not  common.  The 
reduction  of  temperature  may  also  be  caused  by  the  circulation  of 
certain  poisons  in  the  blood,  as  in  diabetes,  in  which  the  temperature 
may  sink  5°  C.  or  even  more.  In  this  condition  both  heat  production 
(thermogenesis)  and  heat  dissipation  (thermolysis)  are  probably  at 
fault,  the  control  and  equalization  of  the  two  by  the  thermotactic 
power  having  been  perverted  by  the  influence  of  a  noxious  agent  cir- 
culating in  the  blood. 

Pyrexia. — Under  certain  conditions  there  arises  a  chain  of  phenomena 
which  the  clinician  recognizes  as  fever.  There  is  disturbance  of  a  number 
of  functions:  appetite,  secretion  and  excretion,  the  circulation,  respira- 
tion, and,  in  many  cases,  the  central  nervous  system,  show  marked 
perturbation.  With  one  or  more  of  these  phenomena  there  occurs  the 
one  constant  element  of  fever — elevation-  of  temperature  (hyperthermia). 
In  moderate  cases  the  temperature  reached  may  not  exceed  39°  C; 
in  more  severe  cases  it  may  reach  41°  C,  and  in  grave  cases  may  go 
beyond  42°  C.     Temperatures  exceeding  55°  C.  have  been  observed.^ 

Causes. — Prolonged  exposure  of  a  warm-blooded  animal  to  a  temper- 
rature  in  excess  of  its  normal  commonly  induces  hyperthermia.  The 
rapidity  of  occurrence  and  the  degree  of  hyperthermia  are  dependent 
upon  the  height  of  the  temperature  to  which  the  animal  is  exposed,  and 
are  influenced  by  the  medium  through  which  the  heat  is  applied.  The 
temperature-rise  is  most  marked  if  the  animal  be  submerged  in  water; 
next  in  point  of  efficiency  is  air  containing  abundant  moisture,  while 
dry  air  is  least  efficient.  Absence  of  moisture  lessens  the  probability 
of  the  occurrence  of  hyperthermia,  and  individuals  may  be  subjected 
to  comparatively  high  temperatures  in  dry  air  and  yet  escape  heat- 
stroke. In  many  of  the  industries  laborers  are  exposed  for  a  varying 
period  of  time  to  comparatively  high  temperatures;  if  such  exposure 
be  prolonged  or  if  moisture  be  present,  heat-stroke  may  ensue. 

Hyperthermia  may  be  produced  by  diseases  or  injuries  of  the  central 
nervous  system;  puncture  of  the  corpus  striatum,  lesions  of  the  bulb, 
and  destruction  of  the  first  cerebral  convolution  may  be  followed  by 
hyperthermia.  Hale  White  has  recorded  two  cases  of  hemorrhage  into 
the  corpus  striatum  associated  with  a  rise  of  temperature,  most  marked 
on  the  opposite  side  of  the  body,  lasting  in  one  case  four  days,  and 
in  the  other,  twelve  days. 

There  can  be  no  doubt  that  the  most  important  causes  acting  in 
fever  production  are  bacteria  and  their  products.''-  That  the  germs  are 
not  the  essential  element  may  be  shown  by  the  production  of  artificial 
temperature-rises  by  the  injection  into  animals  of  filtered  and  also  of 
sterile  cultures  of  certain  bacteria.    The  introduction  of  preformed  poisons 

'See  Lord,  "Brit.  Med.  Jour.,"  Nov.  15,  1902,  p.  1578.  Bunbury,  "Brit. 
Med.  Jour.,"  July  25,  1903,  p.  193.  Oettinger,  "Colorado  Medicine,"  May,  1904. 
"Wood,  "Med.  Record,"  June  25,  1904,  p.  1041. 

'  See  bacterial  poisons,  p.  87. 


THMI'EkATL'RK    CHANCES.  ,^75 

into  the  svsieni  <;ivl's  rise  to  a  cliain  of  symptoms,  the  lonchtion  hein^ 
termed  an  intoxii\ition.^ 

The  t'el)rile  and  other  disturljances  asscxiatcd  witli  the  microbic 
intoxications  are  not  purely  the  outeome  of  hiboratory  exi)enmein,  ijul 
constitute  important  eUnical  phenomena.  The  symptoms  of  some  of 
the  infections  are  purely  the  evidence  of  intoxications;  in  diph- 
theria the  bacillus  may  be  limited,  even  in  fatal  cases,  to  ])rolifera- 
tion  on  the  surface  of  the  mucosa,  many  of  the  symptoms,  and  all  the 
lesions  occurring  elsewhere  than  at  the  point  of  growth,  result  from  the 
dissemination  of  the  toxin  through  the  lymphatics  and  its  distribution 
eventuallv  bv  the  blood.  A  simpler  example  of  pure  microbic  intoxi- 
cation, one  frequently  cited,  is  the  infection  of  a  blood-clot  in  the  uterus 
following  labor.  The  bacteria  generating  the  poison  in  the  blood-clot 
mav  never  gain  ingress  to  the  living  uterine  tissues,  much  less  to  the 
circulation,  but  the  products  of  microbic  life  pass,  by  absorption,  into 
the  blood,  through  which,  directly  or  indirectly,  they  induce  the  phenom- 
ena of  intoxication.  A  retained  blood-clot  between  the  flaps  in  a 
recent  amputation,  becoming  infected,  acts  in  a  similar  manner.  By 
reason  of  this  danger,  in  addition  to  its  mechanical  interference  with 
healing,  surgeons  recognize  the  necessity  of  avoiding  "dead  spaces" 
in  which  infection  may  be  favored  by  lessening  the  protective  influence 
of  living  tissues.  Commonly,  the  organisms  active  in  the  production 
of  bacterial  intoxications  are  pathogenic  in  the  true  sense  of  the  word. 
It  is  not  to  be  forgotten,  however,  that  bacteria  normally  unable  to 
infiltrate  living  tissues,  and  hence  properly  classified  with  nonpatho- 
genic organisms,  may  pullulate  in  dead  tissue,  and  may  elaborate 
poisons  the  absorption  of  which  gives  rise  to  grave  intoxications. 
The  intoxication  resulting  from  the  absorption  of  microbic  products  is 
known  as  septic  intoxication,  or  sapremia,  and  the  element  absorbed — 
the  bacterial  product — is  termed  pyrogenous.  A  peculiar  fact,  often 
observed,  is  that  in  the  brain  the  })roduris  of  bacterial  life  may  not  in- 
duce fever.  This  may  be  explained  in  a  number  of  ways.  Growing 
on  different  culture  media,  bacteria  produce  alkaloids  with  varying 
pvrogenous  activity,  and  in  the  brain-tissues  the  activity  or  character 
of  the  microbic  toxin,  by  reason  of  some  peculiarity  in  the  pabulum 
supplied,  may  be  changed;  the  very  fact  that  the  abscess  involves 
brain-tissue,  and  that  the  same  may  be  potential  in  controlling  tem- 
perature or  in  modifying  it,  may  make  the  accident  of  location  a  deter- 
mining factor  in  its  influence  on  body-temperature.  Again,  evidence 
is  not  wanting  to  show  that  dissemination  of  poisons  is  less  rapid  by  ab- 
sorption through  brain-ti.ssue,  and  this  may  in  part  explain  the  absence 
of  fever  in  some  cerel)ral  abscesses;  it  fails,  however,  to  ofTer  any  reason 
for  the  subnormal  temperature  at  times  observed. 

The  production  of  pyrogenous  substances  by  animal  parasites  is 
well  illustrated  bv  the  peculiar  febrile  phenomena  of  malaria.  Experi- 
mental research  into  the  exact  nature  of  the  fever-producing  body  elabo- 
rated by  such  organisms  as  the  malarial  parasite  has  not  afforded  any 
satisfactorv  conclusion,  nor  have  we  much  to  hope  for  in  this  direction 
until  it  becomes  po.ssible  to  study  the  parasite  in  artificial  culture.  It 
is  commonlv  believed  that  during  the  segmentation  of  the  protozoon 
there  is  elaborated  a  poison  that  brings  about  the  rise  in  temperature. 

•  See  p.  76. 


376  GENERAL  PATHOLOGY. 

While  such  a  view  may  be  satisfactory,  in  a  sense,  it  is  necessary  to 
remember  that  the  mere  destruction  of  blood-cells  may  bring  about 
fever,  and  when  it  is  recognized  that  in  malaria  this  process,  hemolysis, 
is  particularly  active,  we  can  not  ignore  the  possibility  of  its  bearing 
something  more  than  an  associated  relation  with  the  fever  present. 

Intoxications  arise,  however,  without  the  intervention  of  micro- 
organisms, either  animal  or  vegetable.  In  cocain-,  strychnin-,  and 
brucin-poisoning,  and  following  the  introduction  into  the  circulation 
of  certain  animal  poisons,  as  from  snake-bites,  stings  of  scorpions,  etc., 
typical  intoxications  occur.  Not  in  all  of  these  is  there  elevation  of 
temperature. 

In  addition  to  the  toxic  bodies  introduced  from  without, — such 
as  those  just  mentioned,  and  among  which  may  be  included  mussel- 
poisoning, — intoxications  may  arise  from  poison  generated  within  the 
body — direct  and  indirect  auto-intoxications.^  The  latter  include  en- 
terosepsis,  or  copremia,  an  intoxication  occurring  from  the  retention 
of  intestinal  contents,  as  in  chronic  constipation.  The  toxic  material 
here  is  not  wholly  a  microbic  product,  nor  is  it  entirely  the  result  of 
retention  and  absorption  of  noxious  agents  of  purely  animal  origin, 
but  is  far  more  complex,  including  poisons  derived  from  both  sources. 

There  is  another  source  of  fever-producing  or  pyrogenous  material 
in  tissue  dissolution  and  in  the  formation  of  certain  exudates;  the 
exudates  thrown  out  in  the  process  of  repair,  during  the  formation  of 
blood-clots, — as  around  fractured  bones  and  under  similar  conditions, — 
contain  some  agent  that,  by  absorption,  produces  elevation  of  tempera- 
ture. The  chemistry  and  even  the  identity  of  the  body  is  still  a  matter 
for  speculation.  Brieger  noted  the  constant  association  of  fever  and 
fibrin  formation,  and  surmised  that  both  depended  upon  the  presence  of 
the  ferment  presumed  to  cause  the  separation  of  the  liquor  sanguinis 
into  fibrin  and  serum;  this  view  has  been  generally  accepted.  But 
numerous  observations  go  to  show  that  disintegration  of  other  sub- 
stances than  the  plasma  can  be  attended  by  the  liberation  of  disinte- 
grative endogenous  poisons.  The  rise  of  temperature  that  follows  a 
surgical  operation,  the  fracture  of  a  bone,  or  an  interstitial  hemorrhage 
is  presumed  to  be  due  to  pyrogenous  materials  produced  in  the  way  just 
indicated.  These  fevers — surgical  aseptic  fevers — are  not  usually 
classed  with  the  intoxications,  although  it  is  evident  that  they  are 
essentially  of  that  nature. 

Local  Infections. — In  sapremia  the  poisons  generated  by  the  bac- 
teria are  elaborated  outside  of  living  tissues,  and  in  septicemia  the  toxic 
bodies  are  derived  from  bacteria  in  the  blood.  Intermediate  between 
these  are  the  local  tissue  infections,  in  which  the  bacteria  invade  living 
tissue,  from  which  the  microbic  poisons  are  absorbed  into  the  circu- 
lation, either  directly,  through  the  capillary  walls,  or  indirectly,  by  the 
lymphatics.  In  diphtheria  the  bacteria  may  reside  on  the  surface 
of  the  mucosa  only,  the  toxins  disseminating  beyond  and  inducing 
necrosis, — more  dead  tissue, — into  which  the  bacteria  grow.  In  some 
cases,  however,  the  germs  pass  the  dead  membrane  and  infiltrate  the 
living  tissues;  there  is  then  a  local  infection  of  living  tissues  as  well 
as  a  growth  in  the  dead,  or  necrotic,  adjacent  structures.  Erysipelas, 
abscess  formation,  the  initial  lesion  of  anthrax,  and,  under  similar  con- 
^  See  classification  of  poisons  and  intoxications,  p.  77. 


TEMPERATURE   CHANGES.  ;-' 

ditions,  main-  infections,  are  in  part — i)rimarily,  at  least —but  local 
infections,  with  dissemination  or  absorption  of  the  microbic  products 
giving  rise  to  the  phenomena  of  an  intoxication,  the  blood  escaping 
actual  invasion  by  the  bacteria.  The  local  infections,  with  systemic 
symptoms  due  to  the  absorption  of  toxins  produced  in  the  living  tissues, 
stand  intermediate  between  pure  intoxications,  such  as  sapremia.  and 
the  mycoses  of  the  blood. 

Any  infection,  whether  localized  or  widely  diffused,  may  be  simple  : 
that  is,  single,  or  due  to  but  one  germ,  as  a  pure  or  simple  infection  by 
the  streptococcus  of  erysipelas.  A  simple  or  single  infection  may  be 
followed  by  the  introduction  of  a  second  germ;  the  additional  infection 
is  known  as  a  secondary  infection.  As  an  example  of  the  last-named 
condition  may  lie  mentioned  the  infection  of  a  tuberculous  area  with 
an  organism  of  supjjuration.  A  secondary  infection  may  be  followed 
by  a  tertiary  infection,  and  so  on.  Again,  a  number  of  infections  may 
occur,  so  far  as  we  can  determine,  at  one  time;  the  process  is  then  said 
to  be  mixed  infection  or  concurrent  infections.  It  is  interesting  to 
note  that  in  the  mixed  and  secondary  infections  it  is  not  necessary  that 
all  of  the  bacteria  present  should  belong  to  the  pathogenic  class.  If 
one  of  the  microbes  be  disease-producing  and  lead  to  tissue  necrosis, 
the  secondary  infection  may  be  by  a  saprophyte  living  upon  the  dead 
tissue  resulting  from  the  necrotic  processes  induced  by  the  pathogenic 
organism.  As  a  rule,  mixed  and  secondary  infections  are  more  grave 
than  simple  infections,  because  the  additional  ferments  produced  by  the 
second  genn  can  but  intensify  the  dangers  to  which  the  patient  is  sub- 
jected. 

The  fact  that  nonpathogenic  bacteria  live  and  produce  noxious 
elements  in  the  necrotic  tissues  produced  by  pathogenic  bacteria  renders 
it  possible  to  appreciate  how  dead  tissue,  or  tissue  with  its  protective 
powers  in  a  state  of  abeyance,  as  after  extensive  bruising  or  laceration, 
may  permit  the  growth  of  bacteria  that,  in  less  injured  tissues  or  in 
healthy  structures,  would  immediately  succumb  to  the  protective  powers 
of  the  animal.  For  these  reasons  injured  structures  and  tissues  with 
greatly  reduced  nutrition  may  need  a  protection  from  infection  not 
demanded  by  healthy  tissues. 

Bacteremia.  Mycoses  of  the  Blood. — In  this  condition  the  bacteria 
multiply  in  the  circulating  blood,  in  which  their  products  are  gener- 
ated. The  intensity  of  the  septic  phenomena  is  augmented  by  the 
greater  production  of  the  poison,  and.  not  having  even  the  barrier 
of  protection  afforded  l^y  the  necessity  of  osmosis  or  absorption, 
they  are  enabled  to  engender  lesions  not  ])resumed  to  occur — at 
least,  not  to  the  same  extent — in  either  sa])remia  or  local  infection. 
The  path  of  infection'  may,  as  in  surgical  sepsis  and  puerperal  cases, 
be  self-evident.  In  othe-  instances  it  is  impossible  to  determine  exactly 
by  what  route  the  infecting  organism  entered  the  circulation;  to  this 
latter  group  Leube  gave  the  name  cryptogenic  sepsis.  The  term  septi- 
cemia was  meant  to  cover,  probably,  some  local  infections,  as  well  as 
mycotic  invasion  of  the  blood,  but  particularly  infection  of  the  blood 
by  the  organisms  of  suppuration.  That  the  common  pyogenic  bacteria 
are  not  the  exclusive  source  of  septicemia  is  shown  by  the  reported 
instances  of  clinically  typical  cases  of  the  <iisease.  without  the  presence 

'  See  page  90. 


378  GENERAL  PATHOLOGY. 

of  the  pyogenic  cocci,  but  resulting  from  the  action  of  other  bacteria, 
as  the  diplococcus  of  pneumonia,  Bacillus  typhosus,  colon  bacillus. 
Bacillus  pvocyaneus,  and  other  organisms.  The  microbes  not  only  pro- 
liferate in'the  blood,  but  also,  in  occasional  cases,  are  found  pullulating 
on  the  walls  {mural  implantation)  of  some  part  of  the  circulator}^  system, 
as  the  valves  of  the  heart  in  ulcerative  or  malignant  endocarditis.  This 
colonization  on  the  walls  of  the  blood-vessels,  heart,  sinuses,  etc.,  may 
lead  to  the  development  of  thrombi;  and  from  these,  emboli;  or,  pos- 
sibly, massing  of  elements  in  the  blood  may  lead  to  emboli — emboli 
formed  in  transit.  The  last  is  a  questionable  hypothesis.  The  emboli 
formed  in  blood,  and  containing  bacteria,  are,  of  course,  septic,  and  at 
their  point  of  lodgment  engender  the  changes  already  considered  when 
discussing  embolism.  The  embolic  production  of  an  abscess,  or  of  ab- 
scesses, is  the  essential  element  of  pyemia,  a  disease  recognized  by  sur- 
geons as  septicemia  plus  the  infected  emboli  to  which  are  attributed 
the  metastatic  abscesses.  (See  Thrombosis  and  Embolism,  pp.  270 
and  27S.) 

The  fever  that  accompanies  the  septic  processes  is  peculiar,  on  ac- 
count of  the  remarkable  exacerbations,  which  usually  occur  daily;  and, 
in  the  graver  forms,  on  account  of  the  addition  of  repeated  rigors  or 
chills.  Rigors  are  not  restricted  to  septic  processes,  but  occur  also 
after  hemorrhage,  occasionally  after  shock,  and  as  a  poorly  understood 
purely  nervous  manifestation ;  they  constitute  the  most  marked  phenom- 
enon of  the  malarial  paroxysm. 

During  the  cold  stage,  or  chill,  there  is  a  determination  of  the  blood 
to  the  large  glandular  viscera  and  venous  trunks;  the  skin  is  thus  de- 
prived of  its  normal  heat  by  the  deficiency  of  its  blood-supply,  and 
the  cooling  of  the  cutaneous  nerves  affords  the  explanation  for  the 
patient's  sense  of  intense  chilHness.  That  the  low  temperature  is  purely 
a  cutaneous  phenomenon  is  shown  by  the  thermometer.  If  the  tem- 
perature be  obtained  in  such  a  way  as  to  estimate  the  actual  blood-heat, 
— as  in  the  rectum,  mouth,  or  axilla, — preventing  heat  dissipation  at  the 
point  at  which  the  temperature  is  being  taken,  the  temperature 
is  found  to  be  above  the  normal.  The  deficiency  of  the  cutane- 
ous circulation  lessens  heat  dissipation,  and  probably  at  the  same  time 
heat  production  is  increased.  Certainly,  in  some  fevers  there  is  an 
increase  of  heat  production,  as  abundant  evidence  is  not  wanting  to 
show  that  heat  dissipation  may  be  greater  than  normal,  and  yet  that 
elevation  of  temperature  may  persist — a  condition  impossible  without 
persistent  overproduction.  The  rigors  associated  with  reduction  of  sur- 
face temperature  due  to  the  exposure  of  the  body  to  a  medium  the 
temperature  of  which  is  low,  appear  to  be  reflex  phenomena,  brought 
about  by  an  attempt  on  the  part  of  the  economy  to  produce  more  heat 
in  response  to  the  recognized  surface  fall.  They  are  to  a  certain  extent 
under  the  control  of  the  will.  The  amount  of  temperature  reduction 
necessarv  to  the  production  of  a  rigor  is  usually  not  over  from  0.5°  to 
1°  C.  It  is  interesting  to  observe  that  in  pyrexia  a  chill  results  when- 
ever the  surface  temperature  is  from  0.5°  to  1°  C.  lower  than  the  internal 
temperature.  After  persisting  a  varying  length  of  time,  the  chill  ends 
by  a  return  of  the  blood  to  the  skin,  and  usually  rapid  heat  dissipation, 
though  by  no  means  always,  followed  by  a  marked  decline  in  body- 
temperature. 


TKMPKKATl'KK   CHANCES.  ,^79 

The  acme  or  jastii:,iiini  of  the  fever  may  be  «iuickly  reached;  its 
duration  may  be  brief,  or,  in  other  cases,  the  fever  may  ]jersist  at  about 
the  same  point  for  a  considerable  lenj^h  of  time,  usually  showing  slight 
matinal  and  vesper  oscillation.  The  fever  may  disai)pear  within  a  few 
hours  {crisis)   or  may  gradually  subside,   recjuiring  many  days  {lysis). 

Whether  preceded  by  a  chill  or  not,  the  acme  of  the  temperature- 
rise  is  commonly  followed  by  a  progressive"  decline,  associated  with 
hyperactivity  of  the  emuncto'ries,  particularly  the  skin.  This  gradual 
decline  usually  begins  in  the  afternoon  or  early  evening  and  progresses 
through  the  night,  with  the  early  morning  temperature  the  lowest,  the 
rise  beginning  at  this  time  and  reaching  its  height  during  the  afternoon. 
During  the  twenty-four  hours  the  fever  may  disappear,  only  to  reappear 
in  a  few  hours;  this  type  is  said  to  be  intermittent.  In  the  remittent 
type  there  is  more  or  less  marked  remission,  but  no  period  of  complete 
apvrexia. 

The  active  causes  producing  this  rhythmic  alteration  in  temper- 
ature are  obscure.  It  is  maintained  that  the  accumulation  of  pyro- 
genous  material,  and  its  tendency  toward  fever  production  in  the 
svstem,  is  at  first  compensated  by  the  thermotactic  powers;  eventu- 
ally, the  failure  to  excrete  the  poison  as  rapidly  as  produced  permits 
of 'such  excessive  accumulation  that  the  heat-regulating  forces  are 
inadequate  to  the  task  of  maintaining  a  constant  temperature.  This 
is  followed  by  a  rise,  w^hich  continues  until  the  exhausted  centers — 
which  normally  responded  to  slight  temperature  variations  by  adjust- 
ment of  the  mechanism  between  heat  production  and  heat  dissipation — 
respond  to  the  more  urgent  demand  for  heat  dissipation  by  a  pseudo- 
crisis,  during  which  the  temperature  falls.  The  depressed  or  exhausted 
center,  not  responding  to  the  slight  changes  that  would  affect  it  in 
health,  now  permits  another  accumulation  of  heat,  which  again  sets 
it  off,  the  process  being  repeated  day  after  day  as  long  as  the  pyrogenous 
material  is  thrown  into  the  circulation. 

Paradoxic  Pyrexia. — None  of  the  hypotheses  at  present  available 
explains  satisfactorily  the  occurrence  of  what  Dr.  Savage  has  called 
"mad  calorific  areas."  Such  a  condition  is  illustrated  by  a  case  re- 
ported by  Knowling.  in  which  at  one  time  the  temperature  was  99.4°  F. 
in  the  left  axilla  and  105°  F.  in  the  right.  An  explanation  that  at  once 
suggests  itself  is  that  vascular  dilatation  on  one  side  of  the  body  or  in 
a  certain  area  permits  ready  access  of  the  blood  coming  from  the  viscera, 
resulting  in  higher  temperature,  while  a  less  active  peripheral  circulation 
in  other  parts  of  the  body  to  a  certain  extent  conceals  the  internal 
hyperthermia.  Often  there  is  no  evidence  of  such  vascular  dilatation, 
and  in  the  absence  of  phenomena  that  would  favor  this  conclusion  it 
would  probablv  be  wrong  to  accept  it  as  final. 

It  has  been' held  that  thermolysis  may  be  increased  upon  the  opposite 
side,  and  hence  the  tem])erature-rise  is  marked  upon  the  side  in  which 
thermolvtic  activity  is  diminished.  With  regard  to  this  theory  and  to 
the  opinion  previously  given,  it  can  only  be  said  that  both  are  specu- 
lative, and  that  neither  rests  upon  a  basis  of  fact  that  would  justify 
us  in  formulating  a  definite  opinion  at  this  time. 

With  the  rise  in  temperature  certain  circulatory  phenomena  manifest 
themselves.  Thus,  for  every  degree  Fahrenheit  (o. 55"^  C.)  that  the  body- 
temperature  rises,   the  pulse-rate  is  increased  about  ten  beats.     This 


380  GENERAL  PATHOLOGY. 

observation  is  approximately  correct  for  elevations  of  temperature 
within  two  or  three  degrees,  but  with  higher  temperatures  a  greater 
rise  occurs;  Liebermeister  showed  that,  for  the  1°  C.  above  41°  C, 
the  number  of  heart-beats  increased  27. 

During  the  earlier  stages  of  fever  the  blood-pressure  is  likely  to  rise 
also,  but  the  early  relaxation  of  the  vasomotor  nerves — probably  due 
to  exhaustion,  degenerative  changes,  or  inefficient  nutrition — is  fol- 
lowed by  a  fall  in  blood-pressure.  More  important  than  the  disturbance 
of  blood-pressure,  although  no  doubt  largely  due  to  the  same,  is  the 
change  iti  the  blood  distribution;  in  fever  the  latter  often  varies  greatly, 
as  already  stated  when  considering  the  dissipation  of  the  abnormal 
heat.  The  large  glandular  viscera  are  not  infrequently  perceptibly 
altered  b}^  the  increased  amount  of  blood  sent  to  them,  and  by  its 
relative,  if  not  absolute,  stagnation  in  their  interior. 

Blood  Changes. — The  blood  is  materially  lessened  in  nutritive  value, 
partly  as  a  result  of  the  interference  with  assimilation,  both  primary 
and  secondary,  and  partly  from  the  destruction  of  the  blood  elements. 
The  hemolysis  is  not  usually  manifest  until  the  fever  subsides,  not  hav- 
ing been  marked  previously  by  reason  of  the  concentration  of  the 
blood,  so  that  a  blood  examination  during  the  height  of  the  fever  fails 
to  disclose  the  loss  of  globular  elements  until,  by  dilution,  after  the 
fever  has  disappeared,  the  oligocythemia  and  oligochromemia  become 
apparent. 

Changes  in  Organs. — In  considering  alterations  that  occur  in  the 
tissues  we  are  at  once  confronted  with  the  difficult  task  of  differentiating 
lesions  that  are  due  to  the  febrile  process  alone  from  lesions  that  are 
dependent  upon  the  action  of  poisonous  agents — such  as  toxins,  etc. — 
that  were  themselves  etiologic  factors  in  the  production  of  the  fever. 
It  is  not  improbable  that  many  of  the  tissue  alterations  attributed  to 
the  rise  in  temperature  alone  are  truly  dependent  upon  the  action  of 
the  poisons  that  brought  about  the  fever.  In  addition  to  the  changes 
in  the  blood,  other  tissues  show  marked  alteration.  The  large  glandular 
viscera,  particularly  the  liver  and  kidneys,  exhibit  cloudA'  swelling;  a 
similar  change  occurs  in  the  muscles,  the  heart  often  manifesting  the 
granular  alteration  of  its  fibers  to  the  highest  degree.  Hyaline  change 
in  the  muscles  has  also  been  observed.  The  adipose  tissues  sooner  or 
later  show  wasting,  and  the  nerve  elements  evince  the  granular  and 
pigment  alterations  incident  to  exhaustion.  The  mucous  membranes, 
that  of  the  alimentary  canal  in  particular,  present  granular  and  fatty 
changes.  Many  of  the  tissue  changes  may  arise  from  contact  with  the 
poisons  circulating  in  the  blood;  others  are  possibly  due  to  the  accom- 
panying elevation  of  temperature  and  to  associated  disturbances  of 
nutrition. 

Beneficence  of  Pyrexia.^ — Experimental  evidence  has  seemed  to 
demonstrate  that  a  rise  in  the  body-temperature  mav  be,  in  certain 
infections,  distinctly  beneficial.  In  pneumococcous  infection  it  has  been 
found  that  resistance  is  increased  by  maintaining  the  animal  at  a  tem- 
perature between  41°  and  41.5°  C.  Similar  results  have  been  obtained 
with  the  streptococcus  of  erysipelas  and  with  a  few  other  organisms. 

^  L6\vy  and  Richter,  "Berlin,  klin.  Woch.,"  1S97,  No.  9;  also  "Centralbl.  f. 
inn.  Med.,"  July  17,  1S07.  Lowit,  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.,"  Dec. 
15,  1898.      Beniasch,  "Zeit.  f.  klin.  Med.,"  Bd.  xlv,  Hefte  i  u.  2. 


TKMJM-UATL'kK   ClIANllKS.  381 

Sln)ukl  lurllKT  research  estaMish  ihe  correctness  of  these  experiments, 
it  is  not  impossible  tliat  we  may  have  to  revise,  indeed  reverse,  (nir 
views  as  to  the  essential  etiologic  factors  active  in  fever  production. 
Thus,  it  may  be  shown  that  leukolysis  and  liberation  within  the 
body-fluids  of  antimicrobic  substances  belong  to  the  protective  phenom- 
ena, and  that  these  bodies  can  bring  al)Out  the  elevation  of  temperature, 
which  is  itself  a  part  of  the  reaction  by  which  immunity  is  evolved. 
Investigations  directed  along  this  line  may  show  that  the  temperature- 
rise  accompanying  the  malarial  paroxysm  is  the  cause  of  sporulation, 
and  that  the  latter  is  not  the  cause  of  fever,  as  at  present  is  held. 
In  the  existing  state  of  our  knowledge  such  suggestions  can  scarcely  be 
dignified  by  calling  them  even  hypotheses;  the  fact  that  fever  accom- 
panies infection — indeed,  seems  to  be  its  most  constant  com|)anion — • 
demands  a  l^etter  explanation  than  is  at  present  available. 


PART  III. 
SPECIAL  PATHOLOGY 


PART  III.— SPECIAL  PATHOLOGY. 

CHAl'TKR    I. 

THE     BLOOD.  ' 

TECHNIC  OF  BLOOD  EXAMINATION. 

Examination  of  the  Blood. — Blood  is  examined  microscopically  to 
determine  the  number  and  character  of  the  corpuscles  and  their  relative 
proportion,  and  the  presence  or  absence  of  parasites,  either  vegetable  or 
animal.  Examination  in  the  fresh,  unstained  condition  should  be  fol- 
lowed by  a  study  of  stained  specimens.  Estimation  of  the  hemoglobin 
is  also  of  the  greatest  importance. 

Obtaining  the  Blood. — The  lower  part  of  the  lobe  of  the  ear  or  the 
tip  of  the  ring-finger,  l^ecause  of  their  accessibility,  are  the  points  usually 
selected  for  drawing  the  blood;  other  areas  may  l)e  equally  available. 
The  region  chosen  should  be  free  from  edema,  inflammation,  or  any 
other  morbid  process  likely  to  give  rise  to  the  presence  of  other  fluids 
that  may  become  mixed  with  the  flowing  blood.  Cleanse  carefully  the 
selected  site,  first  with  water,  then  with  alcohol,  rubbing  briskly  with 
a  towel  thoroughly  to  dry  the  part ;  this  will  induce  hyperemia  sufficient 
to  cause  free  flow  of  the  blood.  With  a  lance-shaped  needle  prick 
the  skin  quickly  and  to  a  good  depth.  The  author  is  averse  to  the 
continuous  use  of  a  single  instrument,  and  therefore  hesitates  to  recom- 
mend any  of  the  many  devices  for  pricking  the  skin.  There  is  no 
reason  for  the  repeated  use  of  the  same  instrument.  A  pen,  preferably 
of  steel,  with  one  nib  broken  off,  as  recommended  by  a  number  of 
observers,  is  cleanly  and  inexpensive,  enabling  one  to  use  a  different 
instrument  for  each  observation.  Let  the  first  few  drops  escape  and 
wipe  them  off,  using  for  examination  only  the  blood  that  follows.  Have 
at  hand  at  least  a  dozen  cover-glasses,  carefully  cleaned  in  acid  alcohol 
followed  by  alcohol  and  careful  wiping;  also  four  slides  cleaned  in 
the  same  way.  A  square  cover-glass,  gently  warmed,  not  hot,  is  al- 
lowed to  touch  a  small  drop  of  l)lood;  a  droplet  adheres,  and  the  cover- 
glass  is  inverted,  drop  downward,  on  a  warm,  clean  slide.  As  soon  as 
the  blood  runs  to  the  edge  of  the  cover-glass,  with  a  sable  brush  cedar 
oil — conveniently  obtained  from  the  immersion  oil  that  accompanies 
the  microscope — or  vaselin  is  painted  around  the  edge  to  exclude  air 
and  to  prevent  drying.  The  slide  is  now  ready  for  examination.  A 
second  and  a  third  slide  are  prepared  in  the  same  manner.  A  very 
satisfactory  method  for  ol)taining  slides,  with  minimal  exposure  of  the 
blood  to  the  air,  is  to  take  a  thoroughly  clean  slide  and  cover-glass, 

'  The  literature  and  full  clinical  studies  of  diseases  of  the  blood  will  be  found 
in  Da  Costa's  "Clinical  Hematoloj:^',"  Phila.,  i"^- 
26  '        385 


386  SPECIAL  PATHOLOGY. 

SO  adjusting  them  that  the  cover  on  top  of  the  sHde  comes  even  with 
the  edge;  when  the  edge  is  presented  to  the  drop  of  blood,  barely  touch- 
ing it,  the  blood,  by  capillary  action,  flows  between  the  two  glasses. 
Slides  so  prepared  can  not  be  so  readily  sealed,  but  when  the  space 
between  the  cover-glass  and  the  slide  is  completely  filled,  drying  of 
the  serum  at  the  margin  more  or  less  perfectly  excludes  the  air.  Such 
temporarv  mounts  will  not  keep,  and  must  be  examined  at  once,  using 
first  low  powers  and  then  higher.  To  make  films,  one  cover-glass  is 
touched  to  a  drop,  so  that  the  center  of  the  glass  receives  the  droplet; 
immediately,  a  second  cover-glass  is  dropped  on  the  first,  care  being 
taken  that  the  corners  do  not  coincide;  if  the  glasses  are  clean,  the 
blood  quickly  flows  to  the  edge;  at  once  separate  the  two  covers  by 
sliding  them  apart,  carefully  avoiding  any  lifting  motion;  dry  quickly, 
but  avoid  heating  while  moist.  From  each  case,  at  least  eight  or  ten 
spreads  should  be  prepared  in  this  way.  Some  prefer  glass  slide  films 
made  by  drawing  one  slide,  to  the  end  of  which  adheres  the  blood, 
over  a  second  slide  at  an  angle  of  45  degrees,  the  blood  being  in  the 
acute  angle.  If  certain  staining  methods  are  to  be  employed,  the  films 
must  now  be  fixed. 

Fixation  of  Films. — The  method  usually  advised  for  fixing  is  by  heat, 
as  in  a  hot-air  oven  or  sterihzer  at  125°  to  140°  C.  for  twenty  to  thirty 
minutes,  the  lower  temperature  requiring  the  longer  time.  Ordinarily, 
satisfactory  results  will  be  obtained  if  the  temperature  be  slowly  raised 
to  between  125°  and  130°  C,  the  heat  withdrawn,  and  the  oven  per- 
mitted to  cool  slowly.  Ovens  constructed  on  the  principle  of  hot-air 
sterilizers,  (see  Bacteriologic  Technic)  are  best  adapted  for  the  fixation 
of  films.  In  the  absence  of  an  oven  a  copper  plate  or  strip  is  con- 
venient; a  strip  from  5  to  10  cm.  wide  and  from  20  to  30  cm.  long, 
supported  over  a  flame  and  protected  from  drafts  of  air,  answers  very 
well.  The  flat-iron-shaped  table  (Fig.  30,  p.  35)  may  be  used  in  the 
same  wav.  Placed  at  one  end,  the  flame  soon  heats  the  strip  so  that 
at  any  point  a  fairly  constant  temperature  is  maintained.  By  dropping 
water  on  this  plate  at  various  points  a  place  is  found  where  water 
boils;  drop  the  cover-glass  on  this  point,  turning  the  film  side  down; 
about  twenty  minutes  will  be  needed  for  fixing.  A  number  of  com- 
petent observers  fix  the  dried  films  in  the  same  manner  as  spreads  of 
bacteria.  (See  Bacteriologic  Technic.)  For  a  finer  study  of  the  nuclei 
in  blood-cells,  and  when  recognition  of  the  granules  is  not  so  important, 
some  of  the  fixatives  recommended  in  Chapter  II,  Part  I,  may  be  used; 
solutions  containing  bichlorid  of  mercury,  and  also  the  osmic  acid  solu- 
tions, may  find  special  application.  (See  p.  34.)  Coyer-glass  films  may 
be  fixed  by  immersion  in  a  mixture  of  equal  parts  of  absolute  alcohol 
and  ether  for  half  an  hour,  followed  by  drying.  After  fixation  by  any 
of  the  foregoing  methods  the  covers  may  be  stained  at  leisure. 

Staining. — Properly  prepared  and  fixed  films  are  grasped  in  the 
cover-glass  forceps  used  for  staining  bacteria.  The  stain  may  be 
applied  to  the  cover,  or  the  cover,  grasped  in  Kalteyer's  forceps,  may 
be  immersed  in  a  dish  containing  the  stain.  Slides  had  best  be  placed 
in  jars  of  the  stain. 

Stains. — Wright's  Stain. — This  is  one  of  the  latest  and  in  some 
respects  the  best  of  the  numerous  methylene-blue-eosin  stains  now  in 
common  use,  other  well-known  members  of  the  group  being  those  de- 


Till-: 


r<i. 1)1)0.  387 


vised  by  Xocht.  GoKlhorn,  Jcnncr,  and  Lcisliinan.'  The  chief  points 
of  superiority  are  that  special  tixation  of  lihiis  is  not  ref|uired,  and 
blood-plates,  basoi)hilii'  j,'ranules,  and  malarial  ]»arasites  are  well  stained. 
The  preparation  of  Wright's  stain  is  a  complex  ])rocedure  and  need 
not  here  be  given.  The  technic  for  employing  it  is  brietiy:  (i)  Cover 
thin,  air-dried  films  with  the  stain  for  one  minute.  (2)  Add  to  the 
stain  water,  drop  by  drop,  until  an  iridescent  scum  forms  on  the  surface; 
for  ^-inch  square  cover-glass  films,  4  to  8  drops  usually  suffice.  Allow 
the  diluted  stain  to  act  for  two  or  three  minutes.  (3)  Wash  witli  water, 
preferably  distilled,  until  the  film  becomes  pink  or  yellow  in  color. 
(4)  Blot  with  filter-paper,  air  dry.  without  heat,  and  mount  in  balsam. 
Results:  Erythrocytes,  orange  or  pink;  nuclei  of  leukocytes  and  crvthro- 
blasts,  dark  blue  to  lilac;  cytoplasm  of  lymphocyte,  robin's  egg  blue, 
of  hyaline  cell,  pale  to  dark  blue;  neutrophile  granules,  reddish-lilac; 
eosinophile  granules,  pink;  basophile  granules,  blue  to  royal  purple; 
blood-plates,  pale  blue  with  dark  lilac  or  blue  granules.  Films  more 
than  a  few  weeks  old  are  apt  to  yield  unsatisfactory  results;  this  may 
be  partially  overcome  by  fixing  with  the  undiluted  stain  for  at  least 
two  minutes  and  staining  four  or  five  minutes  after  dilution. 

Ehrlich's  Triacid  Stain. — A  mixed  powder  for  the  preparation  of 
Ehrluli's  stain  is  on  the  market,  but  solutions  prepared  from  it  are 
rarely  satisfactory;  for  this  reason  it  is  recommended  that  the  stain  be 
made  from  concentrated  aqueous  solutions  of  the  dyes.  The  solutions 
are  all  to  be  saturated,  and  the  quantities  given  will  insure  saturation 
from  almost  all  samples,  but  as  the  dyes  vary  in  solubility,  different 
samples  may  require  slightly  more  or  less  of  the  dye.  As  it  is  best  not 
to  filter,  and  as  only  the  supernatant  fiuid  is  to  be  used,  it  will  be 
found  convenient  to  make  up  all  these  stains  in  tall,  narrow  bottles, 
and.  while  more  expensive,  Grubler's  stains  had  best  be  used. 

r.   Saturated  aqueous  solution  of  orange  G: 

Orange  G 6  gm. 

Distilled  water,  100  cc. 

2.  Saturated  aqueous  solution  of  acid  fuchsin; 

Acid  fuchsin  (fuchsin  S) q  gm.  ^ 

Distilled  water 100  cc. 

3.  Saturated  aqueous  solution  of  methyl-green: 

Methyl-green  (OO  cryst.) 6  gm. 

Distilled  water.  100  cc. 

These  stock  solutions  keep  well.  The  niixoil  stain  prepared  from 
them  has  not  such  good  keeping  qualities,  and,  while  not  ripe  for  the 
best  results  under  one  week,  after  two  or  three  weeks  usually  does 
not  stain  so  well;  occasionally,  howev^er.  a  sample  may  give  fairly 
good  results  for  months.  A  little  experience  enables  one  to  see  which 
of  the  three  dyes  is  deficient,  and  by  adding  a  trace  of  the  required 
stain,  the  mixture  can  be  improved.  Hardly  any  two  blood  cases  stain 
alike,  and.  for  the  best  results,  slight  changes  in  the  formula  may  be 
made  in  order  to  overcome  this  defect.      Ehrlich's  formula,  as  given 

'  For  an  admirable  summary  of  these  stains  see  article  by  Baumgarten, 
"American  Medicine,"  T.nm.irv  ^    i>)04. 


388  SPECIAL  PATHOLOGY. 

by  Cabot,   and  the  Johns  Hopkins  formula,   as  given   by   Simon,   are 
as  follows,  made  from  the  foregoing  stock  solutions: 

Ehrlich's  Formula. 

Saturated  watery  solution  of  orange  G, 6  c.c. 

"  "    '  "         •'    acid  fuchsin, 4    " 

To  these  add  a  few  drops  at  a  time,  shaking  between  each  addition, 
Saturated  watery  solution  of  methyl  green, 6.6  c.c. 

Then  add:  •  . 

Glycerin 5  c.c. 

Absolute  alcohol 10     " 

Water, 16    " 

Shake  well  for  one  or  two  minutes.      Let  stand  twenty-four  hours. 

Johns  Hopkins  Formula. 

Orange  G  solution " 13  to  14  c. 

Acid  fuchsin  solution, 6  "      7 

Distilled  water 15 

Absolute  alcohol, 15 

Methyl-green  solution, 12.5' 

Absolute  alcohol, 10 

Glycerin, 10 

After  the  methyl-green  is  added,  stir  while  remainder  of  alcohol  and  glycerin 
is  slowly  mixed  with  the  other  constituents. 

In  the  preparation  of  the  stain  it  is  important  that  the  definite 
order  given  be  followed  in  the  mixing  of  the  foregoing  ingredients. 
Stain  the  fixed  films  for  from  two  to  five  minutes,  wash  in  distilled 
water,  dry,  and  mount  in  balsam.  Results:  Erythrocytes,  orange; 
nuclei  of  leukocytes  and  erythroblasts,  blue  or  greenish-blue;  neutro- 
phil granules,  lavender;  eosinophile  granules,  copper  red;  basophile 
granules,  unstained. 

Kanthack  and  Hardy  especially  recommend  a  0.5  per  cent,  solution 
of  eosin  in  seventy  per  cent,  alcohol;  stain  for  thirty  seconds,  rinse 
in  water,  dry  by  gentle  pressure  between  folds  of  filter-paper,  pass 
three  times  through  the  flame,  and  counterstain  in  Lofjicrs  mcthylene- 
blue  solution.  (See  p.  48.)  For  the  demonstration  of  structurally 
imperfect  red  cells  a  one  per  cent,  solution  of  eosin  (water  soluble) 
in  fifty  per  cent,  alcohol,  followed  by  washing  in  water  and  then  by 
hematoxylin,  gives  satisfactory  results. 

A  special  stain  for  the  "mast  cell"  is  prepared  as  follows: 

Saturated  alcoholic  sokition  of  dahHa,  filtered, 50        parts. 

Glacial  acetic  acid 10-15 

Distilled  water, 100 

Stain  for  twenty-four  hours,  wash  in  water,  dry,  and  mount  in 
balsam.  Satisfactory  stains  of  this  cell  may  be  obtained  by  the  use 
of  carbol-toluidin-blue  (p.  48)  applied  for  a  few  minutes,  followed  by 
differentiation  in  glycerin  ether  (p.  49);  the  granules  are  more  sharply 
outlined  by  this  method,  and  the  results  are  more  uniform. 

lodin  Reaction. — The  term  iodin  reaction,  or  iodophilia,  is  used  to 
designate   the   reaction   occurring   under   certain   conditions   when   the 


THE  ni.ooi).  ^89 

blood  is  subjecttnl   to   tlu'  action  of  iodiii.     The  solution   ustiallv  cm- 
ployed  consists  of: 

lodin I  part. 

Potassium  iodiil ^  parts. 

Gum  arabic 50       " 

Distilled  water 100 

An  air-dried  film  of  blood  is  covered  with  this  syrupy  solution, 
wliich  is  allowed  to  act  for  two  or  three  minutes;  the  excess  is  then 
drained  off  and  the  cover-glass  placed  blood-side  dow'nward  on  a  slide. 
A  more  rapid,  but  less  neat,  method  is  to  place  a  large  drop  of  the 
solution  near  one  end  of  a  slide  and  invert  upon  it  the  cover-glass, 
which  in  two  or  three  minutes  is  moved  to  the  center  of  the  slide,  leaving 
behind  the  thick  layer  of  fiuiil.  These  preparations,  being  mounted  in 
the  staining  medium,  are  not  pennanent.  Examined  under  the  oil- 
immersion  lens,  the  red  cells,  normal  leukocytes,  and  blood-plasma  are 
found  to  be  stained  a  uniform  pale  yellow.  A  positive  iodin  reaction 
consists  of  the  presence  of  variable  sized  granules,  ranging  in  color 
from  brownish-yellow  to  deep  brown,  which,  in  location,  are  intracellular 
or  extracellular.  The  former  are  almost  exclusively  within  the  poly- 
morphonuclear leukocytes.  Instead  of  distinct  granules,  there  is  in 
some  instances  a  diffuse  brownish  discoloration  of  the  cytoplasm.  The 
extracellular  granules,  less  often  found  and  relatively  of  little  impor- 
tance, are  free  in  the  plasma.  The  significance  of  the  reaction  is  vari- 
ously estimated.  It  is  observed  in  cases  of  sepsis,  and  most  frequently 
when  suppuration  has  occurred,  but  is  not  a  positive  indication 
of  the  presence  of  pus.  It  is  also  found  quite  constantly  during  the 
course  of  pneumonia,  pulmonary  tuberculosis,  malignant  disease,  certain 
of  the  grave  anemias,  and  occasionally  in  other  affections.  Apparently 
depending  upon  degenerative  changes  in  the  leukocytes,  the  real  diag- 
nostic value  of  this  reaction  is  not  as  yet  determined. 

Staining  Diabetic  Blood. — Bremer's  observations  on  the  peculiar 
stain  reactions  of  diabetic  blood  appear  to  deserve  much  more  con- 
sideration than  they  have  received.  From  a  number  of  experiments 
•in  the  author's  laboratory'  I  am  convinced  that  certain  information 
may  be  obtained  by  Bremer's  methods,  and  that  the  test  is  deser\'ing 
of  consideration.  It  requires  constant  control  under  nearly  all  condi- 
tions, and  hence  every  examination  should  be  verified  by  applying  the 
test  to  blood  known  to  be  normal  as  well  as  to  the  suspected  sj^ecimen. 
Thick  films  of  the  blood  under  examination  and  control  films,  both 
prepared  in  the  usual  way,  are  fixed  by  heat  at  a  temperature  of  it,$°  C. 
The  two  covers  are  then  grasped  l)ack  to  back,  so  that  both  films  are 
exposed,  and  are  immersed  in  either  a  one  per  cent,  watery  solution 
of  Congo  red  or  a  one  per  cent,  watery  solution  of  Biebrich  scarlet 
for  about  two  minutes.  The  films  are  then  washed  in  water  and  dried. 
Congo  red  stains  the  normal  blood  and  not  the  diabetic:  Biebrich 
scarlet  stains  the  diabetic  blood  and  not  the  normal.  Other  anilin 
dyes  may  be  applied  in  a  similar  manner.  The  important  point  to  be 
recognized  is  that  diabetic  blood  is  never  stained  to  the  same  degree, 
and  often  not  the  same  shade,  as  the  normal  blood.  The  reaction  is 
sometimes  obtained  in  conditions  other  than  diabete>. 


39° 


SPECIAL   PATHOLOGY. 


ESTIMATION  OF  THE  HEMOGLOBIN. 

Gowers'  Hemoglobinometer. — This  apparatus  consists  of  two  glass 
tubes  of  exactly  the  same  size;  one  contains  a  standard  solution,  the 
tint  of  a  dilution  of  20  c.mm.  of  blood  in  2  c.c.  of  water  (i  :  100).^  The 
second  is  graduated  into  100  degrees,  and  is  arranged  to  contain  2  c.c. 
(a  hundred  times  20  c.mm.).  or  more,  when  the  percentage  of  hemo- 
globin is  above  100. 

Twenty  cubic  millimeters  of  blood  are  measured  by  the  capillary 
pipet  and  ejected  into  the  bottom  of  the  graduated  tube,  a  few  drops 
of  distilled  water  being  placed  first  in  the  latter.  The  mixture  is  rapidly 
agitated  bv  a  rinsing  movement,  and  distilled  water  is  then  added, 
drop  bv  drop,  until  the  tint  of  the  dilution  is  the  same  as  that  of  the 
standardized  tube.     The   degree  of   dilution  indicates  the   amount   of 

hemoglobin,  and  may  be 
read  off  from  the  graduated 
tube. 

Von  Fleischl's  Hemo- 
globinometer,— The  stan- 
dard of  comparison  in  this 
instrument  is  an  elongated 
wedge  of  glass,  tinted  with 
Cassius'  golden  purple,  and 
mounted  movably  beneath 
a  platform  or  stage  like 
that  of  a  dissecting  micro- 
scope. In  the  center  of  the 
platform  is  a  circular  open- 
ing, through  which  the 
light  from  a  candle  or  lamp 
is  reflected  upward  from  a 
disc  of  plaster-of-Paris. 

The  wedge  of  glass  un- 
derlies one-half  of  the  cir- 
cular opening  in  the  plat-- 
form.  Above  the  wedge, 
and  exacth'  over  the  cir- 
cular opening,  rests  a 
metallic  tube,  1.5  cm.  long, 
with  a  vertical  metallic  partition  and  a  glass  bottom.  One-half 
of  the  tube  overlies  the  wedge  and  receives  its  light  through  it. 
•This  half  is  filled  with  distilled  water,  and  in  the  other  half  is 
placed  the  mixture  of  blood  and  water.  The  blood  is  received  from 
the  finger  into  a  minute  glass  tube  by  capillary  attraction  (auto- 
matic pipet)  and  is  placed  in  the  proper  compartment,  thoroughly 
mixed  with  water, — care  being  taken  to  see  that  the  measuring  tube 
is  -^washed  free  from  blood, — and  both  compartments  are  filled  with 
water.  In  order  to  make  accurate  readings  the  observations  must  be 
made  in  a  dark  room  or  closet,  using  no  other  illumination  than  that 
afforded  by  a  lamp  or  candle.     The  red  glass  wedge  is  then  moved  in 

1  In  reality  this  represents  a  dilution  of  i  :  loi.  but,  as  allowance  is  made  in 
the  graduated' tube  for  this  error,  it  is  a  matter  of  no  practical  importance. 


Fig.  213. — Gowers'  Hemoglobinometer.  Lmproved  Form. 
A  and  B  are  flattened  tubes,  A  being  permanently  sealed  and 
containing  the  tint  standard;  B  is  graduated  and  is  used  for 
diluting  the  blood.  C  is  a  pipet  for  measuring  the  blood,  as 
directed  in  the  test.  Just  in  front  of  the  case  is  shown  the 
needle  usually  recommended  for  puncturing  the  skin.  The 
dropping-bottle  shown  in  the  illustration  contains  distilled 
water  for  diluting  the  blood. 


TIIH    lU.(KiI). 


391 


one  (lircctii)n  or  the  rt-verse  until  the  two  lluiils  show  an  equal  intensity 
of  red  color.  The  number  indicated  on  the  scale,  read  ofT  at  M  (see 
Fig.  214),  IS  the  percentage  of  hemoglobin.  As  soon  as  the  automatic 
capillary  pipet  is  emptied  into  the  chamber  n  and  rinsed  free  of  the 
adhering  blood,  it  should  be  placed  in  water  or  in  a  one  ])er  cent,  solution 
of  carbonate  of  sodium,  and  should  never  be  j^ermitted  to  dry 
until  it  has  been  thoroughly  cleanse<l.  Immediately  after  comi)leting 
the  observation  the  mixing  cell  G  is  thoroughly  washed  and  dried;  the 
capillary  \npet  is  also  cleansed  by  rei)eated  washing  in  the  alkaline 
solution,  followed  by  water,  or  in  w^ater  alone.  It  is  then  <lried  by 
passing  a  thread  of  cotton,  silk,  or  floss  through  the  cajjillary  tube;  a 
threaded  needle  is  sometimes  advised  for  this  puqxjse,  but  chipping 
of  the  wall  of  the  tube  may  result  from  slight  carelessness  in  introducing 
the  needle,  and  a  hair 
doubled  on  itself  answers 
the  same  purpose  without 
the  danger  indicated.  The 
two  ends  of  the  hair  are 
passed  through  the  tube, 
and  the  resulting  loop  is 
used  as  a  carrier  for  the 
thread,  which  completes 
the  cleaning  and  drying. 
The  l)eginner  should  see 
that  the  instrument  is 
clean  before  the  various 
I)arts  are  put  away;  the 
experienced  worker  is  fully 
aware  of  the  difficulty  en- 
countered in  cleaning  a 
dried  pipet,  and  therefore 
does  not  need  the  precau- 
tionary advice  given  to  the 
novice. 

The  mixing  pipet  of 
each  instrument  is  adapted 
to  that  i)istrnmcut  only,  and 
bears  its  cajjacity  stamped 
upon  the  handle.  A  similar 
marking    is   made    on    the 

screw-head  at  the  back  of  the  stage,  and  as  all  parts  of  the  instrument 
are,  or  should  be.  numbered,  mixing  of  different  pieces  should  not  occur. 
In  order  to  avoid  confusion  or  incorrect  reading  where  a  number  of 
instruments  are  in  use.  and  when  ordering  new  pipets,  this  fact  must  be 
rememl)ered. 

Mieschers  modification  of  this  instrument  is.  in  the  hands  of  an 
expert,  more  accurate  than  the  original,  but  is  more  complicated  and 
costlv.  The  chief  ])oints  of  difference  are  the  use  of  two  mixing  cells 
differing  in  capacity,  each  with  a  projecting  partition  which  receives  a 
grooved  cover-glass,  and  a  sjiecial  mixing  pipet  for  the  blood. 

Oliver's  hemoglobinometer  consists  of:  (i)  The  automatic  blood 
pipet  (Fig.  215.  I  I.  which  has  a  capacity  '*"  •■'■'"  .-i.;,.  ,-.,in,,„,.t..rc  -.nrl 


!•  1,..     ..1.4.         \  i>N     i    1  1  F^i    Ml     -      1  1  I    M'  "    i  '  '111  N'  '%:►    I  I  K. 

MixitiK  crll,  flividwl  l>y  a  |«rtition  into  two  ch.imlKTS,  j  .infi  j'. 
The  lilfxxl  anil  water  arc  |)laci-<l  in  ii:   a'  rrcrivi-s  water  ,il..n<- 
and  is  riirectly  over  the  oJored   kI^iss  weilKO-     A.',    K     1  .1 
weflijc.     .U.   Point  at  which  rcadinK  is  taken.     T.   .Milli  ! 
whiih  moves  the  he.id    R,  whiih.  in   turn,  moves  the  <ai-: 
P,  P,  carryinK  the  tinted  glas-s  wcdnc.     S.  Disc  of  plaMrr  ol- 
I'aris  for  reflecting  the  light  upward  ihrnugh  the  glaM  wolgc 
and  the  mixinK  chamtier. 


392 


SPECIAL  PATHOLOGY. 


fills  readily  by  capillary  attraction.  It  differs  from  the  fragile  capil- 
lary measurer  that  accompanies  von  Fleischl's  instrument  in  being 
made  of  stout  glass,  and  is,  therefore,  more  serviceable.     The  bore  is 


Fig.  215. — Oliver's  Hemoglobinometer. 
a.  Standard  gradations      b.  Lancet,     c.  Capillary  measuring-pipet.     d.  Mixing  pipet.     e.  Blood-cell  and  cover- 
glass. 

dried  before  an  observation  by  passing  through  it  a  needle,  threaded 
with  darning  cotton.  The  handle  is  useful  for  stirring  together  the 
blood  and  water  in  the  blood-cell.     (2)  The  mixing  pipet  is  provided 


TIIK    HI.ooD.  3Q3 

with  a  rubber  nozle  that  lits  over  the  pohslieil  end  of  the  blood-measurer 
and  insures  complete  rinsinj^  out  of  the  blood  with  the  first  few 
drops  of  water.  (,0  The  blood-cell  is  of  a  capacity  more  than  sulli- 
cient  to  insure  the  c()mi)lete  liberation  of  the  hemoglobin.  It  yields 
a  blood  solution  of  rather  less  than  one  per  cent,  when  filled  level  with 
the  rim.  It  is  itself  the  measure  of  the  amount  of  water  to  l)e  added, 
and  may  be  easily  and  accurately  filled.  (4)  The  standard  grada- 
tions are  arranged  as  circular  discs  in  two  slabs— six  in  each ;  they 
represent  the  divisions  of  ten  degrees  of  the  scale  from  10  to  120  in- 
clusive. (5)  The  riders  are  small  squares  of  tinted  glass  provided  for 
reading  the  degrees  intervening  between  each  of  the  standard  grada- 
tions. When  they  are  used,  the  slip  of  colorless  glass  is  placed  over 
the  cover  of  the  blood-cell,  so  as  to  balance  the  effect  of  the  laver  of 
glass  in  the  rider,  which  is  laid  over  the  standarrl.  Two  sets  of  riders 
have  been  arranged:  one  suitable  for  physiologic  observation,  to  insure 
the  finer  readings, — c.  ^.,  of  one  degree, — and  the  other,  sufficient  for 
ordinary  clinical  observation,  to  enable  the  observer  to  determine  dif- 
ferences of  2.5  degrees.  For  the  reading  of  units,  nine  riders  are  re- 
quired, which  are  grouped  into  three  slides.  It  should  be  premised 
that  the  value  of  the  riders  is  the  same  neither  in  the  two  standards 
required  for  candle-light  and  daylight  nor  in  the  upper  and  lower  halves 
of  either  standard.  This  want  of  uniformity  arises  from  the  differences 
of  the  specific  color-curves  in  the  two  standards,  and  in  the  two  por- 
tions of  each.  In  the  six  lower  grades  of  both  standards  the  value  of 
each  rider  is  double  that  in  the  upper  six  gradations.  In  the  transi- 
tion grades — the  lowermost  of  the  upper  half  and  the  uppermost  of 
the  lower  half — this  rule  does  not  accurately  apply,  but  inasmuch  as 
the  departure  is  constant  in  all  observations,  and  is,  moreover,  slight,  it 
may  be  disregarded  for  the  sake  of  simplicity  in  using  the  riders. 

The  daylight  standard  is  less  adapted  to  the  finer  readings  than 
that  used  by  candle-light.  For  the  ordinary  reading  one  rider  is  used : 
namely,  that  which  is  equivalent  to  five  degrees  in  each  slab  of  the  stan- 
dards. Therefore  each  set  of  six  standard  gradations,  whether  for 
candle-light  or  daylight,  has  its  own  rider.  When  the  blood  solution  is 
deeper  in  color  than  any  particular  standard  gradation,  but  is  over- 
stepped by  the  rider,  the  mean  l^etween  the  two  may  be  taken  as  the 
reading;  and  the  same  rule  will  apply  when  the  color  of  the  blood  is 
higher  than  the  rider,  but  is  not  so  high  as  that  of  the  next  standard 
grade  above.  Hence,  this  single  rider  may  be  made  to  provide  read- 
ings of  0.25  and  0.75.  (6)  The  camera  tulic:  A  tube  of  simple  con- 
struction is  provided,  which,  being  collapsil)le,  will  pack  into  a  small 
compass  with  the  other  parts  of  the  apparatus.  (7)  The  light:  For 
observation  by  artificial  light  it  has  l»een  found  that  the  small-sized 
wax  candles  known  as  Christmas  candles  are  the  most  satisfactory  in 
affording  a  suitable  intensity  of  light,  and  a  light,  moreover,  that  is 
sutliciently  uniform.  The  position  of  the  candle  is  important.  It 
should  be  such  as  to  shed  an  equal  light  on  the  blood-cell  and  the  stan- 
dard, and  also  such  as  to  furnish  a  high  light,  so  that  the  flame  should 
be  three  or  four  inches  above  the  cells.  The  distance  must  be  reg- 
ulated bv  the  observer,  who  soon  learns  how  to  adjust  it  to  the  best 
advantage,  so  that  he  may  watch  the  colors  with  the  greatest  certainty 
and  accuracy.     The  actual  distance  does  not  affect  the  reading;    but 


394 


SPECIAL    PATHOLOGY. 


when  the  candle  is  placed  too  near  the  points  of  observation,  the  il- 
lumination becomes  too  strong,  and  is  somewhat  distracting,  especially 
when  the  lower  grades  are  under  observation,  these  requiring  less  light. 
To  Use  the  Instrument. — The  bore  of  the  blood-measurer  is  first  of 
all  dried  out  by  passing  through  it  a  needle  threaded  with  darning 
cotton,  and  then  the  polished  point  is  presented  to  the  drop  of  flow- 
ing blood,  obtained  as  directed  for  other  instruments  (p.  385).  Care 
must  be  taken  that  the  pipet  is  really  quite  filled;    and  if  it  has  been 

necessary  to  re-apply  it  to  the 
drop,  it  should  be  observed 
whether  there  is  a  break  in 
the  column  of  blood.  Any 
blood  adhering  to  either  end 
must  be  carefully  wiped 
away  with  the  finger.  The 
rubber  nozle  of  the  mixing 
pipet,  charged  with  water,  is 
adjusted  over  the  polished 
end  of  the  measuring  pipet, 
and  the  blood  is  washed  into 
the  blood-cell  by  pressing  the 
water  through,  drop  by  drop. 
The  handle  of  the  pipet  is 
then  used  as  a  stirrer,  and 
the  further  additions  of  water 
are  made  to  impinge  on  it, 
as  it  serves  to  graduate  the 
size  of  the  drops  required 
accurately  to  fill  the  cell.  It 
is  easy  to  do  this  when  the 
observer  catches  the  reflec- 
tion of  a  window  on  the  sur- 
face of  the  fluid.  A  final 
thorough  mixing  with  the 
handle  will  be  required,  and 
perhaps  another  slight  addi- 
tion of  water  may  be  neces- 
sary to  secure  a  level  filling. 
The  cover-glass  is  then  ad- 
justed, when  a  small  bubble 
should  form — a  sure  sign  that 
the  cell  has  not  been  over- 
filled. If  candle-light  is  to 
be  used,  the  instrument  must 
be  removed  to  a  darkened 
room,  as  alreadv  directed  for  von  Fleischl's  instrument  (p.  390).  The 
blood-cell  is  then  placed  by  the  side  of  the  standard  gradations,  and  the 
eve  quicklv  recognizes  its  approximate  position  on  the  scale.  Then  the 
camera  tube  will  more  accuratelv  define  it.  If  it  is  found  that  the  blood 
solution  is  matched  in  depth  of  color  by  one  of  the  standard  grades, 
the  observation  is  at  an  end;  but  if  it  is  observed  to  be  higher  than 
one  gradation,  but  lower  than  that  above  it,  the  blood-cell  is  placed 


Fig.  216. — Dare's  Hemoglobinometer. 
(Parts  assembled  as  when  in  use.  About  one-half  actual  size.) 
I. — R.  Milled  head,  which  rotates  a  rulAer-covered  cylinder 
that,  in  turn,  acts  upon  the  color-comparison  prism  V.  S. 
The  metallic  case  containing  the  color -comparison  disc,  \'. 
T.  The  metallic  wing  that  receives  the  telescoping  camera 
tube  U,  and,  when  not  in  use,  rotates  eccentrically  into  place 
over  the  back  of  the  metallic  box  S.  U.  Telescoping  camera 
tube.  V.  Visible  portion  of  the  disc  that  carries  the  color- 
comparison  prism.  The  space  indicated  is  secured  by  cut- 
ting out  a  semicircular  piece  of  the  metallic  front,  S. 
Through  this  opening  the  light  passes  to  the  color-com- 
parison prism.  W.  White  glass  of  the  pipet.  X.  Pipet 
clamp.  Y.  Spring  damp  candle-holder.  The  leader  from 
Z  indicates  the  point  on  the  side  of  the  metal  case,  S,  where 
the  graduation  on  the  disc,  V,  is  visible,  and  where  the  read- 
ing is  taken. 
11. — Disc  Carrying  the  Color-comparison  Prism.  E.  Prism  of 
colored  glass.  F.  Semicircle  of  white  glass,  upon  the  edge 
of  which,  at  H,  is  etched  the  graduation.  I.  White  glass 
backing  the  color-comparison  prism,  E.  G.  Opening 
through  center  of  disc  to  receive  the  pivot  of  the  casing, 
which  acts  as  a  hub  around  which  the  disc  is  rotated. 


THK    HI.OOI). 


.^9  5 


opposite  to  tlie  former,  and  tlie  riders  are  added  to  complete  the  esti- 
mation. After  conii)letinj];  the  observation  the  same  care  is  re(|uisite 
in  cleaninij  the  instrument  as  already  advised  when  considering  the 
von  Fleischl  hem()j^l()]>inometer. 

Dare's  Hemoglobinometer.  In  this  instrument  the  undiluted  Itloofl, 
in  a  vor\"  tliin  la\cr,  is  coniparetl  with  a  glass  color-comparison  prism. 
The  principle  involved  is  in  some  respects  like  that  utilized  in  the  von 
Fleischl  instrument,  but  diflfers  in  the  fa<t  that  nurc  blood  is  used. 
The  accompanying  illustrations  (Figs.  210 
and  217)  explain  the  different  parts  of  the 
instrument. 

I'o  Mak'c  the  (  VKscrvaiio)!. — Before  draw- 
ing the  blood  the  instrument  should  be 
prepared  for  immediate  observation  by 
swinging  the  screen  (T,  Fig.  215)  outward 
and  attaching  the  camera  tube  (U,  Fig. 
216)  and  candle-holder  (Y,  Fig.  216).  The 
candle  should  be  pressed  into  the  holder 
at  such  a  level  that  the  wax  at  the  wick- 
end  will  be  on  a  level  with  the  top  of  the 
spring  clamp  that  holds  the  candle;  any 
cur\-e  in  the  candle-wick  should  be  so  turned 
that  its  convexity  faces  the  instrument, 
and  the  flame  should  be  in  line  with  the 
metal  shank  in  which  the  spring  clamps 
are  attached,  so  that  the  intensity  of  the 
candle-light  will  be  equally  divided  on 
both  the  blood  and  color-comparison  sides. 
As  the  comparison  should  be  made  as 
soon  as  possible  after  the  blood  has  been 
drawn,  a  means  of  lighting  the  candle 
should  also  be  at  hand.  The  pipet  for 
collecting  the  blood  (II,  Fig.  2 1 6.  X  W ;  Fig. 
217.  II)  is  removed  from  the  tongue  in 
which  it  fits;  the  milled  head  controlling 
the  screw  that  holds  the  two  pieces  of 
glass  (A.  B,  Fig.  217,  II)  is  turned  far 
enough  to  release  the  glass  plates;  these 
are  separated,  cleaned  with  alcohol,  and 
polished.  It  is  important  that  they  should 
be  free  from  all  foreign  substances,  and. 
above  all,  that  they  should  not  be  greasy. 
After  thorough  cleansing  they  are  returned 
to  their  proper  position  in  the  following 
manner:  The  observer  will  have  noticed 
that  one  of  the  glasses  (the  white  glass) 
a  thin  plate  of  glass,  which  extends  to  within  seven  millimeters  of  one 
end.  If  the  second  gla.ss  be  laid  upon  the  thin  plate,  a  space  is  forrned 
at  one  end  of.  and  between,  the  two  glass  plates.  This  is  the  capillar)' 
space,  into  which  the  blood  is  to  be  received;  it  is  shown  at  I),  hgure 
217.  The  glass  plates  are  placed  in  the  clamp  with  the  end  containing 
the  space  projecting  outward,  and  are  secured  in  this  position  by  tight- 


Fir..  217.— Dark's  HKMor.i.>BiNoMFTi  k 
I. — Horiznnlal  Section.  VirueJ  from  A b<r.f. 
J.  Candle  in  sprinKilamp.     K.  Whili- 
({I.ISS  on  ihc  l.aik  of   the  prism.     I.. 
The  colored  prism   ust-d  for  com  pari 
s<in  with  the  IiI.xhI.  and  sliown  al  I",  in 
liKuro  316.     -M.  The  oprninR  ilir.iu-! 
which  the  IJckxI  is  viewe<l.     -M'     I  !> 
oix-ninK  through  which  the  ci>n.i..in 
son   color    is  visible.      N.    The    tele 
scopinK  camera  tul)e.  through  which 
tlic    two   apertures,    M'   and  M.    .ir-- 
viewifl    in    making    the    comi-n      • 
O.    TransfKirent    Rlass    of   thr 
P.  White  glass  of  ill.- pii- I       I'. 
the  transiKirent  kI 
glass.  P.  is  the  c.v; 
ing  the  liKxxl.     "J 

lerixise.l  In-lwiH-n  the  hli-,-i  I'ljAt  jltd 
the  lomiKirison  c<4or. 
Aulomalu  I'ipfl.  —  \.  NMiitc  glo-V*. 
U.  Clear  gl.i.vs.  C  Piiwt  ilamp  in 
which  at  C  is  a  gn><)ve  into  which 
the  l.'iifciue   .'n    ll"-    -\M'     -!i!. 

<er 

sllfli-  ,  , 

contriJlinji  llie  .mTcw   11:^1  clan-, 
gl.a»sc». 


has    cemented    upon    it 


II. 


i> 


396  SPECIAL    PATHOLOGY. 

ening  the  retaining  screw  by  means  of  the  milled  head.  The  white 
glass  should  be  on  the  side  next  to  the  milled  head.  The  clamp  with 
the  two  glass  slips  is  as  shown  at  II,  figure  217.  The  instrument  is 
now  ready  for  use. 

The  finger-tip  or  the  lobe  of  the  ear  is  prepared  in  the  usual  way,  and 
the  blood  is  drawn  as  already  directed  (p.  385).  The  free  end  of  the  glass 
slips  (A,  Fig.  217,  II)  is  now  presented  to  the  drop  of  blood,  which 
at  once  enters  and  fills  the  capillary  space,  D,  figure  217.  If  the 
instrument  has  been  properly  cleansed,  the  pipet  at  once  fills  to  all  its 
margins.  Care  must  be  taken  to  prevent  the  blood  from  flowing  over 
the  glasses,  but  in  case  such  an  accident  occurs,  the  excess  of  blood 
can  be  readily  wiped  off.  The  clamp  is  at  once  placed  in  position,  as 
shown  at  X,  figure  216.  When  properly  placed,  the  projecting  glasses, 
with  their  intervening  capillary  space  filled  with  blood,  rest  over  the 
opening  shown  at  M  in  figure  217.  In  this  same  sectional  view  the 
glasses  are  shown  at  O,  P;  the  white  glass  is  at  P,  the  clear  glass  at 
O,  and  between  them  is  the  blood.  Light  the  can-die,  which  has  al- 
ready been  placed  in  its  proper  position.  The  eye  is  placed  to  the 
drawn-out  telescoping  tube  (U,  Fig.  216;  N,  Fig.  217;  in  both  instances 
the  eye  occupies  the  position  of  the  Roman  numeral  I  in  the  illustra- 
tions), and  the  line  of  vision  is  directed  toward  a  dark  surface,  with 
no  intervening  light,  either  direct  or  reflected,  except  that  afforded 
b}'  the  lighted  candle.  Absolute  darkness,  such  as  is  necessary  for  the 
von  Fleischl  instrument,  is  not  required.  A  dark  room  is  to  be  preferred ; 
bright  light  is,  of  course,  to  be  excluded,  and  the  direction  of  the  line 
of  vision  should  at  least  be  toward  a  lusterless  black  surface,  such  as 
is  ordinarily  aft'orded  by  a  black  coat.  Looking  through  the  tube  N, 
figure  217  (the  instrument  being  held  as  shown  in  Fig.  217,  in  which 
case  the  eye  would  be  at  I),  the  observer  sees  at  the  bottom  of  the 
tube  two  apertures  (M  and  M',  Fig.  216),  through  each  of  which  a 
more  or  less  faint  red  or  reddish-yellow  light  is  seen.  By  referring  to  the 
diagram,  figure  217,  it  will  be  apparent  that  the  light  coming  from 
the  candle,  J,  passes  through  the  blood  between  the  glasses,  P  and  O, 
and  is  visible  at  M.  Other  rays  of  light,  starting  from  the  same  point, 
pass  through  the  glass  comparison  prism  L,  and  are  to  be  seen  at  M'. 
The  two  apertures,  M  and  M',  are  closely  approximated;  the  milled 
head  R  (Fig.  216)  is  now  turned  one  way  or  the  other  until  the 
light  passing  through  the  glass  comparison  prism  and  visible 
at  M'  is  of  the  same  color  as  the  light  coming  through  the  blood  and 
presenting  at  M.  During  all  the  manipulation  the  graduation  has  not 
been  seen,  unless  the  observer  went  out  of  his  way  to  examine  it;  when 
the  two  colors  have  been  matched,  the  reading  is  made  on  the  side  of 
the  instrument,  just  behind  the  leader  from  the  letter  Z.  The  gradu- 
ation, as  in  the  other  hemoglobinometers,  is  in  percentage  of  the  nor- 
mal; its  location  on  the  disc  is  indicated  at  H,  figure  216,  II.  The 
reading  should  be  made  at  once  on  filling  the  pipet,  as  after  a  few  minutes 
contraction  and  shrinking  of  the  clot  occur,  giving  rise  to  a  marginal 
illumination  with  concentration  of  the  colored  elements  near  the  cen- 
ter, and  thereby  offering  certain  possibilities  of  error. 

When  the  observation  is  completed,  the  clamp  X,  figure  216,  is 
removed,  and  the  milled  head  is  turned  just  enough  to  release  the 
two  glass  slides,  which  are  separated  and  at  once  cleaned.     The  ease 


TlIK    HI.OOD.  397 

■with  which  the  onl\-  part  soiled  is  cleansed  contrasts  with  the  great 
dithcultv  ordinarily  attending  efforts  satisfactorily  to  clean  the  auto- 
matic pipets  and  mixing  chambers  of  the  instruments  devised  by  von 
Fleischl  and  Oliver. 

Estimation  of  the  Quantity  of  Hcnioiilobiii  hy  the  Specific  Gravity. — 
As  a  rule,  the  specific  gravity  of  the  blood  indicates  with  a  fair  degree 
of  accuracv  the  quantity  of  hemoglobin  present,  and  hence  may  be  util- 
ized as  one  of  the  methods  for  hemoglobin  estimation.  As  alteration  in 
the  densitv  of  the  plasma  can  not  be  ignored,  and  as  possible  hydremia 
can  not  be  overlooked,  the  specific  gravity  method  will  always  be  open 
to  sources  of  error.  In  diabetes  the  evident  high  specific  gravity  (not 
uncommonlv  toOo  or  over)  would  be  misleading;  under  such  condi- 
tions the  method  is  not  applicable.  Influences  increasing  the  density 
of  the  blood  by  abstracting  the  water,  thereby  raising  the  plasmatic 
specific  gravity,  vitiate  the  results  obtained  by  this  method.  The 
following  table,  from  Hammerschlag,  gives  the  hemoglobin  value  of 
specific  gravities  between  1033  and  1060: 


specific  Gravity. 

Hemoglobin. 

Specific  Gravity. 

Hemoglobin. 

IO33-IO35 

25-30 

per  cent. 

104S— 1030 

55-65 

per  cent 

1035-103S 

30-35 

" 

1050-1053 

65-70 

IO3S-IO40 

35-40 

'* 

1053-1055 

70-75 

" 

IO40-IO45 

40-45 

'  * 

1055-1057 

75-S5 

" 

IO45-IO4S 

45-55 

** 

1057-1060 

85-05 

** 

To  Deter)}!  i lie  the  Specific  Gravity. — The  simplest  procedure  for  deter- 
mining the  specific  gravity  of  the  blood  is  the  benzol-chloroform  method 
of  Hammerschlag.  Chloroform  possesses  a  specific  gravity  much  higher 
than  blood  (1525),  benzol  much  lower  (08S9),  and  as  the  two  fluids  are 
miscible  in  all  proportions,  any  intermediate  specific  gravity  is  readily 
obtained.  The  instruments  needed  are  a  urinometer  or  hydrometer 
iar  and  an  accurate  urinometer,  the  scale  of  which  should  reach  at  least 
1060.  A  mixture  of  chloroform  and  benzol  is  made  having  a  specific 
gravitv  of  about  1060;  the  blood  is  obtained  in  the  usual  manner  and 
is  drawn  into  a  capillary  tube,  such  as  the  Thoma-Zeiss  pipet  or  Gowcrs' 
pipet,  or  similar  tube;  care  must  be  taken  that  no  air  is  permitted  to 
enter  the  column  of  blood.  From  the  pipet  a  drop  is  gently  and 
slowly  ejected  into  the  chloroform-benzol  mixture,  being  careful  to 
exclude  air.  If  the  hydrometer  jar,  containing  the  chloroform-benzol 
mixture,  has  been  properly  cleansed  and  dried,  the  drop  of  blood  will 
not  adhere  to  its  wall.  The  blood,  not  being  miscible  with  the  reagents, 
forms  a  drop,  which  floats  on  the  surface  of  the  fluid.  Benzol  is  added, 
with  careful,  repeated  stirring;  the  addition  is  continued  until  a  den- 
sity is  reached  in  which  the  drop  neither  rises  to  the  top  nor  sinks  to  the 
bottom;  in  other  words,  the  specific  gravity  of  the  fluid  is  made  the  same 
as  the  specific  gravity  of  the  drop  of  blood.  The  specific  gravity  of  the 
fluid  is  now  taken,  and  the  result  obtained  is.  of  course,  the  specific 
gravitv  of  the  blood.  From  this  specific  gravity  the  percentage  of 
hemoglobin  mav  be  calculated. 

Tallqvisfs  Hemoglobin  Scale. — A  very  simple,  but  only  approxi- 
matelv  accurate,  mctliod  of  estimating  the  hemoglobin  is  furnished 
by  this  device,  the  essential  features  of  which  are  a  color  scale  forming 
one  leaf  of  a  book,  the  remaining  leaves  being  absorbent  paper.     A 


398  SPECIAL   PATHOLOGY. 

small  square  of  the  latter  is  touched  to  a  blood-drop  and  the  resulting 
spot  compared  with  the  scale. 

Remarks  on  Hemoglobin  Methods. — Of  the  various  methods  given, 
that  devised  by  von  Fleischl  has  received  most  general  acceptance. 
It  is  said  that  the  von  Fleischl  instrument  is  unreliable  for  very  low 
percentages  of  hemoglobin;  the  source  of  error  is  best  met  by  using 
two  measures  of  the  blood,  secured  by  filling  two  pipets  and  emptving 
both  into  the  mixing  chamber.  The  resulting  reading  is  halved.  Yar- 
row and  Kitchens'  have  compared  results  obtained  bv  the  specific 
gravity  method,  by  Gowers',  von  Fleischl's,  and  Oliver's  instruments, 
and  by  the  hematoscope  of  Henocque,  and  after  an  exhaustive  investiga- 
tion these  authors  conclude  that  the  instrument  of  Oliver  is  by  far  the 
most  accurate.  Next  to  this  method  they  prefer  calculations  based  upon 
the  specific  gravity,  and  look  upon  von  Fleischl's  and  Gowers'  instru- 
ments as  constantly  liable  to  error.  Dare's  instrument,  because  of 
the  ease  with  which  it  is  operated  and  cleaned,  the  lack  of  possible  error 
by  diluting  the  blood,  and  high  degree  of  accuracy,  is  one  of  the  most 
satisfactory  of  the  hemoglobinometers  now  available  for  general  use. 
The  author  is  impressed  by  the  fact  that  two  individuals  can  read  so 
close  together,  variations  of  two,  three,  four,  and  five  per  cent,  being 
infrequent.  The  same  workers  will,  in  reading  the  von  Fleischl  and 
Oliver  instruments,  differ  to  the  extent  of  from  five  to  ten  per  cent. 
For  physicians  to  whom  one  of  the  more  accurate  but  expensive  instru- 
ments is  not  accessible  Tallqvist's  scale  furnishes  valuable  information. 
The  cost  is  merelv  nominal. 

The  term  percentage  of  hemoglobin  means  the  percentage  of  the 
normal.  If  the  reading  is  loo,  the  hemoglobin  is  normal;  if,  however, 
the  reading  is  So,  there  is  eighty  per  cent,  of  the  normal,  or  twenty  per 
cent,  less  than  normal;  if  the  reading  is  120,  there  is  twentv  per  cent, 
more  than  in  health. 

The  color-index  is  the  relative  richness  of  each  erythrocvte  in 
hemoglobin.  As  previously  stated,  the  percentage  of  hemoglobin 
estimated  by  .the  instruments  commonly  at  hand  is  the  percentage 
of  the  normal.  If  in  a  blood  examination  we  find  5,000,000  red  blood- 
cells  and  100  per  cent,  of  hemoglobin,  it  is  evident  that  both  the  erythro- 
cytes and  the  hemoglobin  are  normal,  and  the  color-index  is  i.  If, 
however,  the  blood  contain  2,500,000  red  blood-cells  and  50  per  cent, 
of  hemoglobin,  it  is  evident  that,  while  there  is  a  great  reduction  in  red 
blood-cells,  there  is  also  a  proportionate  reduction  in  hemoglobin;  it  is 
thus  seen  that  the  corpuscular  richness  of  the  cells  present  is  the  same 
as  in  health,  therefore  the  color-index  is  normal — i.  If,  on  the  other 
hand,  as  in  chlorosis,  4,000,000  red  blood-cells  are  present  (assuming 
as  before,  for  convenience  in  calculation,  that  the  normal  is  5,000,000), 
then  the  number  of  erythrocytes  present  is  80  per  cent,  of  the  normal. 
If  the  blood  shows  the  presence  of  50  per  cent,  of  the  normal  amount 
of  hemoglobin,  it  is  evident  that  the  hemoglobin  is  much  more  reduced 
than  the  erythrocytes;  in  other  words,  the  color-index  is  low.  The 
exact  color-index  is  obtained  by  dividing  the  percentage  of  hemoglobin 
by  the  percentage  of  erythrocytes:  in  the  instance  given,  |-|,  or  f  (or, 
in  decimals,  0.625),  would  be  the  color-index.     From  the  foregoing  it 

'  "University  Medical  Magazine,"  October,  1899. 


TiiK  HI, (ion. 


399 


will  be  seen  that  the  color-index  may  he  worked  out  h\-  the  following 
formula : 


PiTccnlauc  of  hrmnKldhin 
PtTccnugc  of  erythrocytes 


I  Hi'  'F    IIHRX. 


COUNTING   BLOOD-CELLS. 

The  Red  Cells.  1  he  I  Iwnui-Ziiss  Ihiiiocytoiiictcr. — This  apparatus 
consists  of: 

1.  A  capillary  tube  of  glass,  about  fifteen  centimeters  lonj^',  exj)and- 
ing  in  the  upper  portion  into  a  bulb,  in  which  lies  a  small  glass  ball 
(Fig.  219).  The  lower  portion  of  the  tube  is  graduated  in  tenths,  from 
0.1  to  I,  while  just  above  the.  mixing  chamber  is  the  mark  loi,  indi- 
cating that,  if  filled  with  blood  to  the  mark  i,  and  then  with  some  other 
fluid  to  loi.  the  fluid  above  the  point  i  will  represent  a  dilution  of  i 
part  in  100. 

2.  A  counting  chamber,  composed  of  a  heavy  glass  slide,  the  center 
of  which  is  formed  into  a  circular  cell  by  a  rim  of  glass;    in  the  middle 


•      R0CMtStt1l,H.Y 


\> 


\. 


Fic.  21S.— Thoma-Zeiss  HtMocYTOSCETER. 

.■Vs  shown  in  the  illustration,  the  ilifferont  parts  are  packed  in  a  velvet  linej  case  for  safe  transportation.  In  the 
center  of  the  ca-sc  is  a  Rla.^s  slide,  which  contains  the  ci  unting  chamlH-r.  .Vs  illu.strated.  the  two  pipcts— one  for 
the  crythrfKvtcs  and  one  for  the  leukocytes —are  contained  in  the  singh-  •  ■-  I  ''•■  >■'  ■  •  "'  "  '■  <•<<"  ''"•  V  ■  .n'  rs 
is  just  under  the  center  of  the  slide. 


of  the  cell  is  a  circular  glass  platform.  (See  A  and  C,  Fig.  221.)  When 
a  cover-glass  is  placed  over  the  cell,  the  space  between  the  cover-glass 
and  the  surface  of  the  counting  platform  is  o.i  mm.  The  counting 
platform  has  on  the  center  a  space  ruled  in  sciuares,  the  side  of  each 
square  being  .^'j  of  a  millimeter.  The  cubic  capacity,  then,  of  the  space 
surrounded  l)v  each  ruling  and  covered  by  the  cover-glass  is  equal  to 
.I'ij  mm.  X  r},',  mm.  X  iV^Tini--  or  xitVit  o*  '^  cubic  millimeter.  The  small 
moat  between  the  platform  and  the  rim   receives  the  overflow  of  fluid. 

A  puncture  is  made  in  the  finger  or  in  the  lobe  of  the  ear,  as  already 
directed,  and  the  blood  is  sucked  into  the  cai)illary  tube  until  it  reaches 
the  mark  0.5;  after  wiping  the  end  of  the  tube  in  order  to  remove  the 
excess  of  blood,  a  three  per  cent,  salt  solution,  or  other  acceptable  dilut- 
ing fluid,  is  drawn  into  the  tube  until  the  fluid  has  risen  to  the  point 
marked  loi,  giving  a  dilution  of  r  to  200.  This  is  preferable  to  using 
the  mark  i  for  the  blood,  with  a  consefjuent  dilution  of  i  to  100.  as  it 
avoids  the  danger  of  drawing  the  blood  into  the  bulb  of  the  pipet.     In 


400 


SPECIAL  PATHOLOGY. 


101 


order  to  secure  absolute  control  of  the  blood  and  diluting  fluid,  Galli^ 
has  devised  the  mixing  tube  shown  in  Fig.  220.  The  vacuum  causing 
the  blood  to  enter  the  pipet  is  produced  by  turning  the  screw  (/).  To 
aspirate  the  diluting  fluid  more  rapidly,  'the  sliding  jacket  carrying 
the  piston  {d)  is  elevated  as  shown  in  the  small  figure.  This  instru- 
ment, while  unquestionably  permitting  a  greater 
degree  of  accuracy  than  does  the  Thoma-Zeiss,  would 
appear  to  be  less  readily  manipulated.  The  contents 
of  the  tube  being  thoroughly  mixed  by  shaking,  the 
fluid  below  the  bulb  is  then  expelled,  the  point  of 
the  tube  is  wiped,  and  a  drop  of  the  diluted  blood  is 
placed  on  the  ruled  platform  of  the  counting  chamber; 
a  cover-glass  is  then  cautiously  laid  upon  the  drop, 
care  being  taken  that  the  cover  does  not  shp  to 
either  side.  If  a  globule  of  air  forms  between  the 
cover  and  the  counting  platform,  the  cell  and  cover 
should  be  cleaned  and  the  attempt  should  be  re- 
peated, the  cover-glass  being  so  adjusted  that  there 
are  no  air-bubbles  present.  The  preparation  should 
be  rejected  if  the  liquid  makes  its  way  between  the 
cover-glass  and  the  external  rim.  The  cover-glasses 
used  in  ordinary  microscopy  are  not  suited  for  use 
with  this  instrument;  they  are  rarely  flat,  cup  easily, 
and  in  either  case  may  give  misleading  results.  Only 
the  heavy  covers  that  accompany  the  instrument 
should  be  used.  The  thick  cover-glass  and  the  depth 
of  the  cell  preclude  the  use  of  high-power  lenses ;  the 
most  convenient  lens  for  the  count  is  a  ^-inch  ob- 
jective, but  a  i-inch  or  ^-inch,  with  good  working 
distance,  may  be  employed.  When  purchasing  a 
microscope,  the  buyer  should  specify  that  the  medium 
power  objective  possess  sufficient  working  distance — 
space  between  lense  and  top  of  'cover-glass — for  this 
purpose.  The  microscope  is  so  adjusted  that  the 
stage  is  perfectly  level.  The  slide  is  placed  upon  the 
stage  and  the  ruled  areas  are  found  and  centered  by 
the  use  of  a  i-inch  or  a  -l-inch  objective.  The  medium 
power  (j-inch  objective)  is  now  thrown  in  the  optic 
axis  of  the  instrument,  and,  without  looking  through 
the  eye-piece,  the  objective  is  racked  downward  until 
it  almost  touches  the  cover-glass.  The  eye  is  then 
placed  at  the  eye-piece  and  the  illumination  is  per- 
fected, after  which  an  accurate  focus  is  secured  by 
slowly  focusing  upward.  At  first  the  corpuscles  may 
be  in  different  focal  planes,  and  it  is  therefore  best 
to  allow  the  instrument  to  remain  quiet  for  a  few 
minutes  until  the  cells  have  been  deposited  upon  the 
counting  platform.  The  cells  should  be  evenly  distributed,  as  shown 
at  B  in  figure  221.  If  they  are  clumped  and  not  uniformly  distributed 
over  the  counting  platform,  the  mixing  has  been  inefficient,  and  the 
mixing  tube  must  be  cleaned  and  the  whole  process  repeated.  Count 
'"Munch,  med.  Woch.,"  51,  No.  13,  March  29,  1904. 


Fig.  219.  —  Capillary 
Mixing  Tube  of 
THE  Thoma  -  Zeiss 
Apparatus. — 
{Jaksch.) 


THE   BLOOD. 


401 


the  corpuscles  in  at  least  So  scjuares,  using  5  blocks  of  16  each  con- 
tained within  double  lines;  these  blocks  should  be  selected  from  various 
parts  of  the  ruled  area  in  order  most  nearly  to  obtain  a  mean  of  the 
entire  specimen.  Clean  the  counting  chaml)er.  place  in  it  a  fresh  drop 
of  the  diluted  blood,  and  repeat  the  count,  using  the  average  of 
the  two  in  computing  the  total.  These  two  counts  will,  in  normal 
blood,  yield  about  1000  cells,  a  number  guaranteeing  sutlicient  accuracy. 
To  obtain  the  total,  multiply  the  number  of  cells  counted  bv  the  degree 
of    dilution    and    by    4000 

(lAiT  c.mm.  being  the  con-  ^^rs^^^^tm 

tents  overlying  a  square),         a   5'""      '        .  ^ 

and  divide  by  the  num- 
ber of  squares  counted. 
Example:  A  count  gives 
490  red  cells  in  80  squares ; 


200 

S3 


4,qoo.ooo, 


Fic.  223.— .MixisT.  Ti  BE  or  GAI.1.1. 


lie.     221. COUNTI.SG     ClIAUBF.R     OF    THE      THOIIA-ZEISS 

HEMOCyTOMETER. — (Llndois.) 

.\.  Si'ctional  view.     On  the  upper  surface  is  shown  . 
position,     beneath  the  center  of  the  cover  is  .t  >;: 
upon    which    is    ruleil     the    division.s    shown    in 
view,  C.     The  space  between  the  cover  an<l  the  rv 
is  0.1  mm.     On  each  side  of  the  ruled   platform 
moat    that    prevents  the  fluid    from  rcarhin.;  r' 
upcin  which  the  co\er  kLis-  rests.      H.  \\i\' 
surface  under  miiTi)s»ii|n-  .md  showing  uin 
the  red  tells  as  I  hey  should   appe.ir  in    i 
dilution. 


the  number  of  cells  in  one  cubic  millimeter  of  l>lood.  It  will  readily 
be  seen  that  if  490,  the  number  of  cells  counted,  be  eliminated  from 
this  formula,  the  remaining  numbers,  200  X  400  -^  80.  will  give  10.000. 
Hence  if  this  degree  of  dilution  and  num]»er  of  sijuares  be  employed 
in  each  count,  the  problem  is  reduced  to  multii)lying  the  number  of 
cells  counted  by  10,000;  this  is  simply  annexing  four  cij)hers.  and  the 
total  is  thus  olitained  instantly  without  computation.  In  recording 
the    corpuscular    rii  hnc^s    ('t'rvt1ir(n\tes    or    leukocytes)    of    the    blood 

27 


402  SPECIAL   PATHOLOGY. 

it  is  customary  to  give  simply  the  number  without  stating  the  quantity 
of  blood — e.  g.,  "  4,900,000  red  cells"  means  that  that  number  was 
found  in  one  cul)ic  millimeter  of  blood. 

Counting  White  Corpuscles. — To  count  the  white  corpuscles  in  a 
dilution  such  as  that  used  for  the  red  would  require  more  time  and  a 
much  larger  ruled  space  than  is  available  in  the  Thoma-Zeiss  instrument. 
For  this  reason  a  lower  dilution  is  used, — i  :20,  instead  of  i  :20o, — and, 
for  diluting,  a  0.33  per  cent,  solution  of  acetic  acid,  which  destroys  the 
red  blood-cells,  at  the  same  time  making  the  white  cells  more  distinct. 
The  entire  field  of  400  squares  should  be  counted  in  at  least  two,  and 
better  three  or  four,  drops.  The  method,  with  the  foregoing  exceptions, 
is  as  given  for  the  red;  in  the  calculation,  20  is  substituted  for  200  and 
400  for  80.  The  constant  factor  in  such  formula  will  be  200,  and  this 
mav  be  used  for  multiplying  the  number  of  leukocytes  counted,  in  the 
manner  that  10.000  is  employed  for  the  red  cells.  Better  than  the 
Thoma-Zeiss  chamber  for  counting  the  leukocytes,  however,  is  the 
Zappert,  or,  if  preferred,  one  of  the  many  still  more  elaborately  ruled 
stages,  in  which  eight  additional  large  squares  surrounding  the  one 
representing  the  older  pattern  are  made  available.  Counting  the  entire 
nine  squares,  gives  the  equivalent  of  3600  of  the  small  squares,  and 
one  filling  of  the  counting  chamber  suffices.  With  such  a  chamber 
the  leukocytes  may  be  counted  in  the  mixture  employed  for  enumerating 
the  red  cells  if  either  of  the  following  diluting  solutions  be  used : 

Toisson's  Solution. 

Methyl-violet 0.025  g"^. 

Sodium  chlorid, i.o 

Sodium  sulphate 8.0 

Glycerin 30.0       c.c. 

Distilled  water 160.0 

Sherrington's  Solution. 

Ehrlich's  purified  methjdene-blue,  .• o.i       gm. 

Sodium  chlorid 1.2 

Neutral  potassium  oxalate 1.2 

Distilled  water, 300.0 

The  anilin  dyes  contained  in  these  solutions  stain  the  leukocytes, 
and  therebv  make  possible  their  enumeration.  A  stain  may  also  be 
added  to  other  diluting  fluids. 

Cleaning  the  Hemocytometer. — In  every  instance  this  should  be 
done  as  soon  as  the  count  is  completed.  The  counting  chamber  must 
be  cleaned  with  water  only,  and  this  should  not  be  hot;  otherwise 
the  cement  holding  the  rim  of  glass  will  be  softened.  Various  methods 
for  cleaning  the  pipets  are  recommended,  most  of  them  making  use 
of  water,  alcohol,  and  ether  in  the  order  named.  The  simplest  and  by 
far  the  best  plan  is  to  remove  the  rubber  tube  and  expel  the  contents 
of  the  pipet  by  means  of  a  small  ear  syringe  fitted  over  the  end.  Keeping 
the  bulb  compressed,  the  free  end  of  the  pipet  is  immersed  in  water 
and  the  bulb  allowed  slowly  to  expand,  thus  filhng  the  pipet,  which 
in  this  manner  is  washed  twice  with  water  and  twice  with  alcohol. 
It  is  then  dried  by  warming  over  a  Bunsen  burner  sufficiently  to  vaporize 
the  alcohol.  This  can  be  done  without  endangering  the  instrument 
if  it  be  kept  constantly  rotating  and  is  tested  by  the  fingers  to  guard 


Till-;    Hl.( )()!). 


40.? 


aj^ainst  ()vorheatinl,^      X'aiiorizalioii  is  yidcil  by  occasionally  forcinj,'  air 
throiii^h  tlu"  pipi't  wiih  tlio  bull). 

Differential  Counting. —  Dried  and  fixed  films  arc  stained  hv  Khrliih's 
or  Wriiiht's  stain,  and  mounted  as  already  direeted.  Then  the  leuko- 
cytes are  counted  by  traversinj,'.  in  straight  lines,  more  or  less  of  the 
stained  field,  carefully  avoiding:;  i^oin^  over  the  same  point  twice  and 
countinj,'  at  least  500  leukocytes.  A  mechanical  sta^e  greatly  facilitates 
the  count.  On  a  piece  of  paper  by  the  side  of  the  microscope  are  ar- 
ran^'cd  columns,  at  the  top  of  which  are  written  the  forms  of  leuko- 
cytes;   after   counting   the   required    number,    the   columns   are  added 


AiUUh|iiii|iin|ini|iiH|Mmiiliiiiil|mi| 


Fn;.  2i;. — Hkmatocrit  Tiuk.     i  Iwui.    iniur.il     i. . 
The  IuIh-  a.s  illustratc<i  ha.<  l>i-i-n  lillcd  with  IiIimmI  and  rotated,  as  dirorlcd  in  the  text,  until  the  crythrf>cyte»  have 
Cdlletlcd  at  one  end.  occupyinK  45  ilegrees  (or  (jraduation-marks).     This,  muhiplied  l>y  100.000,  gives  4.500.000 
— the  numl)cr  of  erythrocytes  to  the  culiic  niiilimeler  of  l)lood. 

and  the  percentage  of  each  form  present  is  calculated.  Differential 
counting  of  diseased  red  cells  is  sometimes  resorted  to,  and  mav  be 
done  in  the  same  manner. 

Hematocrit. — This  instrument  (see  cha])tcr  on  Examination  of  the 
Urine)  readily  enables  one  to  estimate  the  I'oliinw  oj  the  red  corpuscles. 
It  consists  of: 

1.  Two  glass  tubes,  50  mm.  long,  with  a  lumen  of  0.5  mm.,  and 
graduated  into  100  parts.     (Fig.  222.) 

2.  A  metallic  frame  (Fig.  223),  in  which  the  glass  tubes  are  fastened 
— on  the  outer  side  by  a  metallic  cup  in  the  frame,  and  at  the  proximal 
extremity  by  a  spring,  which  is  attached  to  a  hollow  metal  cylimler, 


FlO.    71,^. —  ROTATINC.    pRANre    OF    TlIK    IIkMATOCRIT. 

The  tube  on  the  right  is  in  ijosilion;  the  tul)c  on  the  left  shows  the  graduation  and  the  direction  which  the  smnllrr 
end  should  take  when  in  |iosition.  The  entire  metiJ  frame  is  to  l)e  placed  on  the  vertical  suplirtrt,  .is  described 
in  the  chapter  on  Kxamination  of  the  I'rine. 


which  projects  downward  from  the  center  of  the  frame,  and  by  means 
of  which  the  frame  can  be  made  to  rotate  on  a  vertical  axis.  The 
cups  receiving  the  ends  of  the  glass  tubes  contain  rul)ber  washers  that 
also  act  as  cushions. 

3.  A  vertical  support,  which  can  be  made  to  rotate.     A  sj>eed  of 
at  least  10,000  rotations  a  minute  is  necessarv. 

4.  A  metallic  box,   to  be  fastened  to  a   table,   and  containing  the 
machinery  by  which  the  vertical  support  is  rotated. 

To   Use  the   Hematocrit. — ( )ne   of   the   graduated    tubes,   previously 
well  cleaned,  is  attached  by  means  of  a  short  piece  of  pure  rubl^er  tubing 


404 


SPECIAL  PATHOLOGY. 


to  a  medicine-dropper.  The  bulb  of  the  dropper  is  gently  compressed, 
and  the  end  of  the  graduated  tube  is  presented  to  the  escaping  blood; 
the  compressed  bulb  of  the  pipet  is  slowly  released,  thereby  sucking 
the  blood  into  the  capillary  tube.  As  soon  as  the  tube  is  full,  the 
end  in  the  drop  of  blood  is  pressed  against  the  patient's  thumb  or 
other  surface  from  which  the  blood  is  being  obtained,  without  with- 
drawal from  the  drop,  and  the  rubber  tube  and  the  medicine-dropper 
are  detached  from  the  hematocrit  tube.  Figure  224  and  the  legend 
explain  the  usual  method  by  which  the  tube  is  filled.  If  but  one  tube 
is  to  be  filled,  the  other  should  be  in  place  in  the  rotating  frame  of 
the  instrument,  to  act  as  a  counterpoise  to  the  charged  tube.  As  soon 
as  the  latter  is  filled,  it  is  placed  in  position  in  the  frame,  which  is  at 
once  rotated  at  the  rate  of  10,000  revolutions  a  minute  for  two  minutes. 
The  red  blood-corpuscles  collect  in  the  distal  extreinity  of  the  tube, 
the  leukocytes  near  the  center,  and  the  liquor  sanguinis  in  the  proximal 
portion.  Find  the  number  of  degrees  the  red  cells  occupy,  and,  as 
each  degree  represents  approximately  100,000  cells  to  the  cubic  milli- 
meter, the  addition  of 
^  ^  five  ciphers   gives   the 

number  of  red  cells  to 
the  cubic  millimeter. 
Thus,  if  the  red  cells  oc- 
cupy fifty  graduations 
on  the  scale,  there  are 
5,000,000  red  cells  to 
the  cubic  millimeter. 
(See  Fig.  222.) 

It  is  apparent  that 
the  result  is  in  volume 
of  red  cells,  and  not  the 
number  that  must  be 
obtained  by  a  calcula- 
tion which  does  not 
take  into  consideration 
the  size  of  the  cells. 
"When  the  red  cells  are  larger  than  normal  the  greater  volume  would 
give  a  misleading  result.     The  reverse  is  equally  true. 

Volume  Index. — The  use  of  the  hematocrit  in  conjunction  with  the 
hemocytometer  makes  possible  the  determination  of  the  volume  index, 
which  indicates  the  volume  of  the  individual  red  cell  as  the  color  index 
represents  its  hemoglobin  content.  It  is  obtained  by  dividing  the  per- 
centage volume  of  the  red  cells  by  their  percentage  number.  Example : 
If  the  column  of  red  cells  in  the  hematocrit  reaches  45  instead  of  50,  the 
normal,  the  percentage  volume  is  90;  if  the  count  be  4,000,000,  the  per- 
centage number  is  So;  90-^80=  1.125,  the  volume  index. 

Coagulation  Time. — No  reasonably  satisfactory  method  for  deter- 
mining the  coagulation  time  of  the  blood  has  been  devised.  The  sim- 
plest is  that  of  Milian,  which  consists  in  placing  a  large  drop  of  blood 
upon  a  clean  glass  slide,  the  latter  being  tilted  toward  a  vertical  plane 
after  the  lapse  of  a  few  minutes  to  determine  if  the  shape  of  the  drop 
is  thereby  changed.  During  the  time  it  is  fluid,  this  manipulation 
causes  the  drop  to  assume  a  pear  shape;  when  coagulation  has  occurred, 
tilting  does  not  change  the  outline  of  the  drop.     Normally,  coagulation 


Fig.  224. — A  Method  of  Filling  the  Centrifuge  Tube. 
The  hand  of  the  patient.  The  thumb  has  been  punctured  and  is 
tirmly  supported  by  the  left  hand  of  the  operator,  as  shown  at  B. 
C ■  The  right  hand  of  the  operator,  holding  the  capillary  tube,  to 
which  is  attached  a  rubber  tube,  D.  To  the  latter  suction  is  applied, 
thereby  drawing  the  blood  up  into  the  capillary  tube.  By  some  work- 
ers this  method  is  preferred  to  that  recommended  in  the  text. 


Till-:  Hi.ooi).  405 

is  said  to  occur  in  live  minutes;  i)crsonal  oliscrvations  indicalf  lliat 
a  considerably  Ioniser  time  is  usually  rc(|uired.  The  hemogelometer 
of  Hitfi  skives  ])roniisc  of  lioini,^  a  valuable  device.  Essentially  it  is  a 
large  glass  tube  closed  liy  a  doublx-  perforated  stoj^jjer  which  transmits 
a  tlicrmometer  anil  a  glass  rod.  I'rom  the  lower  end  of  the  latter 
projects  a  ])latinum  wire  bearing  a  series  of  loops  which  can  be  lowered 
into  the  water  half  tilling  the  tube.  These  loops  are  in  succession 
touchetl  to  drops  of  blood,  and  after  a  few  minutes  are  at  regular  inter- 
vals immersed  by  lowering  the  wire.  Coagulation  is  shown  when  a 
drop  fails  rapidly  to  diffuse  in  the  water,  ordinarily  in  from  seven  to 
ten  minutes. 

Wright's  coagulometer  is  one  of  the  more  elaborate  instruments, 
but  for  clinical  work  is  little,  if  any,  better  than  those  named,  one 
of  the  principal  objections  being  the  large  cpiantity  of  blood  recjuired. 
It  consists  of  a  set  of  heavy  glass  tubes,  with  a  ca|)illary  Vjore,  o]»en 
at  both  ends.  At  intervals  of  a  minute  the  tubes  are  partly  tilled 
with  blood  and  kept  at  body-temperature  by  immersion  in  water.  In 
succession  the  blood  is  forced  out  upon  white  paper  by  blowing  into 
the  tubes,  coagulation  being  shown  by  the  presence  of  a  capillary  clot. 
The  elapsed  time  since  that  particular  tube  was  tilled  is  the  coagulation 
time,  which  in  normal  blood  is  usuallv  from  four  to  seven  minutes. 


GENERAL  PATHOLOGY,  COMPOSITION,  AND  STRUCTURE  OF  THE  BLOOD. 

The  circulating  normal  blood  consists  of  a  fluid  portion  (the  liquor 
sanguinis)  in  which  are  suspended  the  solid  elements — the  blood-cor- 
puscles or  blood-cells.  The  licjuor  sanguinis  is  probably  identical — or 
practicallv  so,  at  least — with  the  circulating  medium  outside  the  blood- 
vessels in  the  primitive  lymph-spaces,  which  passes  to  the  lymph- 
nodes  and  is  returned  to  the  circulation.  As  a  part  of  the  blood, 
the  liquor  sanguinis  is  more  than  a  mere  vehicle  for  the  transportation 
of  the  solid  elements,  and  with  its  complex  chemistry  is  the  essential 
food-carrving  body  to  the  tissue  at  large.  It  is  composed  of  the  elements 
out  of  which  serum  and  Hbrin  may  be  formed;  and  while  this  separation, 
so  far  as  the  plasma  is  concerned,  is  largely  a  death  change,  still,  evidence 
is  not  wanting  to  show  that  tibrin  formation  may  be  an  essential  element 
in  the  protection  of  the  organism  and  in  repair.  Thus,  the  distinct 
wall  of  tibrin  that  forms  around  infected  areas  or  covers  an  infected 
serous  surface,  such  as  a  pleura,  and  through  which  osmosis  and  the 
absorption  of  bacterial  products  are  reduced  t(^  a  minimum,  acts  not 
onlv  as  a  scatTold  upon  which  embryonic  tissue,  ami  eventually  granula- 
tion tissue,  can  build  the  framework  which  is  to  rei)air  the  injured 
part,  but  also  as  a  ])ro])hylactic,  limiting  membrane,  through  whii-h 
infection  travels  only  with  the  greatest  diiliculty.  Again,  of  all  the 
structures  produced  within  the  body,  tibrin  offers  the  greatest  resistance 
to  manv  of  the  injurious  incidents  to  which  the  tissues  are  liable;  the 
constant  pressure  of  the  circulating  blood,  as  in  an  aneur\'sm.  may  lead 
to  atrophv  and  to  the  disappearance  of  bone,  unless  conditions  arise 
that  determine  the  intervention  of  a  wall  of  tibrin.  through  which,  not 
uncommonlv,  we  may  hope  for  a  cure.  The  exact  factors  that  enter 
into  the  chemistry  of  fibrin  formation  are  not  known;  although  the 
third  corpuscle  (blood-platelet)  seems  to  bear  some  causative  relation  to 


4o6  SPECIAL  PATHOLOGY. 

the   process,   the   character  and   extent  of  such   influence   remain   one 
of  the  unsolved  problems  of  physiologic  chemistry. 

An  excess  of  til)rin,  or,  more  truly,  of  fibrin-forming  elements,  con- 
stitutes hyperinosis — a  condition  present  in  pregnancy,  and  occasion- 
ally in  chlorosis  and  other  forms  of  anemia.  Hypinosis,  or  reduction 
in  the  fibrin-forming  elements,  is  sometimes  observed  in  leukemia  and 
pernicious  anemia.  In  addition  to  the  influences  modifying  the  amount 
of  fibrin,  there  are  marked  differences  in  the  rapidity  with  which  it 
is  formed.  As  a  rule,  intravascular  coagulation  begins  shortly  after 
death.  To  this,  however,  there  are  notable  exceptions.  The  author 
recalls  a  case  of  pernicious  anemia  in  which,  at  the  postmortem,  made 
twelve  hours  after  death,  the  blood  had  not  coagulated.  After  re- 
moval from  the  cardiac  cavities  a  quantity  collected  in  a  jar  for  later 
study  developed  a  satisfactory  coagulum.  The  blood  is  less  coagulable 
in  hemophilia,  in  which  disease  its  coagulability  may  be,  in  some  cases, 
increased  by  the  administration  of  calcium  salts,  while  in  other  cases 
the  local  application  or  the  internal  administration  of  these  agents 
fails  to  influence  the  condition.  Lessened  coagulability  is  present  in 
the  blood  after  death  from  poisoning  by  carbonic  acid  or  by  carbon 
monoxid  and  in  some  cases  of  asphyxia.  Snake-venom  and  bacterial 
products  lessen  the  coagulability  of  the  blood. 

Hydremia^  is  a  condition  in  which  the  blood  contains  an  excess 
of  water.  After  a  hemorrhage  the  volume  of  blood  is  made  up  by  the 
abstraction  of  fluid  from  the  tissues  at  large,  and  consequently  there  is 
a  more  or  less  temporary  hydremia.  When  it  is  reasonable  to  believe 
that  there  is  an  increased  amount  of  blood,  and  that  the  increased 
quantity  is  due  to  the  addition  of  water  or  saline  solutions,  as  after 
the  injection  of  a  large  quantity  of  normal  salt  solution,  the  condition  is 
called  hydremic  plethora.  Under  ordinary  conditions  hydremia  quickly 
disappears,  as  a  result  of  the  excretion  of  water  by  the  emunctories, 
particularly  the  kidneys. 

Anhydremia  is  the  reverse  of  hydremia.  The  lessened  amount  of 
water  present  in  the  blood  usually  results  from  its  rapid  extraction, 
although  it  is  conceivable  that  a  diminished  supply  would  induce  the 
same  condition.  The  concentration  is  usually  brought  about  by  the 
discharge  of  fluid  by  the  skin,  intestine,  or  kidney.  As  the  principal 
constituent  so  removed  is  water,  it  is  this  element  that  is  reduced.  As 
a  rule,  anhvdremia,  like  hydremia,  is  temporary.  In  the  former  con- 
dition the  tissues  quickly  supply  the  requisite  amount  of  fluid. 

In  a  number  of  morbid  conditions  the  blood-plasma  contains  ab- 
normal bodies  or  normal  constituents  in  abnormal  quantities.  A  small 
quantitv  of  fat  is  present  in  normal  blood;  occasionally,  however,  as 
in  alcoholism,  diabetes,  and  a  few  other  conditions,  it  may  be  markedly 
increased,  producing  a  condition  called  lipemia.  The  fat  may  be  recog- 
nized in  the  freshly  drawn  blood  as  small,  highly  refractile  granules 
which  not  uncommonlv  manifest  active  movement.  The  examination 
is  conducted  as  already  directed.  (See  p.  244.)  Dry  spreads  fixed 
in  osmic  acid  (pp.  i^T,  and  34)  will  show  the  blackened  fat  droplets. 
(See  also  Demonstration  of  Fat,  p.  244.)  The  serum  obtained  by  the 
centrifuge   may   contain   enough   fat   to   render   it   turbid.     The   small 

*  See  also  p.   261. 


Till-:    HLooI). 


40: 


<|uantity  of  glucose  iiornially  i)resent  in  tlie  Mood  is  markedly  imreased 
in  diabetes,  in  which  disease  it  may  be  jjresent  to  the  extent  of  0.7 
l^er  cent,  instead  of  the  normal,  o.i  17  ])er  cent.  An  increased  amount 
of  sugar  in  the  blood  is  called  glycemia.  In  leukemia,  in  pneumonia, 
in  some  forms  of  anemia,  and  at  times  in  liright's  disease  there  is  an 
increase  of  uric  acid.  or.  more  properly,  of  uric  acid  salts,  in  the  bloofl. 
In  gout  the  increase  in  urates  (uratemia)  is  sometimes  most  marked. 

The  presence  of  bile  pigments  in  the  blood  (cholemia)  is  the  essen- 
tial j)henomenon  of  jaundice  (p.  234).  Clinicians  recognize  a  form  of 
intoxication  which  has  long  been  termed  uremia.  At  one  time  this 
was  ])resumed  to  be  due  to  the  presence  of  an  excess  of  urea  in  the 
blood.  Later  investigations  have  shown,  however,  tliat  nf>  quantitv 
of  urea,  however  large,  introduced  into 
the   circulation   reproduces  the    clinical  ^       ;, 

picture  of  the  uremia.  Blood-plasma 
also  contains  certain  globulicidal  bodies 
destructive  to  red  blood-cells  of  other 
animals.  The  bactericidal  and  antitoxic 
bodies  in  the  blood  have  already  been 
considered.     (See  pjx  98  to  104.) 

Recent  investigations,  both  experi- 
mental and  clinical,  seem  to  indicate 
that  a  study  of  the  freezing-point  of  the 
blood  may  be  of  value  in  certain  cases. 
Normal  blood  freezes  at  about  0.55° 
to  0.58°  C,  below  the  freezing-point  of 
distilled  water.  Agents  causing  renal  ir- 
ritation or  necrosis,  such  as  cantharides, 
and  morbid  conditions  associated  with 
renal  insurticiency,  may  lower  the  freez- 
ing-})oint  to  0.6*^  or  0.8°  C.  or'  even  be- 
yond this  point.  The  removal  of  one 
kidney  similarly  influences  the  freezing- 
point. 

The  chief  solid  constituents  of  the 
blood  are  the  red  corpuscle,  or  erythro- 
cyte: the  white  coqiuscle,  or  leukocvte: 
and  the  l)lood-platelet. 

The  red  l)lood-cell.  or  erythrocyte, 
of    man    is    a    smooth,    highly    elastic, 

biconcave  disc,  which  does  not  possess  a  nucleus.  From  seventy  to 
eighty  per  cent,  of  the  erythrocytes  possess  an  average  diameter  of 
7.5  ".  Of  the  remaining  twenty  per  cent,  about  half  are  slightlv 
larger,  and  the  remaining  cells  slightly  smaller,  than  the  average  given. 
In  the  normal  blood,  cells  smaller  than  usual  are  pro])ably  more  fre- 
quent than  the  larger  cells.  The  smaller  cells  usua  ly  measure  between 
6  ."  and  7  ".  although  cells  measuring  less  than  4  "  (dwarf  cells)  mav 
occasionally  be  observed.  The  larger  cells  are  more  conspicuous  in  in- 
fancy, and  are  rarely  seen  after  adolescence.  In  a  number  of  morbid 
processes  abnomial  form  and  size  constitute  imj)ortant  alterations.  In 
certain  anemias  many  of  the  cells  are  small  (raicrocytes);  the  condition 
is  called  raicrocytosis,  or  microcythemia.     In  some  instances  a  var\-- 


FlG. 


5. — DlAr.RAMUATIC     RePRE-SEXTATIOX 
or    \ARIOtS     FURUS    A.SD    SiZF.S    OF     Rtl) 
CelI-S. — (From      a     cast      oj      prrnuious 
anemia  reportrd  by  Dr.  J .  C.  PaCosIa,  Jr.) 
Erythri)cyu-  (inirtKluccd  (o  itivc  an  apfjroxi- 
matc  idea  of  ihc  size  of  <iihcr  cclJ»).     h.  b. 
-Microtytt.     c.  .MeKaloNa.st.     J.   li    M.i. 
rocyte    (larger    macTix>ncs   are   al-' 
lined,    some   of   which    are    [loiltil  ■     • 
<•.  r.  f.  f.  ,-.  ,-.  ,       l',,ikil...  ^!,>       ,..!,- 
kilocyt'- 
lar    ox. ; 

cyte).     1        .  .     „       c 

extreme  irrcguUnty  ut  (tie  nuJcus  >.••  indi- 
cated. 


4o8  SPECIAL   PATHOLOGY. 

ing  number  of  the  erythrocytes  possess  diameters  of  8  ,"  or  9  //,  or  are 
even  larger;  an  occasional  cell  may  attain  a  maximum  measurement 
of  15  ,".  Such  cells  are  called  macrocytes,  or  megalocytes,  and  the  con- 
dition is  known  as  macrocytosis,  or  macrocythemia.  Microcytes  are 
not  uncommonly  spheric,  and  in  macrocytes  the  biconcavity  is  often 
inconspicuous  or  absent.  Microcytosis  and  macrocytosis  are  frequently 
associated.  The  small  hemal  element  described  by  Eichhorst  is  really 
an  irregularly  staining  microcyte  from  2.5  //  to  4  /^  in  diameter.  It 
differs  from  the  usual  microcyte  in  the  intensity  with  which  it  stains. 

As  a  result  of  disease,  erythrocytes  may  change  their  form,  be- 
coming ovoid,  pyriform,  knobbed,  bobbin-shaped,  etc.  Cells  show- 
ing such  abnormality  in  form  are  called  poikilocytes,  or  schistocytes  ; 
the  condition  is  known  as  poikilocytosis.  Microcytes  and  macrocytes, 
as  wxll  as  the  nucleated  forms  to  be  considered  later,  not  uncommonly 
manifest  more  or  less  irregularity  in  shape,  and  may  be  properly  con- 
sidered as  poikilocytes.  It  is  possible,  by  error  in  technic,  to  produce 
a  distortion  of  the  erythrocytes,  which  may  mislead  the  uninitiated. 
If,  in  making  the  cover-glass  spreads,  as  already  directed,  the  two 
cover-glasses  (p.  385)  be  left  in  contact  too  long,  the  act  of  separation 
may  stretch  the  erythroc^^tes  so  that  one  diameter  will  be  greater  than 


^  P  p  © 

Fig.  226. — Types  OF  Red  Blood-cells;  also  Leuko-  Fig.  227. — Poikilocytes. 

CYTES,  AS  AT  a. — (Landois.) 

another,  a  condition  frequently  observed  in  poikilocytosis.  A  careful 
study  of  such  a  field  will  show  that  the  cellular  distortion  leads  to  an 
elongation  of  all  the  affected  cells  in  one  direction,  a  condition  never 
observed  in  true  poikilocytosis. 

Crenation  is  an  appearance  closely  resembling  poikiloc3'tosis,  but 
develops  after  the  blood  has  been  drawn.  Crenated  cells  are  irregular, 
and  show  knobbed  projections  from  their  surfaces  associated  with  more 
or  less  shrinking  of  the  protoplasm;  by  some  it  is  believed  that  crena- 
tion is  the  extravascular  analogue  of  intravascular  poikilocytosis. 

Early  in  fetal  life  the  nucleated  red  blood-cells  normally  present  at 
that  period  begin  to  disappear,  and  at  birth,  or  shortly  after,  are  no 
longer  present  in  the  normal  blood.  In  certain  morbid  conditions, 
however,  they  form  conspicuous  hemal  elements.  It  is  usually  held 
that  at  some  stage  in  its  evolution  the  red  blood-corpuscle  possesses 
a  nucleus,  which  disappears  before  the  cell  assumes  the  function  of 
a  hemal  cell.  Exactly  how  this  disappearance  of  the  nucleus  is  accom- 
plished has  not  been  accurately  determined.  According  to  some  ob- 
servers, the  nucleus  disappears  by  extrusion,  while  others  think  it  is 
removed  by  a  process  of  absorption  or  of  disintegration.     The  nucleated 


TlIK    m.ool).  40(> 

cells  soon  in  the  blotx,!  are  of  dilTerent  sizes,  justil\'in}^'  U)  a  certain  ex- 
tent   the  division  into  three  kinds. 

Normoblasts  are  nucleated  retl  cells  the  ilianicter  of  which  is  ap- 
proximately that  of  the  normal  erythrocyte.  The  size  of  the  nucleus 
varies,  ami  it  is  usually  eccentric  in  location.  It  is  rich  in  chromatin, 
stains  with  intensity  li\'  tlio  usual  nuclear  stains,  and  not  uncommonly 
contains  a  fine,  intranuclear  net.  Occasionally,  the  nucleus  will  lie  found 
partly  outside  of  the  ])rotoplasm — a  condition  that  suj^'j^^csts  its  extru- 
sion. Sometimes,  in  properly  fixed  pre])arations  evi(lences  of  mito- 
sis may  be  present,  or  the  cell  may  contain  two  or  even  three  nuclei; 
these  may  appear  distinct  and  separate,  while  in  other  cells  connecting 
bands  of  chromatin  may  be  recognized.  The  perinuclear  protoplasm 
contains  more  or  less  hemoglobin,  and  hence  stains  with  the  acid  anilin 
dyes.  The  outline  of  the  cell  is  commonly  uneven,  so  that  a  varving 
percentage  of  these  cells  may  properly  be  called  nucleated  poikilocytes, 
or  poikiloblasts. 

The  microblast  is  a  small  nucleated  form,  smaller  than  the  normal 
red  blood-cell;  both  nucleus  and  protoplasm  are  diminished  in  fjuan- 
tity,  although  occasionally  microcytes  may  be  found  jjossessing  a  nu- 
cleus as  large  as  the  nucleus  of  the  normoblast.  Intranuclear  changes 
are  infrequent.  The  perinuclear  protoplasm  is 
not  uncommonly  shredded,  and  the  cell  is  re- 
garded by  most  observers  as  a  degenerated,  Jjfcf 
necrobiotic,  or  fragmenting  form  of  the  normo-  SK 
blast. 

Megaloblasts,    or    macroblasts    (also    called 
gigautohlasts),    are    abnormally    large   red    cells     j.-,^      ^s.-Crenate..      Rf... 
possessing   nuclei;    the   diameter   of   such    cells  bi/k.d corpuscxes.  —  (/>j«- 

usuallv    exceeds    lo   ",   and    mav    attain    i6   ".      ,^,    ""'      .    .  i    .-    . 

'  -  ...  Often    .seen    in    impropcrlv    lixol 

The   nucleus  is  relatively  large,  but  stams  with  bUwd  slides,  in  freshly -irawn 

less  intensity  than  the  nucleus  of  the  normoblast.  under  \hJ  ^mic'roscoi*?,'"'in 

The  perinuclear  protoplasm  is  usually   rich  in  """^'  '^"^• 

hemoglobin.      The  cell  not  uncommonly  shows 

degenerative  changes,  as  indicated  by  the  unevenness  in  staining 
and  by  the  occurrence  of  vacuoles  in  its  interior.  Frequently  such 
cells  are  irregular  in  conformation,  and  may  be  properly  called 
poikiloblasts.  The  demonstration  that  unusually  large  red  blood-cells 
(megalocytes  or  megaloblasts)  may  contain  more  hemoglobin  than 
corpuscles  normal  in  size  possibly  explains  the  fact  that  in  certain 
diseases  in  which  these  cells  are  comparatively  al)untlant  the  color- 
index  may  be  high.     (See  Pernicious  Anemia.) 

In  addition  to  abnormality  in  size  and  shape,  certain  necrotic  altera- 
tions are  sometimes  })resent  in  the  red  blood-cells.  Hy  some,  poikilo- 
eytosis  is  regarded  as  an  evidence  of  necrotic  change,  and  the  endo- 
globular  alterations  al)Out  to  be  described  are  not  uncommonly  asso- 
ciated with,  or  terminate  in,  the  production  of  poikilocytes.  The  cen- 
tral normally  pale  area  of  the  corpuscle  may  increase  in  pallor,  and 
mav  eventually  lose  all  its  coloring-matter;  the  periphery  at  the  same 
time  mav  show  deepening  of  color.  Sometimes  hyaline  or  vacuolated 
spots  appear  in  the  periphery  of  the  cell,  or  the  cell  becomes  ovoid  in 
profile  with  a  vacuole  at  one  or  both  ends.  A  number  of  these  changes, 
associated  with  solution  of  the  hemoglobin  and  '■tli-'-  <. >inl.i.-  t.-.rtv  r.f 


4IO 


SPECIAL   PATHOLOGY. 


the  cell,  have  been  grouped  by  Arnold  under  the  name  erythrocytolysis, 
or  plasmolysis.  Crenation,  which  ordinarily  is  not  developed  for  some 
time  after  the  blood  is  drawn,  may  be  present  immediately  after  shedding. 
The  knob-like  projections  seen  on  crenated  cells  may  break  off  (plas- 
morrhexis)  and  float  free  in  the  blood. 

Baspohilic  granulation  of  the  erythrocyte  occurs  in  various  types 
of  anemia,  but  approaches  constancy  in  only  one,  that  due  to  chronic 
lead-poisoning.  In  cases  of  this  condition  presenting  an  atypic  symp- 
tom-complex basophilia  becomes  a  prominent  diagnostic  feature.  It 
is  present  in  some  cases  of  pernicious  anemia,  leukemia,  carcinoma, 
malaria,  septicemia,  and  chronic  suppuration.  The  granules  vary  in 
■size  and  may  be  distributed  throughout  the  cell  or  grouped  in  small  or 
large  masses;  they  are  well  shown  by  Wright's  stain.  The  older  view 
that  the  process  is  a  degeneration  of  the  protoplasm  of  the  red  cell  is 
still  held  by  many  observers,  although  Nageli  and  others  consider  it 
regenerative  in  nature.  Vaughan^  has  reached  the  conclusion  that 
basic-staining  granules  in  small  numbers  are  present  in  the  red  cells 
of  healthv  persons,  and  regards  them  as  the  fragmented  remains  of 
nuclei,  this  view  is  in  a  degree  supported  by  the  fact  that  nucleated 
reds  are  usuallv  numerous  in  the  most  marked  cases  of  basophilia. 

The  number  of  red  blood-cells  normally  present  is  approximately 
5,000,000  in  man  and  from  4,000,000  to  4,500,000  in  woman  to  each 
cubic  millimeter  of  blood.  Blood  containing  more  corpuscles  than  nor- 
mal is  said  to  show  polycythemia  (polyglobuly) ;  a  reduction  in  the 
number  of  erythrocytes  is  called  oligocythemia.  Within  the  first  twenty- 
four  hours  following  birth  a  maximum  of  from  6,000,000  to  6,500,000 
may  be  reached.  The  number  is  reduced  by  hemorrhage  and  by  various 
anemias,  which  will  be  considered  later.  The  number  is  reduced  by 
prolonged  exertion,  and  menstruation  usually  induces  a  slight  decrease. 
The  most  marked  diminution  in  number  is  seen  in  pernicious  anemia, 
in  which  the  oligocythemia  may  be  extreme.  Counts  as  low  as  500,000 
are  not  infrecjuent,  and  a  minimum  of  143,000  has  been  recorded. 

Aside  from  the  physiologic  increase  in  the  number  already  noted 
as  present  for  a  brief  period  after  birth,  httle  is  known  of  the  etiologic 
factors  active  in  the  production  of  corpuscular  plethora,  or  polycythemia. 
Impeded  circulation,  or  even  the  influence  of  gravity,  may  slightly 
increase  the  number  of  corpuscles  present  in  a  given  area.  In  cyanosis 
and  in  cardiac  lesions  associated  with  peripheral  stasis  relatively  high 
counts  are  not  infrequent.  The  polycythemia  observed  in  the  cyanosis 
of  congenital  heart  disease  may  be  extraordinary,  as  in  the  case  reported 
by  Baunholtzer — 9,447,000  ervthrocytes,  160  per  cent,  of  hemoglobin. 
As  a  result  of  the  loss  of  fluid"  from  the  vascular  system, — as  by  serous 
diarrhea,  profuse  sweating,  excessive  vomiting,  etc., — the  temporary 
concentration  of  the  blood  increases  the  number  of  corpuscles  present 
in  a  given  quantity.  The  condition  is,  as  a  rule,  temporary  under  such 
circumstances.  An  interesting  form  of  polycythemia  is  that  which 
develops  during  residence  in  high  altitudes.  As  a  rule ,_  the  maximum 
polvcvthemia  resulting  from  this  cause  does  not  manifest  itself  for  a 
month  or  more,  but  not  infrequently  within  twenty-four  hours  after 
the  ascent  a  notable  increase  in  the  number  of  red  blood-cells  may  be 
observed.  Solly  records  an  instance  in  which  a  day's  excursion  was 
'   "Jour,  of  Med.  Research,"   vol.  x,  1903,  p.  342. 


TIIK    lU-OOl).  4  I  I 

attendeil  bv  an  increase  oi  Ooo.ooo  red  cells.  The  total  rise  m  the  num- 
ber of  red  cells  may  reach  from  twenty  to  fifty  per  cent.,  not  infre(juently 
exceeding  the  latter.  The  erythrocruorin  does  not  keep  pace  with  the 
increase  in  red  blood-cells,  although  the  percentage  of  hemoglobin  is  usu- 
allv  augmente<l.  Whether  the  polycythemia  is  due  to  increased  per- 
ipheral distribution,  to  more  active  blood  production,  or  to  the  Icngtheneil 
life  of  the  red  blood-cells  has  not  been  satisfactorily  determined;  the 
last  named  is  possilily  the  most  important  factor.  The  polycythemias 
of  phos[)horus-poisoning,  carbon-monoxid-j)oisoning,  and  that  occasion- 
ally observe<l  in  tuberculosis  have  not  received  any  fully  satisfactory 
explanation. 

Polycythemia  with  chronic  cyanosis  and  enlarged  spleen,'  accompanied 
1)V  vasomotor  and  other  disturbances,  form  a  symptom-complex  of 
which  a  number  of  cases  are  now  on  record.  The  red  cells  usually 
range  between  8,000,000  and  10,000,000,  though  a  count  of  12,000,000 
has  been  found:  the  hemoglobin  commonly  is  from  115  to  160  per  cent, 
with  a  recorded  maximum  of  200  per  cent.  In  some  instances  the  cy- 
anosis is  violet  rather  than  blue,  suggesting  an  added  hyperemia.  The 
disease,  if  it  may  be  called  a  clinical  entity,  is  of  long  duration,  four  to 
ten  or  more  rears.  The  lesion  of  the  spleen  is  commonly  a  diflfuse 
hyperplasia,  though  in  a  few  cases  the  organ  was  little  if  any  enlarged. 
Tuberculosis  was  found  in  one  case,  but  Osier  believes  this  affection 
differs  from  the  somewhat  similar  condition  which  is  found  in  primary 
tuberculosis  of  the  spleen.  The  entire  ])athology  of  this  form  of  poly- 
cythemia is  still  uncertain. 

Structurally,  the  red  blood-cell  appears  to  be  composed  of  two 
elements — a  delicate  reticulum  or  stroma,  but  partly  soluble  in  water, 
inclosing  spaces  within  which  lies  an  albuminous  soluble  portion  of  the 
cell,  which  contains  the  hemoglobin.  This  part  is  freely  soluble  in 
water.  Hemoglobin,  or  erythrocruorin.  is  the  soluble  pigment  to  which 
the  color  of  blood  is  due.  It  is  a  complex  proteid.  readily  decompos- 
able into  a  number  of  so-called  reduction  products.  Some  of  these 
have  been  considered  with  pigments.  (See  Pigmentary  Infiltration, 
p.  233.)  The  amount  of  hemoglobin  present  in  the  blood  varies  within 
certain  limits.  It  may  be  said  that,  approximately,  100  gm.  of  blood 
contain  14  gm.  of  hemoglobin.  It  will  be  recalled  that  in  considering 
the  methods  of  estimating  the  quantity  of  hemoglobin  the  results  are 
commonly  given  in  ])ercentages  of  the  normal.  It  will,  therelore.  be 
apparent  that  when  a  hemoglobinometer  records  100  jjer  cent.,  the 
quantity  indicated  is  14  gm.  in  100  gm.  of  blood.  Hemoglobin  com- 
bines with  oxygen  to  form  oxyhemoglobin,  which,  when  carried  to  the 
tissues,  yields  its  oxygen,  the  hemoglobin  remaining  as  reduced  hemo- 
globin. With  CO  it  forms  a  more  stable  compound,  called  carbon- 
monoxid-hemoglobin.  The  carbon  monoxid  compound  is  not  readily 
dissociated,  and  hence  in  poisoning  by  carbon  monoxid  the  oxygen-carry- 
ing power  of  the  blood  is  held  in  ai)eyance  as  a  result  of  the  inability 
of  the  oxygen  to  displace  the  more  firmly  combined  gas.  Methemo- 
globin.  hematoidin.  hemin.  and  other  pigments  derived  from  the  blood 
have  been  considered  with  pigments  where  they  j)ossess  any  pathologic 
significance,  and  for  further  consideration  the  reader  is  referred  to  text- 
books on  physiology.  As  the  amount  of  hemoglobin  present  in  the  cor- 
'  For  literature,  sec  chapter  on  Diseases  of  the  Spleen. 


412 


SPECIAL  PATHOLOGY 


puscles  largely  influences  their  specific  gravity,  the  latter  has  been 
utilized  as  a  method  of  determining  the  percentage  of  hemoglobin 
present.     (See  p.  397.) 

When  the  quantity  of  hemoglobin  falls  below  the  normal,  the  con- 
dition is  called  oligochromemia.  Hemoglobin  is  diminished  in  all 
anemias,  and  not  uncommonly  its  diminution  is  in  direct  proportion  to 
the  reduction  in  the  number  of  red  blood-cells;  in  other  instances  the 
corpuscular  richness  in  hemoglobin  may  be  greatly  reduced  without 
any  marked  reduction  in  the  number  of  red  blood-cells.  These  altera- 
tions in  the  quantity  of  hemoglobin  present  will  be  considered  with 
more  detail  when  dealing  with  individual  forms  of  anemia. 

Leukocytes. — The  white  cells  of  the  blood,  unlike  the  red,  are  found 
in  a  number  of  forms,  the  relationship  of  one  form  to  another  not  having 

been    clearly    established.     Un- 
^  j^     ^  like    the    red     blood-cells,    the 

leukocytes  are  nucleated,  and 
normally  contain  no  hemoglobin. 
The  proportion  of  leukocytes  to 
red  blood-cells  varies  widely  in 
health,  the  variation  depending 
upon  the  temporary  rise  and 
fall  in  the  number  of  leukocytes, 
irrespective  of  coincident 
changes  in  the  number  of  ery- 
throcytes. All  authors  recognize 
these  fluctuations  in  the  number 
of  leukocytes,  but  all  are  fairly 
agreed  that  the  relative  propor- 
tion of  leukocytes  to  red  blood- 
cells  is  I  of  the  former  to  500  or 
600  of  the  latter.  The  various 
forms  of  leukocytes  exist  in  the 
blood  in  fairly  constant  propor- 
tions. The  different  forms,  the 
general  descriptions,  and  the 
percentages  present  in  the  nor- 
mal blood  will  be  found  in  the 
accompanying  table.  (See  pp. 
414  and  415.)  In  addition, to 
the  groupings  there  given,  several  of  which  possess  only  historic  interest, 
it  is  necessary  to  recognize  that  certain  cells  are  essentially  hemal  and 
that  others  are  essentially  celomic,  although  each  not  uncommonly 
invades  the  domain  of  the  other.  The  normal  number  of  leukocytes  in 
a  cubic  millimeter  of  blood  approximates  from  6000  to  9000. 

In  many  conditions  a  reduction  in  the  number  of  leukocytes  (hypo- 
leukocytosis,  leukopenia,  or  leukocytopenia)  occurs.  Such  reduction 
is  found  with  considerable  constancy  at  some  period  during  the  course 
of  many  of  the  infectious  diseases,  particularly  typhoid  and  paratyphoid 
fevers,  measles,  influenza,  Malta  fever,  leprosy,  malarial  fevers,  and 
uncomplicated  and  advanced  tuberculosis.  Leukopenia  occurs  not 
uncommonly  in  advanced  pernicious  anemia,  splenic  anemia,  secondary 
anemias,    and   in   chronic   enteritis   of   children.     This   phenomenon   is 


Fig.  229. — DiAGR.'^MMATic  Representation  of  Leuko- 
cytes. 

a,  b.  Lymphocytes,  c.  Hyaline  cell.  The  cell  outlines  are 
not  so  sharp  as  indicated,  d,  d,  d,  d,  d.  Finely  granu- 
lar oxyphile  (ix>lymorphonuclear)  leukocytes,  c.  My- 
elocytes. /.  Coarsely  granular  oxyphile  (eosinophile) 
leukocytes. — (From  splcnomediiUary  leukemia;  drawn 
by  Dr.  J .  C.  DaCosIa,  Jr.)  See  Figs.  156  and  157,  p. 
290. 


TIIK    HI.OOI).  413 

not  a  constant  feature  of  any  disease.  The  leukocytes  are  reduced  liy 
starvation,  and  preliminary  to  leukocytosis  —particularly  to  that  form 
called  intlammatory — a"  temporary  leukopenia  is  sometimes  j)resent. 
In  conditions  usually  accompanied  Ly  an  increase  in  the  leukocytes, 
as  appcntlicitis,  peritonitis,  and  pneumonia,  an  overwhelming  infection 
ma\-  not  onlv  prevent  an  increase  but  actually  cause  a  decrease  in  those 
cells.  Under  such  circumstances,  leukopenia  possesses  the  gravest 
prognostic  significance.  In  marked  cases  of  hypoleukocytosis  the  num- 
ber of  leukocvtes  may  be  600  or  even  less  to  the  cubic  millimeter  of  blood. 
The  essential  cause  of  this  condition  is  not  known.  It  is  held  by  some 
that  there  is  a  faultv  jiroduction  of  leukocytes;  by  others,  that  there 
is  an  increased  destruction — leukolysis.  It  is  not  improbable  that  both 
factors  are  operative.  Faulty  distribution  may  have  something  to  do 
with  diminution  of  leukocytes  in  the  ])erii)heral  circulation,  as  indicated 
by  its  occurrence  after  prolonged  cold  baths  and  reduction  of  blood 
pressure,  the  normal  distribution  being  altered  as  a  result  of  leukocytic 
accumulation  in  the  large  viscera,  particularly  the  lungs. 

In  addition  to  the  reduction  in  number,  leukocytes  not  uncommonly 
show  evidence  of  extensive  karyolysis.  One  of  the  most  marked  karyo- 
lytic  changes  is  that  observed  in  the  polymorphonuclear  cell  in  pyogenic 
processes.  The  pus-cell,  with  its  many  irregularities  in  protoplasm  and 
nucleus,  is  a  polvmorphonuclear  cell  showing  the  results  of  karyolytic 
change  brought  about  by  the  activity  of  the  bacterial  toxins,  in  pro- 
nounced anemia,  or  in  other  conditions  associated  with  blood  destruc- 
tion, the  leukocytes  may  contain  fragments  of  red  blood-cells  and  parti- 
cles of  pigment  derived  from  various  sources;  such  cells  are  called 
inclanifcrous  leukocytes.  By  some  they  are  accorded  great  value  in  the 
diagnosis  of  malaria.  Abnormality  in  color,  reaction,  position,  size, 
and  distribution  of  leukocytic  granules  is  not  uncommonly  present; 
such  variations  are  probably  evidences  of  degenerative  change. 

Leukocytosis. — As  already  indicated,  a  wide  variation  in  the  number 
of  leukocvtes  is  compatible  with  health.  Efforts  to  draw  absolutely 
exact  limits,  beyond  which  the  normal  fluctuations  do  not  go.  have  been, 
for  the  most  part,  illusive.  If  a  comparatively  low  standard,  such  as 
8000  or  9000,  or  even  10,000,  to  the  cubic  millimeter  be  adopted,  it 
will  be  found  that  not  uncommonly  the  number  of  leukocytes  exceeds 
this  arbitrary  boundary  without  there  being,  of  necessity,  any  evidence 
of  disease.  On  the  other  hand,  if  a  standard  above  this  point,  or  at 
least  verv  much  higher,  be  chosen,  it  will  be  observed  that  in  certain 
well-recognized  morbid  conditions  the  associated  leukocytosis  falls 
within  the  limit  decided  upon.  It  will  thus  be  seen  that  it  is  quite 
impossible  to  draw  a  fixed  line  and  to  say  that  beyontl  this  the  accumu- 
lation of  leukocvtes  is  abnormal,  while  under  this  quantity  the  number 
is  essentially  normal.  A  standard  of  10,000  to  the  cubic  millimeter 
has  been  generally  accepted  as  the  maximum  normal  leukocytic  count. 
There  can  be  no  objection  to  the  figure,  provided  it  is  understood 
that  this  number  is  arbitrary  and  open  to  the  objections  just  pointed 
out.  Leukocvtosis  is  either  absolute  or  relative,  or  both.  The  former 
means  an  absolute  increase  in  the  number  of  leukocytes  in  the  peripheral 
blood;  the  latter  signifies  an  increase  of  one  variety  at  the  expense  of 
the  others. 

In  a  general  way  it  may  be  said  that  leukocytosis  is  physiologic  or 


VARIETIES  OF 


Wharton          Max 
Tones.       Schultze. 
'1846.      ,       1865. 

Metchni- 

KOFF. 

Ehrlich. 

Kanthack 

and 

Hardy. 

Hayem. 

Percentage  Present 

IN  Normal 

Blood. 

Non- 
granular 

Small 
round 
cell  I. 

Lympho- 
cyte. 

Lympho- 
cyte. 

r 

Small 
Large 

Lympho- 
cyte. 

Leuko- 
cytes of 
the  first  ' 
variety. 

Small 
type- 
Large 
type. 

15  to  30. 

nucleated 
cells.    . 

Large 
round 
ceUII. 

Macro- 
phagocyte. 

HyaUne. 

cell. 

2  to  6. 

Granule 
cells  finely 
granular. 

Cells  wn'th 
finely 
granular 
proto- 
plasm. 

Micro- 
phagocyte 

Cells   neutrophile 
in  man,  ampho- 
phile  in  some  of 
the     lower   ani- 
mals. 

[Note. — Through- 
out the   ^■olume 
I  have  referred 
to  these  cells  as 
polymorphonu- 
clear leukocytes.j 

Finely 
granular 
oxvphile 
cells. 

Leukocytes  of  the 
second  variety. 

60  to  72 

Granule 
cells 
coarsely 
granular. 

CeUs  with 
coarsely 
granular 
proto- 
plasm. 

Eosino- 
philes. 

Leucocytes  with 
a  granules. 

Coarsely 
granular 
oxyphile 
or  acido- 
phile  cells. 

Leukocytes  of  the 
third  variety. 

Rarely  over  two  per 
cent.;  in  childhood 
may  reach  11  to  14 
per  cent. 

Cells  containing 
y  granules. 
"Mastzellen." 

Coarsely 
granular 
basophile 
cells. 

Rarely  if  ever  present  in 
normal  blood, present 
in  celomic  fluids  and 
connective  tissues. 

Cells  with 

Granule        ,     finely 
cells  finely      granular 
granular.        proto- 
plasm. 

Basophile  cells 
with  &  granules. 

Finely 
granular 
basophile 
cells. 

Rarely  exceeds  .25. 

Myelocytes. 
Marrow  cells. 
("Markzellen" 
of  German 

writers.) 

Hypertrophied 
white  cells. 

Not  present:  found  in 
bone  -  marrow  (red) 
and  present  in  blood 
in  leukemia. 

'  After  Adami's  table  (Allb^^tt's    "Sj^s.  Med.," 


414 


LtLiKOCYTHS.' 


Size. 


FuRiHtK  Description 


I  I  to  15  M-. 


tr.  ..  u  iisiuillv  il,«ui  Dffplv  stiiininR,  rilativrly  hirni-  nurk-us  occupyinK  most  oi  the  cill.  laini  riiiK  <•(  n..n- 
,h,!  ..'t;.  nf  mrmi  Rranular  ,.rot.^,lasm.  Contains,  rarely.  l.as..|.l.ilic  RranuUs.  H..lh  amrl-.i.l  ami 
r»H  MrU  r.:il  "Vu  phaRocylic.  The  larRcr  ..f  thist-  ciUs  can  not  Ih.-  .lifftronlialcd  from  the  hyaline  tell, 
rea  uiooa-ciu,  ,.5  »»•       l.„i,uIalion  or  polymorphism  of  the  nucleus  rarely  present. ^^ 

Faintly  staining,  relatively  large,  round,  oval,  notched  or  reniform  nurleu<i,  slightly  Inrsrr 
thaii  al>ove.     Hroader  ring  of  hvalinc.  faintly  pinkish,  grayish  or  light  Mue.  non  granular 
protolJasm.     .\ctivcly  amelM>iii  and     phagocytic.      .Nucleus  sometimes    surroundeil  liy 
taint  rim  of  hyaline  protoplasm,  outside  of  which  Iwsophilic  granules  may  be  present. 
!     (This  reaction  best  brought  out  by  eosin  and  methyleneblue.) 

This  cell  is  .-Uso  known  as  the  polymorphonuclear  leukocyte  or  polymorphonuclear  ncu- 
trophile.  It  is  sometimes  called  the  iKilynurlear  leukocyte.  Irregularly  staining  nucleus; 
the  nucleus  is  irregular,  lobulated,  reniform  and  not  uncommonly  like  the  ligure  .?,  5  or  7, 
or  it  may  resemble  the  letter  s,  z  or  u.  The  nucleus  may  be  apparently  divi.icd  into  three, 
live  or  even  six  p;irts.  commonly  connected  by  "underground"  bands  of  chromatin;  in- 
ability to  demonstrate  connectiim  between  the  different  parts  of  the  nucleus  led  to  the 
sup|K')sition  that  the  cell  was  multinucleated  or  |X)lynucleated.  Irregularity  in  the  con- 
tour of  the  nucleus  is  probably  due  to  its  being  dried  and  ti.xed  while  still  manifesting 
ameboid  activitv.  The  nuileus  is  rich  in  chromatin  bands  which  may  form  a  recogniz- 
able network  iii  its  interior.  Protoplasm  finely  granular.  The  granules  formerly  la-- 
lieved  to  be  neutrophile  are  now  regarded  as  faintly  oxyphile  or  acitlophile.  The  gran- 
ules are  commonly  demonstralJc  over  as  well  as  around  the  nucleus.  The  cell  is  ac- 
tively ameboid  and  phagocytic.  Mitotic  and  amitotic  division  of  the  cells  is  .sometimes 
demonstrable.  These  cells'  are  sometimes  regarded  as  the  adult  leukocytes  of  the  MimkI. 
They  are  the  most  important  if  not  the  only  pus  cell.  Sometimes  cells  are  seen  in  the 
blood  partaking  of  the  characteristics  of  both  the  mononuclear  and  faintly  o.xyphile 
tyix-s;  such  cells  are  sometimes  spoken  of  as  transitional  leukocytes.  I  he  writer  is 
not  kindly  inclined  toward  the  use  of  the  word  "transitional."  Its  use  is  cxcu.sed 
only  by  the  fact  that  in  enumerating  leukocytes  occasionally  cells  are  encountered  which 
can  not  be  definitely  i)laced.  Reference  has  lieen  made  to  this  when  consi<lering  the 
lymphocytes  and  hyaline  cells,  between  which   we  Ulieve  we  recognize    interme<liatc 

1      forms.     SutTicient  care  in  staining  and  careful  focusing  will  usually,  although  not  always, 

I      cnalile  one  to  differentiate  Ix-tween  these  tyjx-s. 


Usually  smaller  than 
the  preceding  type. 
Diameter  ranges  l>c- 
tweett  7  and  10  n. 


Nucleus  pos.ses.sing  manv  of  the  characters  of  the  preceding  variety.  Rarely  centrally 
placc-d.  Chromatin  network  less  conspicuous,  often  not  recogniz;ible;  cells  iiot  un- 
commonly dearly  polvnuclear  without  recognizable  connecting  or  "underground"  chro- 
matin bands  bet'ween'the  different  nuclei.  Horseshoe  shaped  anil  reniform  nuclei  Irc- 
quent.  Cell  protoplasm  not  easily  identified,  with  the  exception  of  the  gninules.  whii  h  arc 
conspicuous  even  in  the  unstained  cells.  Granules  large,  deariy  defined,  highly  re- 
fractile.  usually  discrete,  but  may  l>e  s<i  abundant  that  .lifferenliation  is  iiot  e;i>y;  thi-v 
take  acid  stains  intensely.  Slain  reddish  brown  with  Khriich's  stain.  .Actively  amelxjid, 
not  u.sually  believed  to  be  phagocytic.  Granules  or  matrix  may  contain  bactericidal  sub- 
stances. 


Faintly  staining,  round  or  oval,  structureless  nucleus.     Protopla.sm  usually  diflTicult  to 

Relatively  large;   may  l      dcmon.stratc.  may  appear  irrcgulariy  notched  al  the  margin,  granules  slightly  rcfractilc 

exceed  20  n.  in    un.stained    .specimens,    large    and    abundant;    stain    deeply  (purpUsh    blue)  with 

methyleneblue  or  with  the  dahlia  formula.  


Rarely  attains  size  of  1  Finely  granular  and  coarsely  granular  cells  are  de.scnIxHl  by  soiric  wnters  .is    masta-llen. 

the   finely  granular  i      Nucleus  round  or  irregularly  indentiii.      Stains  faintly,  usuaUy  with  less  intensity  than 
oxyphile  cell  usually         the  granules,  but  of  the  same  color.    Granules  like  preceding  variety,  but  *-er>  I'"'- 
much  smaller. 


Usually  II  to  18  m:  a\ 
erage  alx>ut  15  f. 


Pale,  uniforn-lv  staining,  eccentrically    placed,  ovoidal  < 
hvidine  cell.     Protoplasm  varies  in  ((uantity.     The  gr. 
are  usually  not  to  U-  differentiati'<l  from  the  granulo  "f 
Stain  reaction  of  the  granules  is  liot  constant.      I- ■ 
gr.idaliims  of  stain  reaction  iKcasionally  pres«-nt 
to  demonstrate  the  presence  of  granules,      liv   I 
figures  ni.iv  Ih-  present.      Probably  i'lentical  ^' 
mn^idcr^  them  intermediate  between  the  1; 
cell.     W  bile  found  in  other  diseases,  it  is  in  ■ 
myelocytes  assumes  great  diagnostic  importance. 


ir  rou 
nub" 

ill.   1 


nd  nucleus 
present  in 


,  resi-ml  ling 
the    protopl; 

.,r..x\|.lulr    . 


the 


I.til 


vol.  i,  p.  79);    modified  and  extended. 


415 


4l6  SPECIAL  PATHOLOGY. 

pathologic.  The  leukocytosis  occurring  during  digestion,  the  leukocytosis 
of  the  new-born,  which  not  uncommonly  persists  until  the  end  of  the 
first  year,  and  the  leukocytosis  at  times  associated  with  pregnancy  are 
taken  as  examples  of  the  so-called  physiologic  leukocytosis.  Digestive 
leukocytosis  is  sometimes  quite  marked,  but  ordinarily  the  increase  is 
not  more  than  33  per  cent.  The  cellular  elements  in  excess  are  the 
lymphocytes  and  polymorphonuclear  cells;  sometimes  the  increase  is 
more  marked  in  one  than  in  the  other.  This  point  is  of  value,  as  a  blood 
examination  made  during  digestion  might,  as  a  result  of  the  large  Ivmpho- 
cytic  count,  lead  to  erroneous  conclusions,  and  the  finding  of  an  excess 
of  polymorphonuclear  cells  might  also  mislead.  When  gastric  digestion 
is  deficient  or  greatly  delayed,  it  occasionally  happens  that  there  is  no 
digestive  leukocytosis,  and,  hence,  the  absence  of  digestive  leukocytosis 
is  not  uncommonly  regarded  as  an  evidence  of  gastric  disorder.  Some 
observers  regard  this  leukocytosis,  which  is  most  constant  after  the 
midday  meal,  as  largely  a  diurnal  variation,  its  occurrence  having 
been  noted  in  fasting  persons.     Cabot  ascribes  to  it  no  diagnostic  value. 

Inflammatory  Leukocytosis. — This  form  is  most  frequently  associated 
with  suppurative,  septic,  or  other  inflammatory  processes,  and  is  not 
uncommonly  preceded  by  a  brief  stage  of  leukopenia,  the  extent  and 
duration  of  which  depend  upon  the  promptness  with  which  the  body 
tissues  react,  and  also  on  the  virulence  of  the  infecting  factor.  The 
prompt  occurrence  of  this  form  of  leukocytosis  in  acute  infective  dis- 
orders— such  as  pneumonia,  acute  bacterial  conditions  affecting  serous 
membranes,  streptococcal  and  staphylococcal  infections,  scarlet  fever, 
and  allied  conditions — is  regarded  as  a  favorable  omen;  the  occurrence 
of  a  leukopenia  that  persists  is  held  to  be  an  evidence  of  weak  resistance 
or  of  overwhelming  infection.  Not  uncommonly  the  count  in  inflamma- 
tory leukocytosis  approaches  35,000,  40,000,  or  50,000,  and  in  rare 
instances  the  number  of  leukocytes  present  may  be  considerably  greater. 
The  leukocyte  most  abundant  in  this  condition  is  the  polymorphonuclear 
cell.  The  large  numbers  of  these  cells  present  in  the  blood  may  so 
alter  the  percentage  that  repeated  accurate  observations  show  that 
from  ninety  to  ninety-five  per  cent,  of  the  leukocytes  are  of  this  type. 
In  some  cases  there  is  an  increase  in  the  number  of  lymphocytes.  As 
in  other  forms  of  leukocytosis,  various  opinions  have  been  held  as  to 
the  source  of  the  added  leukocytes  and  the  essential  etiology  of  the 
condition.  It  has  been  held  that  the  leukocytosis  is  the  result  of  nothing 
more  or  less  than  altered  distribution;  the  polymorphonuclear  cells 
leaving  the  celomic  cavities  and  entering  the  blood  in  response  to  in- 
fection. While  it  is  not  improbable  that  such  a  cause  may  be  active, 
the  large  number  of  leukocytes  destroyed  at  the  point  of  infection, — 
as,  for  example,  in  abscess  formation,^ — and  the  evidence  of  increased 
leukolysis,  as  shown  by  the  excretions,  point  to  the  occurrence  of  in- 
creased leukocytic  production. 

The  leukocytosis  of  malignant  disease,  s^^philis,  rickets,  and  the 
leukocytosis  following  hemorrhage,  as  well  as  that  which  not  un- 
commonly precedes  death  (agonal  leukocytosis),  are  by  some  writers 
grouped  with  the  inflammatory  increase  of  leukocytes.  The  leuko- 
cytosis observed  in  connection  with  malignant  disease  usually  consists 
of  an  increase  in  the  mononucleated  forms  of  leukocytes;    the   same 

' See  p.  295. 


Tin-:  iu,(.)(»i). 


4'7 


is  true  of  rifkets.  syphilis,  and  a^'onal  leukocytosis,  wlule  that  follow- 
ing hemorrha^'c  is  usually  of  the  polymorphonuclear  tvpe.  Leuko- 
cytosis is  usually  more  marked  in  the  presence  of  sarcoma  than  in 
carcinoma,  and  is  particularly  evident  when  the  former  disease  attacks 
the  lymphatic  structures.  The  increase  in  leukocytes  met  with  in  cases 
of  gout,  nephritis,  quinin  j)oisoninii:  and  similar  conditions,  and  after 
etherization  is  sometimes  called  toxic  leukocytosis. 

Artificially  induced  leukocytosis,  or  leukotaxis,  has  been  suggested 
as  a  means  of  increasing  local  or  general  resistance  to  infection  ;  although 
as  yet  in  the  trial  stage,  the  expedient  appears  promising. •  I'ctit  aug- 
mented the  resistance  of  the  peritoneum  of  animals  by  injecting  heated 
horse  serum,  and  also  obtained  satisfactory  results  with  human  beings; 
Mikulicz  employed  subcutaneous  injections  of  nucleinic  acid  before 
operation.  The  efficacy  of  these  measures  lies  in  the  increa.se  of  poly- 
morphonuclear leukocytes,  which  is  said  to  be  from  g  to  425  per  cent. 

Eosinophilia  is  a  debatable  term  used  to  signify  an  increase  of  the 
eosinophile  leukocytes  of  the  blood.  The  condition  is  very  constantly 
observed  in  many  diseases  of  the  skin,  some  bone  affections,  bronchial 
asthma,  and  myelogenous  leukemia.  The  greatest  diagnostic  value  of 
this  form  of  leukocytosis  is  in  connection  with  the  presence  of  intestinal 
or  other  parasites,  as  in  cases  of  uncinariasis,  trichiniasis,  hydatid  disease 
and  filariasis.  Counts  of  eosinophiles  as  high  as  sixty  per  cent.,  or  even 
more,  of  the  total  number  of  leukocytes  have  been  recorded. 

Blood-platelets  are  spheric,  ovoid,  or  irregular  non-nucleated  bodies, 
from  I  !i  to  4  //  in  diameter,  found  free  in  the  blood-plasma.  Their 
number  ranges  from  180,000  to  400,000  per  cubic  millimeter.  They  disap- 
pear rapidly  from  blood  exposed  to  the  air.  and  special  technic  is  neces- 
sary' to  observe  them  in  the  fresh  specimen.  But  little  is  known  of  their 
origin  or  significance.  The  general  oi)inion  is  that  thev  are  formed  in 
the  red  cells,  from  nuclei  or  other  cast-of?  material.  '  Thev  possibly 
originate  from  the  nuclei  of  leukocytes.  They  are  numerous  in  white 
thrombi  and  appear  primarily  active  in  the  formation  of  other  types 
of  thrombus.  By  some  they  are  regarded  as  the  source  of  one  of 
the  elements  of  fibrin  ferment.  The  platelets  are  increased  in  most  of 
the  anemias,  particularly  chlorosis,  leukemia,  pneumonia,  tuberculosis, 
myelitis,  and  numerous  other  conditions.  They  are  diminished  in  pur- 
pura, hemophilia,  and  many  acute  fevers.  The  platelets  are  well  shown 
by  Wright's  stain,  but  are  not  demonstrable  bv  Ehrhch's  mixture. 

Hemocytolysis  or  Hemolysis. — Dissolution  of  the  red  blood-cell  with 
liberation  of  the  hemoglobin  and  endoglobular  changes  in  the  cell  cvto- 
plasm  not  infrequently  occur  in  a  sufficiently  marked  form  to  deserve 
consideration  as  a  distinct  pathologic  process.  BUjod  destruction  is. 
in  a  sense,  normal.  The  liberated  blood  coloring-matter  resulting  from 
cell  dissolution  is  converted,  in  the  liver,  into  bile  pigment,  and  possiblv 
enters  into  other  normal  chemic  processes.  When  the  process  exceeds 
the  normal  or  when  cell  destruction  assumes  an  abnormal  tvpe.  the 
resulting  condition  is  spoken  of  as  hemocytolysis,  hemoglobinemia,  or 
by  some  writers  as  hemolysis.  In  the  (ondition  nndcr  consideration 
the  cell  elements  primarily  involved  are  the  erythrocytes:  when  the 
cell  destruction  involves  l)oth  red  cells  and  leukocytes  (er\-thr'>.  .  t-.tv^w 
and  leukolysis).  the  term  hemolysis  is  more  appropriate. 

'See  summan,-  of  literature  by  Rnmmc.    •  La  PnsscMeflicalc."  Ian    i>.  i<jo; 
28 


4l8  SPECIAL   PATHOLOGY. 

Of  the  many  causes  presumed  to  be  active  in  the  production  of 
hemocvtolysis,  no  one  satisfactorily  explains  the  occurrence  of  the  mani- 
festation under  all  circumstances.  When  foreign  blood  is  introduced 
into  the  circulation  of  an  animal,  and  particularly  when  such  blood  is 
from  an  animal  of  another  species,  the  added  hemal  cells  promptly 
undergo  fragmentation.  The  introduction  into  the  circulation  of  large 
quantities  of  fluid  may  give  rise  to  destruction  of  normal  erythrocytes. 
Hemocytolysis  occurs  in  connection  with  certain  infectious  diseases, 
among  which  may  be  mentioned  smallpox,  scarlet  fever,  diphtheria, 
enteric  fever,  and,  possibly,  to  a  varying  extent,  all  the  acute  exanthe- 
mata. Bacteria  and  bacterial  products  circulating  in  the  blood,  as  in 
septicemia  and  pyemia,  may  bring  about  the  change,  and  a  number  of 
microorganisms  have  been  shown  to  produce  hemolytic  poisons  through 
the  activity  of  which  blood-destruction  is  accomplished.  Malaria  always 
induces  more  or  less  erythrocytolysis,  and  in  certain  forms  the  process 
assumes  grave  proportions.  Many  poisons  induce  a  similar  change,  and 
hemolysis  arising  from  such  causes  is  called  toxic.  A  long  list  of  poisons 
possessing  the  power  might  be  given,  the  most  important  of  which  would 
be  chlorate  of  potash,  arseniureted  and  phosphoreted  hydrogen,  carbolic 
acid,  pyrogallic  acid,  and  various  coal-tar  derivatives  other  than  those 
mentioned,  such  as  anilin,  antifebrin,  antipyrin,  etc.  The  blood  de- 
struction associated  with  poisoning  by  various  fungi,  and,  indeed,  the 
destruction  accompanying  the  introduction  of  venom,  might  properly 
be  grouped  with  this  class.  Extremes  of  temperature  seem  to  be  influ- 
ential in  the  production  of  this  condition,  and  local  tissue  destruction 
from  burns  or  frost-bites  may  bring  about  the  change.  The  condition 
is  sometimes  associated  with  Raynaud's  disease.  A  form  of  hemocyto- 
lysis is  clinically  recognized  as  paroxysmal  hemoglobinuria. 

Whatever  may  be  the  cause  of  the  cell  dissolution,  liberated  hemo- 
globin may  be  excreted  by  the  kidney  (hemoglobinuria)  as  methemo- 
globin  or  oxyhemoglobin,  or  the  latter  may  be  converted  into  the  former 
by  more  or  less  prolonged  retention  within  the  bladder,  and  a  sufficiently 
long  stay  in  this  organ  may  lead  to  the  final  conversion  of  oxyhemo- 
globin into  acid  hematin.  An  examination  of  the  blood  usually  shows 
that  it  is  dark  in  color,  and  the  serum  secured  by  coagulation  or  by 
the  centrifuge  may  possess  a  hemoglobin  tint.  Blister  serum  obtained 
from  the  patient  may  show  the  spectroscopic  lines  of  free  hemoglobin. 
There  is  usually  a  marked  reduction  in  the  number  of  erythrocytes, 
associated  with  the  presence  of  degenerating,  fragmenting  cells,  chloro- 
cytes,  and  achromocytes.  Poikilocytosis,  microcytosis,  and  megalocy- 
tosis  are  present  to  varying  degrees.  The  reduction  in  hemoglobin 
may  be  marked.  As  a  rule,  there  is  little  change  in  the  number  of  leu- 
kocytes, although  evidence  of  leukolysis  may  be  present.  The  liver 
mav  be  unequal  to  the  task  of  removing  the  large  quantity  of  hemo- 
globin, even  with  the  occurrence  of  polycholia.  The  liver  cells  may 
manifest  granular  change  and  bile-staining;  free  pigment  is  not  uncom- 
monlv  present  in  the  hepatic  tissues.  No  constant  renal  lesion  is  de- 
monstrable, although  the  kidney  shows,  for  the  most  part,  considerable 
staining,  and  the  secreting  substance  may  be  brown  or  brownish-red 
in  color;  granular,  desquamative,  and  other  degenerative  changes  may 
l)e  seen  in  the  renal  epithelium  in  marked  cases,  and  free  pigment  may 
be  present  in  the  tubules;    the  Malpighian  tufts  are  said  to  escape  the 


TllK    BLOOI).  419 

deposit.  Mention  has  already  been  made  of  the  hemoglohinuna.  llcino- 
j,'l()l)in  infarcts  occur  in  the  kidneys,  and  infarction  is  occasionally  j)resent 
in  other  orphans. 

Regeneration  of  the  Blood. — After  extensive  hemorrhage,  and  from 
other  causes,  direct  loss  and  blood  destruction  may  reduce  the  number 
of  red  cells  to  i. 000.000  or  less.  Usually,  with  the  subsidence  of  the 
cause  regenerative  processes  rapidly  ensue.  After  the  loss  of  Llood  a 
temporary  hydremia  is  brought  about  by  the  abstraction  of  fluid  from 
the  tissues,  thereby  restoring  the  volume  of  the  circulating  medium  by 
increasing  the  liquid  portion.  The  leukocytes  are  rapidly  replaced, 
jjrobablv  from  the  tissue  spaces,  and  often  become  moderately  increased 
in  number,  a  distinct  polymorphonuclear  leukocytosis  occurring.  Later, 
the  mean  diameter  of  the  erythrocytes  falls,  and  normoblasts  are  present 
in  varying  quantities.  The  fall  in  hemoglobin  is  at  first  proportional 
to  the  reduction  in  the  number  of  red  blood-cells,  but  later  the  color- 
index  drops,  and  may  fall  as  low  as  0.5.  During  the  process  of  erythro- 
cvtic  regeneration  nucleated  cells  may  appear  in  varying  numbers. 
The  ervthrocvtes  increase  more  rapidly  than  the  hemoglobin,  and, 
hence,  for  a  time  the  color-index  remains  low. 

The  length  of  time  necessary  for  complete  regeneration  of  the  blood 
varies  with  the  recuperative  and  hematogenic  power  of  the  individual 
and  with  the  extent  of  the  hemorrhage.  Repeated  hemorrhage  weakens 
the  regenerative  powers  more  rapidly  and  to  a  greater  extent  than  a 
single  copious  hemorrhage.  Attempts  to  establish  a  definite  period 
within  which  hemal  regeneration  will  occur  are  not  well  founded,  by 
reason  of  the  uncertainty  in  hematopoiesis  in  different  individuals. 

Anemia. — The  term  anemia  has  been  variously  defined,  but,  so  far 
as  a  definition  goes,  nothing  better  has  been  off'ered  than  to  call  it  "  a 
povertv  of  the  blood."  In  certain  classes  of  cases  the  anemia  is  appar- 
entlv  dependent  upon  defects  of  the  blood-making  or  blood-destroying 
organs,  or,  possibly,  it  would  be  better  to  say  faults  of  hematogenesis 
or  hemolvsis,  or  both.  Anemias  in  which  no  sufficient  cause  can  l>e 
recognized  in  the  organs  or  tissues  are  commonly  referred  to  as  primary 
anemias.  In  another  class  of  anemias  the  blood  condition  is  dependent 
upon  some  more  or  less  evident  lesion.  These  are  the  so-called  sec- 
ondary anemias.  As  our  knowledge  of  pathology  progresses  we  will. 
no  doubt,  class  as  secondary  some  of  the  anemias  now  regarded  as 
primarv.  When  we  have  demonstrated  the  factors  influential  in  the 
production  of  an  anemia,  it  becomes  secondary  to  its  demonstrated 
cause. 

Secondary  Anemia. — It  is  prf)posed  to  consider  with  this  class  those 
anemias  in  which  it  is  possible  to  demonstrate  a  cause  believed  to  be  a 
sufficient  explanation  of  the  recognized  change.  As  blood  production 
is  dependent  largely  upon  the  general  nutrition  and  health  of  the  indi- 
vidual, as  well  as  upon  the  hematogenic  functions,  properly  so  called, 
it  becomes  evident  that  a  large  number  of  etiologic  factors,  often  not 
even  remotelv  associated,  can  be  classed  with  the  causes  of  symptomatic 
anemia.  Unsanitary  surroundings;  improper,  pocrr,  or  scanty  food; 
overwork  with  insufficient  food;  emotional  conditions  influencing  the 
appetite,  sleep,  etc..  may  all  possess  a  var>-ing  importance  in  the  pro- 
duction of  anemia.  Hemorrhage,  copious  and  single,  or  scanty  and 
repeated,  may  also  be  a  cause.     Painful  affections,  by  reason  of  their 


420  SPECIAL  PATHOLOGY. 

influence  upon  the  primary  and  secondary  assimilation,  may  also  favor 
the  occurrence  of  an  anemia.  Intestinal  parasites — such  as  the  Uncin- 
aria  duodenale^  and  Dibothriocephalus  latus^ — may  induce  anemia 
by  interfering  with  the  digestive  process,  by  inducing  hemorrhage,  and 
possibly  bv  elaborating  some  absorbable  poison  that  influences  un- 
favorably blood  production  or  induces  destruction.  Anemia  may  depend 
upon  the  presence  of  parasites  within  the  blood;  the  most  conspicuous 
of  these  is  the  organism  of  malaria. 

Acute  infectious  diseases  commonly  impoverish  the  blood.  During 
the  activity  of  such  processes  the  anemia  may  not  be  conspicuous,  but 
with  convalescence  it  not  uncommonly  becomes  evident.  With  this 
group  should  be  classed  anemias  following  typhoid  fever,  scarlet  fever, 
smallpox,  etc.  So-called  chronic  infectious  diseases  are  also  associated 
with  the  occurrence  of  anemia,  which  may  of  itself  be  a  striking  symp- 
tom; the  anemias  of  syphilis  and  tuberculosis  are  most  typical.  The 
anemia  of  scurvy  and  purpura  should  be  mentioned.  Certain  of  the 
secondary  anemias  are  called  toxic,  and  are  dependent  upon  poisoning 
by  lead,  arsenic,  phosphorus,  mercury,  etc.  Mahgnant  tumors  (car- 
cinoma and  sarcoma)  usually  give  rise  to  a  form  of  anemia  that  may 
constitute  an  important  factor  in  the  diagnosis  of  such  conditions. 

Diseases  of  various  organs  influencing  the  general  nutrition  are  not 
uncommonly  associated  with  anemia.  The  anemias  of  chronic  neph- 
ritis, of  heart  disease,  and  of  chronic  intestinal  inflammations  belong 
to  this  group. 

The  Conditions  in  Secondary  Anemia. — The  table  on  pages  428  and 
429  gives  in  a  general  way  the  blood  changes  in  this  condition.  It  is 
probable  that  the  disease  ordinarily  referred  to  as  simple  anemia  is 
truly  an  example  of  secondary  anemia,  and  that  it  should  be  considered 
with  this  group.  It  will  be  observed  that  the  blood  changes  in  secondary 
anemia  possess  nothing  characteristic,  and  depend  more  upon  the  in- 
tensity of  the  anemia  than  upon  any  other  factor.  The  reduction  in 
red  blood-cells  varies  within  wide  limits.  A  fairly  evident  secondary 
anemia  mav  show  a  blood  count  of  4,500,000,  while,  at  the  other  ex- 
treme, a  count  below  1,000,000  may  occur.  The  corpuscular  changes 
also  depend  upon  the  extent  of  the  anemia.  It  may  be  said  that  in  the 
milder  anemias  there  is  little  distortion  of  the  erythrocytes,  and  but 
few  abnormal  cells  are  present.  In  more  marked  secondary  anemias 
poikilocytosis  and  microcythemia  occur,  while  in  the  graver  forms 
megalocytes  and  nucleated  erythrocytes  are  found;  megaloblasts  are 
rare;  normoblasts  are  more  abundant.  Polychromatophilia  (abnormal 
stain  reaction)  is  usually  proportionate  to  the  degree  of  the  anemia. 

The  hemoglobin  always  shows  greater  reduction  than  the  erythro- 
cytes (low  color-index),  and  may  not  exceed  twenty  per  cent.  The 
leukocytes  are  but  little,  if  at  all,  influenced  by  the  mere  occurrence 
of  secondary  anemia.  The  condition  that  produced  the  anemia  may 
determine  a  leukocytosis  the  character  of  which  will  depend  upon  the 
cause.  It  is  usually  stated  that  when  the  blood  counts  are  low,  a  leuko- 
cytosis is  likely  to  be  present;   this  is  not,  however,  an  invariable  rule. 

The  visceral  lesions  associated  with  this  form  are  dependent  upon 
the   cause   and   upon   the   extent   of  malnutrition.     Granular   changes 
occur  in  glandular  viscera,  notably   the  kidney  and  liver.     A  similar 
*  See  p.  205.  ^  See  p.  201. 


TIIK    HI.UOD.  421 

cliangL"  IS  sfcn  111  tlic  hcari;  sometimes  the  iii\ oranhum  will  l»r  lound 
distinctly  fatty.  Deijenerative  changes  in  the  capillary  system  are 
indicated  by  the  concomitant  edema.  The  degenerative  lesions  are 
j)rol)ahly  dependent  upon  overwork  of  the  organs  involved,  associated 
with  poor  nutrition,  and  possibly  to  a  greater  extent  upon  the  toxic 
effects  of  poisons  generated  within  the  blood  or  arising  from  other 
causes  and  acting  themselves  as  causes  of  the  existing  anemia. 

CHLOROSIS. 

Synonyms. — Fcbris  Anuitoria;  Greensickness;  Morbus  Virgineiis; 
Chlorcmia;    Chloraneniia;    Bleiclisucht  (German). 

Chlorosis  is  almost  exclusively  a  disease  of  young  women,  marked  by 
moderate  reduction  in  the  number  of  erythrocytes  and  greater  diminu- 
tion of  the  hemoglobin. 

Causes. — As  just  stated,  the  disease  is  practically  restricted  to  women, 
and  is  most  frequent  between  the  ages  of  fourteen  and  eighteen  years, 
although  it  occasionally  appears  later  in  life  {chlorosis  tarda).  A  con- 
dition closely  resembling  chlorosis  is  sometimes  seen  in  men.  A  family 
tendency  to  tuberculosis,  faulty  hematogenic  power,  or  heredity,  as  indi- 
cated by  cases  appearing  in  successive  generations,  may  be  predisposing 
factors.  Emotions,  such  as  grief,  fear,  anxiety,  homesickness,  and  disap- 
pointed love,  have  been  regarded  as  causes.  Hypoplasia  of  the  heart 
and  greater  vessels,  and  sometimes  of  the  generative  organs,  has  been 
observed.  Autointoxication,  constipation,  menstrual  disturbances,  un- 
sanitary surroundings,  overwork,  and  faulty  or  insufficient  diet  may 
cause  or  predispose  toward  the  condition.  Hemorrhage,  as  by  epistaxis, 
menorrhagia,  and  bleeding  from  hemorrhoids,  the  intestines,  or  stomach, 
are  often  assigned  as  etiologic  factors.  Race  and  climate,  particularly 
among  civilized  nations,  seem  to  have  no  influence  upon  the  occurrence 
of  this  malady.  Lloyd  Jones  believes  that  the  disease  is  more  common 
in  girls  belonging  to  large  families,  and  that  it  not  uncommonly  con- 
stitutes part  of  a  general  condition  one  of  whose  manifestations  is 
unusual  fertility.  Grawitz  regards  the  disease  as  a  neurosis;  von 
Xoorden  and  Immermann  would  limit  the  term  chlorosis  to  a  congenital 
or  aquired  functional  weakness  of  the  hematopoietic  structures  de- 
pendent upon  the  lack  of  an  internal  secretion  of  the  sexual  organs. 
Dyspepsia  and  constipation  associated  with  the  disease  are  generally 
not  regarded  as  etiologic  factors,  although  one  of  the  toxic  theories 
(autointoxication)  is  based  upon  the  belief  that  the  blood  condition  is 
due  to  copremia  or  some  allied  state.  In  the  i»resent  state  of  our  knowl- 
edge theories  suggesting  an  infectious  origin  are  not  regarded  with  favor. 

Hlood  Changes. — The  blood  is  easily  ol)tained,  Hows  freely,  and  is 
usually  pale  in  color.  The  specific  gravity  of  the  serum  is  normal  or 
higher  than  normal,  while  the  diminished  hemoglobin  gives  an  un- 
usually low  (1040)  total  specific  gravity.  Alkalinity  may  he  slightly 
increased.  Coagulation  is  rapid.  There  is  an  oligocythemia  that  varies 
within  wide  limits,  and  is  not  commonly  marked,  oligochromemia  being 
the  most  evident  change.  In  mild  cases  the  erythrocytes  fall  to  eighty 
per  cent,  of  the  normal  and  the  hemoglobin  to  fifty  per  cent.;  in  more 
marked  instances  the  erythrocytes  aj^proach  fifty  per  cent,  of  the  nor- 
mal and  the  hemoglobin  thirty  per  cent,  or  less.     The  averages  of  the 


422  SPECIAL   PATHOLOGY. 

357  cases  of  Cabot^  and  Da  Costa-  are:  erythrocytes,  3,934,000;  hemo- 
globin, 43.6  per  cent.  Hayem  has  reported  a  case  in  which  the  red 
blood-cells  fell  to  twenty  per  cent,  and  the  hemoglobin  to  sixteen  per 
cent.  It  will  thus  be  seen  that  the  reduction  in  hemoglobin  is  always 
greater  than  the  corpuscular  reduction  (low  color-index).  In  about 
forty  per  cent,  of  the  cases  the  number  of  red  blood-cells  does  not  fall 
below  4,000,000.  The  erythrocytes  show  a  mean  reduction  in  diameter, 
and  are  strikingly  pale.  ^  Microcythemia,  poikilocytosis,  and  polychro- 
matophiha  are  present  to  a  varying  extent.  Nucleated  red  cells  are 
rarely  abundant,  although  occasionally  a  few  normoblasts  occur.  The 
presence  of  macroblasts  is  usually  regarded  as  an  unfavorable  sign. 
The  platelets  are  considerably  increased.  There  may  be  no  important 
change  in  the  leukocytes,  with  the  exception  of  the  occasional  occurrence 
of  myelocytes  in  grave  cases.  Relative  lymphocytosis  may  occur. 
(See  table,  pp.   428  and  429.) 

Associated  Lesions. — The  panniculus  adiposus  is  usually  abundant, 
and  the  general  nutrition,  aside  from  the  pallor,  seems  fair  or  even  good. 
The  pallor  of  all  the  tissues  may  be  striking.  Granular  and  fatty  changes 
occur  in  the  heart,  and  aortitis  is  occasionally  present.  Hypoplasia 
of  the  heart  and  aorta  has  already  been  mentioned.  Fatty  changes 
in  the  capillary,  renal,  and  gastric  cells  have  been  noted.  Venous  and 
capillary  thrombosis  and  thrombosis  within  the  cranial  sinuses  not  in- 
frequently occur.  The  morbid  anatomy  and  blood  changes  fail  to 
explain  the  pecuhar  venous  hum  observed  during  life.  Changes  in 
venous  caliber,  and  in  the  blood  itself,  as  causes  of  this  important 
phenomenon  deserve  mention,  although  the  demonstration  is  by  no 
means  satisfactory. 

PERNICIOUS  ANEMIA. 

Synonynus. — Addison's  Causeless  Anemia;  Idiopathic  Anemia; 
Essential  Anemia;  Progressive  Pernicious  Anemia;  Myelogenic  Anemia; 
Ganglionic  Anemia;    Ancematosis;    Biermer's  Disease. 

Pernicious  anemia  is  a  morbid  condition  associated  with  excessive 
hemolysis  and  inadequate  hematogenesis  (West),  and  for  which  no  suf- 
ficient' cause  has  been  demonstrated.  While  an  adequate  cause  has 
not  been  recognized,  certain  predisposing  elements  are  regarded  as 
important  factors  in  the  production  of  disease;  of  these  predisposing 
causes  the  following  may  be  mentioned:  pregnancy,  parturition,  star- 
vation, hemorrhage,  degeneration  of  the  mucous  membranes  of  the 
alimentary  canal,  and  intestinal  parasites,  especially  the  Dibothrioce- 
phalus  latus.  The  disease  is  more  frequent  in  adults,  although  cases  in 
children  have  been  reported.  Dana^  reports  a  case  which  he  believes 
justifies  the  conclusion  that  congenital  weakness  of  the  blood-making 
organs  mav  predispose  to  the  occurrence  of  pernicious  anemia. 

Blood  Changes. — ^The  blood  is  often  difficult  to  obtain,  pale,  and 
watery,  although  occasionally  it  assumes  a  coffee  or  chocolate  color. 
A  drop  forming  at  the  point  of  puncture  is  usually  not  rounded  and 
elevated,  as  normal,  but  flattened,  and  may  spread  over  the  adjacent 

*  "Clinical  Examination  of  the  Blood,"  5th  ed.,  1904. 
^  "Clinical  Heinatolog}^"  2d  ed.,   1905. 
^  "Med.  Rec,"  Dec.  i,  1900. 


THK    BI.OOI).  42.? 

surface.  Oligocvthemia  is  niarkc'<l:  Itlood  counts  below  1.000,000  are 
not  infreciuent.  while  a  count  as  low  as  1+3,000  has  been  reported 
by  Quincke.  Occasionally,  blood  counts  may.  for  a  time,  apy)roach 
the  normal,  rising  to  or  exceeding  5,000.000.  followed  by  relai)sc  and 
death.  Though  microcytes  are  present,  the  average  size  of  the  erythro- 
cyte is  increased,  and  may  reach  10  .",  or  even  11  /'.  Megalocytes 
possessing  diameters  between  10  /'  and  lO  /'  occur.  The  y)ercentage  of 
these  large  cells  in  severe  cases  may  range  from  forty  to  seventy,  and 
Ewing'  studied  a  case  in  which  at  least  ninety  per  cent,  of  the  cells  meas- 
ured from  II  II  to  16  //.  He  states  that  unless  at  least  thirty-three 
per  cent,  of  the  red  cells  are  distinctly  oversized,  the  diagnosis  of  per- 
nicious anemia  should  be  made  with  reserve.  Nucleated  red  cells  are 
present  at  some  time  during  the  course  of  essentially  every  case  of  y)er- 
nicious  anemia ;  in  the  great  majority  of  cases  megaloblasts  predominate 
over  the  smaller  forms.  Even  the  megaloblasts  are  usually  present 
in  verv  small  numbers,  and  a  prolonged  search  should  be  made  before 
their  absence  is  deemed  conclusive.  They  not  uncommonly  appear 
in  larger  numbers  shortlv  before  death,  and  for  this  reason  an  increase 
is  generallv  regarded  as  an  unfavorable  sign.  So-called  crises  occur  in 
which  an  unusuallv  large  number  of  normoblasts  may  be  thrown  intfj 
the  circulation,  followed" by  an  increase  in  the  number  of  red  cells.  Free 
nuclei  are  sometimes  present  in  the  blood,  and  occasionally  one  sees  a 
nucleus  with  shredded  protoplasm  containing  hemoglobin,  attached  to 
its  periphery.  Both  normal  and  abnormal  sized  red  cells  may  show 
polychromatic  reactions  or  granular  basophilia.  By  reason  of  the 
irregularities  in  the  size  and  contour  of  the  erythrocytes,  rouleaux 
formation  is  peculiar.  Oligochromemia  does  not  approach  in  extent 
the  oligocythemia.  The  relatively  high  color-index— not  infrerjuently 
above  the'  normal— is  usually  held  to  depend  Upon  the  large  number 
of  red  cells  the  diameter  of  which  exceeds  that  of  the  normal  erythro- 
cyte; and  as  the  more  marked  the  anemia,  the  more  abundant  such 
cells  become,  it  is  commonly  found  that  the  fall  in  corpuscles 
is  not  associated  with  a  corresponding  fall  in  hemoglobin,  and  that 
the  corpuscular  count  mav  be  ten  per  cent,  of  the  normal  or  less,  and 
the  hemoglobin  from  fifteen  to  twenty  per  cent,  of  the  normal  or  more. 
The  specific  gravity  of  the  total  blood  is  decreased;  the  platelets  are  some- 
times increased,  and  occasionally  show  peculiar  and  excessive  aggluti- 
nation. The  leukocytes  are  usually  decreased  and  pronounced  leuko- 
penia is  not  uncommon;  accompanying  this  in  the  majority  of  cases 
is  a  relative  lymphocytosis.  Myelocytes  are  almost  constantly  present, 
but  in  small  numbers,  rarelv  exceeding  two  or  three  per  cent,  of  all  the 
leukocytes.  Leukolvsis  and  tinting  of  the  protoplasm  of  the  white  cells 
by  hemoglobin  mavbe  recognized  in  some  cases.  So  far  as  the  blood- 
y)icture  is  concerned  the  present  conception  of  the  disease  is  that  it  is  a 
megaloblastic  anemia.  The  term  "aplastic  anemia"  has  been  applied 
to  cases  clinically  resembling  yiernicious  anemia  but  in  which  regenera- 
tive changes  in  'the  bone-marrow  arc  inconspicuous  or  lacking.  (See 
table,  pp.  428  and  429.)  .     . 

Associated   Lesions.— \r\   spite   of   the   extreme   anemia,   emaciation 
is  not  present.     The  skin  is  pale,  but  mav  show  a  faint  icterus;  a  peculiar 
lemon  hue  may  be  manifest  in  the  conjunctiva.     Petechuc  are  occasion- 
•  "Clinical  Patholof:r>"  of  the  Blood."  2d  ed..  190J. 


424  SPECIAL  PATHOLOGY. 

ally  present.  There  is  not  uncommonly  a  small  amount  of  edema,  par- 
ticularly in  the  lower  extremities.  The  panniculus  adiposus  mav  be 
abundant ;  it  is  usually  yellowish  in  color,  contrasting  strongly  with 
the  red  muscles.  Coagulation  of  the  blood  in  the  great  vessels  and  in 
the  heart  may  be  delayed  or  absent.  The  presence  of  free  hemoglobin 
in  the  blood-serum  and  in  the  serous  fluids  is  often  marked  and  may  be 
sufficient  to  stain  the  hands.  Fatty  and  granular  changes  occur  in  the 
heart. ^  Similar  degenerative  processes  are  occasionally  seen  in  the  arte- 
ries and  capillary  walls.  Atrophy  of  the  gastric  mucosa  has  been 
described.  The  spleen  and  kidneys  may  show  pigmentation.  Degenera- 
tive changes  occur  in  the  spinal  cord,  particularly  in  the  posterior  col- 
umns and  to  a  less  degree  in  the  lateral  tracts;  the  sclerosis  is  not  svs- 
temic,  although  it  may  appear  so.  The  bone-marrow  usually  shows 
reversion  to  the  fetal  state,  and  contains  a  large  number  of  nucleated 
hemoglobin-containing  cells  (erythroblasts);  the  larger  cells  may  show 
evidence  of  phagocytic  power.  The  liver  is  usually  enlarged  and  may 
be  fatty,  and  constantly  contains  an  excess  of  iron  derived  from  dis- 
integrated erythrocytes.  Normalty,  the  percentage  of  iron  in  the  liver 
is  from  0.078  to  0.12,  while  in  pernicious  anemia  it  not  uncommonly 
reaches  0.7.  The  iron  is  distributed  in  the  hepatic  cells  at  the  periphery 
of  the  lobule,  where  it  is  usually  abundant.  Occasionally,  an  excess  of 
iron  will  be  found  deeper  in  the  lobule,  and  at  times  the  interlobular 
tissue  may  contain  a  trace. - 

It  is  generally  conceded  that,  though  specific  hemolysins  have  not 
been  demonstrated,  pernicious  anemia,  essentially,  is  due  to  an  exces- 
sive hemolysis.  This  is  indicated  by  the  occurrence  of  disintegrated 
cells,  microcytosis,  polychromatophilia,  plasmorrhexis,  etc.;  the  hepatic 
changes  oft'er  additional  support  to  this  theory,  and  also  indicate  that 
the  hemolysis  occurs  within  the  portal  circulation.  The  large  percentage 
of  iron  in  the  liver  supports  this  view,  and  the  absence  of  hemoglobinuria 
would  indicate  that  the  hemoc3^tolysis  did  not  occur  in  the  general 
circulation. 


LEUKEMIA. 

Syno}iy}ns. — Leiikocythemia ;  Lymphadenia. 

In  this  disease  there  occurs  a  most  marked  increase  in  leukocytes, 
which,  while  it  varies  within  wide  limits,  is  usually  a  constant  feature 
throughout  the  disease.  Leukemia  is  occasionally  observed  in  the  lower 
animals,  notably  the  cat,  dog,  ox,  sheep,  and  hog. 

Causes. — Leukemia  may  occur  at  any  age.  It  is  most  frequent 
during  middle  life — thirty  to  fifty  years.  It  is  twice  as  frequent  in 
man  as  in  woman.  A  history  of  malaria  is  present  in  a  certain  per- 
centage of  cases.  Injury  to  the  spleen  is  sometimes  followed  by  leu- 
kemia. Pregnancy,  lactation,  rickets,  and  syphilis  sometimes  antedate 
the  appearance  of  s3'mptoms.  The  scanty  evidence  regarding  heredity 
does  not  favor  the  view  that  it  is  an  important  factor.  Certain  facts  in 
the  history  of  some  cases  would  indicate  the  possibility  of  its  being  an 
infectious  disorder,  but  though  protozoa  and  various  bacteria  have  been 
described  as  present  in  the  blood,  and  though  it  is  claimed  that  the  disease 

'See  Fig.  142.  p.  244. 

'For  demonstration  of  iron  in  tissues  see  p.  236. 


PLATl:    V 


13  ^.v«^' 


Spleno-Medi'li-ary  Lkikemm 

(  Triacid  Slain.) 

1  l"r->m  lia  Costa's  "  Clinical  HeinaloU>K>.  ") 


I.    Small  Lymphocyte. 

^  ^^'^^C.mu.'^t'ihi^^'eil  xvitli  llK-  nivelocyles.  lo,  ii,  and  12.  nulinR  llie  prcsciice  of  iieiuro- 
I>hilo  Kr  iniiif^  i"  «li<^'  latur,  and  their  absence  in  the  lymphocyte.  The  si/.e  an<l 
iiiu  liar  .  haracU-ristics  •>!  all  these  cells  are  practically  ihe  same. 

3    I.    Polynuclear  Neutrophiles. 

"  osinop  i^e.  ^i^^^^j,,  ^osinophile.  rupMired  durinR  the  preparation  of  the  specimen,  the 
yrainilesarc  peculiarly  arrauKcd  atx.ut  the  nucleus;  no  siRns  ol  protoplasm  are  dis- 
tiiiK'iishahle. 

h     Eosinophilic  Myelocyte. 

Note  llic  irrcKularitv  with  which  the  granule"!  are  stamort 

7    S   Q.  10.  11.  \2.  13,  14.  15'    Myelocytes.     1  \,-„/,.>p/ii/i,-.t  .         ,,  . 

These  cells  varv  Rreallv  in  size  1  compare  s  with  qi.  hut  they  .ill  have  --i" 
live  characteristics-a  lar/je  op.-ilescent   micleus  cont.iiniiiK   a  scanty  , 
work  embedded  in  a  cell  b.>dv  crowded  with  .lelicatc  neutrophd.    k:^  .n 
like  those  found  in  the  polvnucUar  neutrophdes.  3  and  4.      ihe 
tincllv  indinteJ  and  somewhat  ileiiser  than  that  of  the  other  nu 
prr.bahlv  represents  a  developmental  phase  of  the  myelocyte  just 
lion  into  a  typical  polynuclear  neutrophile. 

"  ^°^Tl°''e?ulirocvtes  (stained  oranKC)  show  many  c%idenc«  of  deformity.  «n  occasional 
me^Kiyt'riiiany  microcytes.  and  a  few  poikilocyles  bemg  pnsenl.  Polychromato- 
uhilia  is  absent. 

•^  1  !•"      I-       I    4HKH      //-I-    t 


TIIK    HLOOI).  425 

has  been  communicated  to  lower  animals,  the  evidence  must  he  regarded 
— for  the  ])resent.  at  least — as  incomplete;  experienced  investigators 
have  failed  to  demonstrate  bacteria  in  the  lilood,  and  by  them  inocula- 
tion in  animals  has  proved  futile.  By  some  the  process,  especially  in  the 
acute  cases,  is  regarded  as  allied  to  tumor  fomiation.  This  view  would 
regard  the  blood  as  a  tissue  the  intercellular  substance  of  which  is  fluid, 
and  the  added  cellular  elements  present  in  the  blood  would  be  consiilered 
tumor  cells.  The  fact  that  the  cells  invade  the  organs,  or  at  least  are 
found  infiltrating  various  organs  and  tissues,  is  adduced  to  support 
the  theory.  Nothing  satisfactory  in  the  way  of  demonstration  has  been 
given,  and  at  best  the  view  can  be  looked  upon  as  a  working  hypothesis 
only. 

Two  forms  of  the  disease  are  recognized — (i)  myelogenous  and  (2) 
lymphatic.  Clinically,  either  may  be  acute  or  chronic.  The  myel- 
ogenous is  almost  always  chronic;  the  lymphatic  is  not  infrequently 
acute. 

The  Blood  Condition. — When  the  number  of  leukocytes  is  large,  the 
blood  may  be  pale,  and  even  slightly  turbid,  and  marked  oligocythemia, 
with  associated  reduction  in  blood  coloring-matter,  may  give  rise  to 
a  thin,  watery  consistence,  and.  as  a  result  of  the  presence  of  a  large 
number  of  leukocytes,  a  yellowish  tint.  The  platelets  are  increased,  the 
alkalinity  lowered.  Coagulation  is  delayed,  and  this  delay  is  most  nota- 
l>le  in  the  presence  of  pronounced  oligocythemia  and  oligochromemia. 
The  actual  quantity  of  fibrin  present  is  said  to  be  increased.  The  two 
statements  are  reconciled  by  the  belief  that  peptone  is  present,  which, 
as  is  well  known,  delays  coagulation. 

Myelogenous  Leukemia  (Myeloid  Leukemia  or  Lciikocytheniia;  Mycl- 
eniia:  M ytlocyiheiniii). — The  total  number  of  leukocytes  shows  a  wide 
variation,  the  majority  of  cases  being  included  between  100,000  and 
500,000;  counts  between  the  latter  number  and  1,000,000  are  not  in- 
frequent, and  as  high  as  1,590,000  has  been  recorded.  The  average  in 
the  108  cases  of  Cabot  and  DaCosta  was  370,000.  The  enormous  addi- 
tion of  myelocytes  is  the  most  conspicuous  change  in  this  form  of  the 
disease.  These  cells  may  constitute  from  twenty  to  fifty  per  cent,  of 
the  leukocytes  present — a  percentage  never  approached  in  any  other 
form  of  leukocytosis.  They  vary  remarkably  in  size,  from  7  ,"  to  20  « 
or  more  in  diameter.  Owing  to  the  frequency  of  degenerative  changes 
in  the  leukocytes  in  this  disease,  the  differentiation  of  myelocytes  and 
lymphocytes  is  in  many  instances  very  difficult.  Mast  cells  with  coarse 
granules  are  almost  constantly  conspicuous,  ranging  from  one  to  ten 
per  cent.,  or  even  higher.  Next  to  the  myelocytes  they  are  probably 
the  most  important  diagnostic  feature.  There  is  a  marked  absolute 
increase  in  the  eosinophiles  and  polymorphonuclear  leukocytes,  although 
the  preponderance  of  myelocytes  materially  alters  the  percentage. 
Instead  of  from  sixty  to  seventy  per  cent,  of  the  leukocytes  belonging 
to  the  polymorphonuclear  group,  the  percentage  varies  between  ten 
and  fifty.  The  uninuclear  cells,  lymj^hoid  and  hyaline,  are  relatively 
diminished.      Mvelocytes  showing  karyokinesis  are  occasionally  present. 

The  red  cells  are  usually  diminished  in  number;  the  extent,  however, 
of  the  reduction  varies  in  different  cases,  and  more  or  less  at  different 
periods  in  the  history  of  any  given  case.  Sometimes  the  count  may 
be  normal;     in  other  cases  the  oligocythemia   n■|•l^•  1>f>  nmst    ni.irked. 


426  SPECIAL  PATHOLOGY. 

Eichhorst  has  reported  a  case  in  which  the  red  cells  were  reduced  to 
316,000  to  the  cubic  millimeter.  The  reduction  in  red  cells  proportion- 
ately reduces  the  hemoglobin;  marked  alterations  in  the  color-index 
are  not  uncommonly  present.  A  conspicuous  morphologic  change  is 
the  abundance  of  nucleated  red  cells.  Normoblasts  are  rarely  absent; 
microblasts  and  megaloblasts  are  never  so  abundant.  Poikilocytosis 
is  not  commonly  conspicuous.  The  blood-platelets  are  commonly  in- 
creased. Charcot-Leyden  crystals  are  occasionally  seen.  (See  table, 
pp.    428  and  429.) 

Lymphatic  Leukemia  {Lymphocythcmia;  Lyni phcmia) . — Leukocytosis 
is  not'  so  marked  as  in  myelogenous  leukemia.  The  total  count  of  leuko- 
cytes ranges  between  40,000  and  400,000,  rarely  exceeding  200,000  or 
250,000,  although  counts  of  more  than  1,000,000  have  been  reported. 
The  average  in  the  thirty-five  cases  of  Cabot  and  Da  Costa  was  255,000. 
The  leukocytes  most  abundant  in  this  form  are  the  uninuclear  cells; 
in  some  cases  the  lymphocyte,  in  others  the  hyaline  cell,  predominates. 
The  polymorphonuclear  cells  are  diminished ;  the  eosinophils  are  scanty 
or  absent.  Myelocytes,  if  present,  are  never  abundant.  Oligocythemia 
is  more  conspicuous  and  constant  in  this  form  of  leukemia.  The  count 
of  the  red  cells  may  show  from  1,000,000  to  2,000,000.  Abnormal  forms 
of  red  cells  correspond  to  the  degree  of  anemia.  Nucleated  erythrocytes 
are  not  so  numerous  as  in  the  myelogenous  form  of  the  disease.  (See 
table,  pp.  428  and  429.) 

In  the  chronic,  and  usual,  variety  of  this  form  of  leukemia  the  small 
lymphocyte  commonly  predominates,  although  the  large  lymphocyte  may 
be  in  excess.  The  average  is  about  ninety  per  cent,  of  the  entire  number 
of  leukocytes.     Atypic  forms  of  lymphocytes  are  often  numerous. 

The  acute  variety  terminates  fatally  within  a  few  weeks  or  months 
after  its  onset,  and  in  many  ways  resembles  an  acute  infection;  a  specific 
cause,  however,  has  not  yet  been  demonstrated.  In  the  greater  number 
of  cases  the  large  lymphocyte  predominates,  an  excessive  leukocytosis 
not  always  being  present.  Conspicuous  accompanying  lesions  are  cutane- 
ous, mucous,  and  visceral  hemorrhages,  and  ulcerative  stomatitis. 

The  names  given  to  the  different  forms  of  leukemia  are  not  based 
upon  changes  in  the  organs;  enlargement  of  the  lymph-nodes  is 
not  a  constant  feature  of  lymphatic  leukemia  and  marked  changes  in 
the  bone-marrow  may  be  present.  Changes  in  the  organs  usually  de- 
pend upon  the  duration  of  the  disease  rather  than  upon  the  character 
of  the  blood-cells,  being  more  marked  in  chronic  cases. 

The  spleen  may  be  greatly  enlarged,  weighing  as  much  as  eight 
kilos.  The  capsule  may  be  fibrous  or  even  cartilaginous.  The  shape 
of  the  organ  is  not  altered.  Infarcts  may  be  recognized  upon  the 
surface  or  on  section.  Associated  infectious  processes  produce  less 
softening  in  the  leukemic  organ  than  in  the  normal  spleen.  The  color 
of  the  pulp  is  further  influenced  by  the  number  of  red  .blood-cells,  and 
as  leukemic  patients  are  prone  to  hemorrhage,  a  pinkish  or  pale  pulp 
may  be  induced  thereby.  In  the  absence  of  such  condition  the  pulp 
is  usually  redder  than  normal.  The  extensive  intercalation  of  leuko- 
cytes may,  even  in  the  paler  pulp,  obscure  the  Malpighian  bodies.  As 
already  stated,  the  density  of  the  organ  is  more  marked  in  the  chronic 
form  of  the  disease.  Under  the  microscope  the  splenic  reticulum  may 
be  somewhat  increased,  although  it  is  not  commonly  much  in  excess  of 


HLAIL    VI. 


Lymphatic  I.ki  kkmia. 

(  Triaciti  Stain.) 

(From  Da  Costa's  "  Clinical  HfrnaloloKv"! 


1,2,  ^,  4.5,  ft.   Small  Lymphocytes.  .         . 

'      These  cells  show  a  ^reat  dirtcreme  in  the  inlensity  ol  tht-ir  t 

dye.    Thf  smallest  forms,  i.  .•,.», and  s.bi-iiig  rii  her  111  nucl' 

more  deeply  than  the  Uru«r.  3  and  6.     Compare  2  with  th.  1 
-   S.  Q.  ID.  II,.  Large  Lymphocytes.  ,         1         u 

Except  in  10.  which  shows  a  delicate  rim  of  luchsin-stained  protoplasm,  theto  lx;mpho 

cvtes  appear  simpiv  as  pairchromatin-deticient  nuclear  structures,  lackiiiR  icll  bodus 

Conipan-  these  cells  with  the  myeUxrytes,  Plate  \  . 

"^"rhVupoer  cd^e'of  the  nucleus  is  somewhat   indented  and  the  protoplasm  i»  diMm 
guishable;  othersvise  this  cell  resembles  a  large  lymphocyte. 

(E.  F.  Fabf.r.  />.i 


THIC   HI.OOI).  427 

the  normal.  ( Jcc-asionally,  it  shows  more  or  less  hyaline  change.  The 
most  striking  feature  is  the  abundance  of  leukocytes.  These  are  usually 
of  the  form  in  excess  in  the  Mood.  The  more  chronic  the  case  and 
the  greater  the  splenic  enlargement,  the  more  marked  the  leukocytic 
intercalation. 

The  changes  seen  in  the  bone-marrow  usually  assume  f)ne  of  tw(; 
types,  although  intermediate  grades  are  occasionally  notctl.  Both  of 
these  tvi)es  have  received  inappropriate  names.  Pyoid  niorrmu  is  yel- 
lowish in  color  and  soft  in  consistence.  The  marrow  usually  present  is 
firm,  pink  or  pinkish-gray  in  color,  and  is  called  adenoid  or  lymphoid 
ntarrcnc.  The  abnormal  marrow  displaces  the  fatty  medulla  of  the  long 
bones.  Histologic  changes  of  the  myelogenous  form  consist  of  an 
enormous  increase  in  the  number  of  normal  marrow-cells.  Erythroblasts, 
normal  in  size,  and  cells  of  the  larger  and  smaller  types,  are  usually 
found;  large  phagocytic  marrow-cells  are  present.  Evident  cell  pro- 
liferation is  not  uncommonly  present,  and  in  a  few  cases  has  been  con- 
spicuous. The  gross  appearance  of  the  marrow  in  lymphatic  leukemia 
does  not  differ  from  that  observed  in  the  myelogenous  cases.  The  Icuko- 
cvtes  present  are,  however,  of  the  hyaline  and  lym])hocytic  types — nor- 
mal marrow-cells  being  displaced  by  the  lymphoid  intiliration. 

Lymph-nodes. — In  nearly  all  cases  of  lymphatic  leukemia  enlarge- 
ment of  these  structures  occurs  at  some  time  or  other  in  the  progress 
of  the  disease.  In  some  cases  the  enlargement  is  restricted  to  an 
anatomic  group;  in  other  cases  different  areas  may  be  involved;  and 
still  less  frequently  the  condition  may  be  general.  On  section,  the 
affected  nodes  are  pink  or  grayish-pink  in  color,  soft,  and  juicy.  Con- 
fluence is  not  common,  and  even  where  a  large  group  has  apparently 
merged  into  a  single  mass,  differentiation  of  the  nodes  may  be  possible. 
The  enlargement  of  the  nodes  seems  to  be  due  to  engorgement  of  the 
lymph-channels,  including  the  peripheral  sinuses.  In  the  less  frequent 
glandular  enlargement  of  the  splenomedullary  form  the  lymphatic  sin- 
uses are  distended  by  leukocytes  presumably  coming  from  the   blood. 

The  liver  usually  shows  considerable  enlargement,  and  may  weigh 
as  much  as  eight  kilos.  It  is  commonly  pale,  and  the  pallor  may 
be  most  conspicuous  along  the  course  of  the  portal  channels.  The  ex- 
treme anemic  appearance  is  frequently  due  to  the  intercalation  of  leuko- 
cytes, the  distribution  of  which  may  be  patchy,  local,  or  general. 

The  kidneys  may  be  enlarged,  and  lymphoid  intercalation  may  be 
marked. 

Increase  in  the  lymphoid  tissue  is  always  noticed  in  the  thymus  and 
the  lymphoid  elements  of  the  alimentary  canal,  as  well  as  in  the  lungs, 
and  even  in  the  skin.  The  tendency  toward  hemorrhage,  previously 
remarked  upon  as  a  clinical  yjhenomenon  of  leukemia  in  general,  is 
further  shown  by  the  occurrence  of  visceral  hemorrhage  and  of  hemor- 
rhage into  the  newly  formed  areas  of  lymphoid  tissue,  into  the  joints, 
and  even  into  the  brain. 

Xo  satisfactory  ex])lanation  has  been  offered  for  the  increase  in 
leukocytes  and  the  associated  intercalation  of  these  cells  in  the  various 
organs.  It  has  been  held  that  the  leukocytic  increase  is  dependent 
upon  proliferation  of  the  lymphoid  tissue  from  which  leukocytes  are 
thrown  into  the  general  circulation.  It  has  also  been  maintained  that 
the  lymphocytic  infiltration  of  the  various  organs  and  tissues  represents 


TABULATION  OF  BLOOD 


DISEASES. 


Chlorosis. 


Pernicious 
Anemia. 


Simple 
Primary 

Anemia. 


Gross  Appear- 
ance AND  Sp.  Gr. 


Hemoglobin  and 
Color  Index. 


Number  of 
Erythrocytes. 


Size  of,  and 
Form  Changes 
IN  Red  Cells. 


Blood  flows  readily..  Hemoglobin  greatly!  Normal   or    slightly  Decreased    in    size. 
Pale   red,  watery. |       reduced.     Color,       reduced.  i       Poilcilocytosisonly 

inde.x     constantly  in     severe     cases. 


Extravascular  co 
agulationslow;  in 
travascular,  fre- 
quent. Sp.  gr.  of 
total  blood  de- 
creased. Sp.  gr. 
of  plasma  slightly 
increased. 


low. 


Blood  flows  scantily,    Marked  reduction  in   Pronounced  oligocy 


to 


often  difficult 
obtain.  Watery, 
pale  red  (often  cof- 
fee color).  Coagu- 
lation slow.  Sp 
gr.  decreased. 


t  h  e  amount  o  f 
hemoglobin.  Color 
index  usuallyhigh. 


and  rarel  V  marked . 


themia.  Rouleaux 
formation  scanty 
or  absent. 


Myelog- 
enous 
Leukemia. 


Paler  red  than  nor-   Hemoglobin   moder-'  Moderately 
mal.     Coagulation       ately     reduced.       ished. 
slighdymore  rapid.       Color  index    nor- 
Sp.  gr.  decreased.  mal  or  nearly  so. 


dimin- 


Marked  variation  in 
.size.  Macrocytes 
predominate.  Poi- 
kilocytosis  more 
marked  than  in 
any  other  anemia. 


Light  red  or  milky. 
Less  fluid,  coagu- 
lation slow.  Sp. 
gr.  decreased.  Al- 
kalinity usually 
diminished. 


Hemoglobin  slightly  Usually  only  a  slight 
reduced.     Co)  or       reduction, 
inde.x    below  nor 
mal. 


Normal    or    slightly 
decreased  in  size. 


Lymphatic 
Leukemia. 


Pseudo-leu- 
kemia OR 
Hodgkin's 
Disease. 


Resembles  myelog-  Hemoglobin  reduc 
enous  type,  except  tion  more  marked 
that  changes  are  than  in  spleno 
not  so  pronounced.  medullary  type 
Alkalinity  usually.  Color  index  low. 
diminished. 


A  slight  reduction; 
poikilocytosis 
slight. 


Reduced,  .-Mways'  Reduction  in  size, 
more  pronounced i  and  distortion 
than  in  myelog-  more  striking  than 
enous  type.  i      in  myelogenous 

type. 


Paler  red  than  nor-  Hemoglobin  reduced.  Diminished, depend-;  May  be  undersized, 

mal,  depending  on       depending  on   se-  ing    on   severity|      Poikilocytosis     in 

severity.      Coagu-       verity  and    stage.  and  stage.               |      severe  cases, 
lation  more  raoid.'      Color  index    nor- 


Splenic  1 
Anemia. 


SECONDARY 
ANEMIAS. 


Sp.  gr.  normal  or 
slightly  decreased. 


mal  or  low. 


Pale  red.  more  wat-  Hemoglobin  reduced, 
ery.     Coagulation       Color  index    nor- 
more  rapid.      Sp.        mal  or  low. 
gr.  decreased. 


Pale  red,  depending  Reduction  varies, 
onseverity,  wat-;  depending  on  se- 
ery.  Coagulation!  verity.  Color  in- 
usually  rapid. i  dex  usually  below 
Sp.  gr.  decreased.]      normal. 


Reduced  sometimes!  Normal;  usually 
to  one-fourth  of  slightly  reduced, 
normal.  Poikilocytosis  sel- 

dom excessive. 


Diminution      vaiies   Usually     decreased, 
with  condition.  Poikilocytosis  in  a 

number  of  serere 
1      conditions. 


'  By  some  authors  not  recognized  as  a  primary  anemia. 


428 


CHANGES  IN   ANEMIAS. 


Npcleated 
Red  Cells. 


Xl'mblk 

LECKOCVTi::^. 


\(  ..K  ANi>  Small 

LVMPHOCVTKS. 


P0L\-M0R- 
PHOSLTLKAK 
LnUKOt  YTKS. 


.MVKI.OCYTKS. 


Ht.M.P 
PLATELETS 


R.irely  found.      Nor-   Generally  nor-   Occasionally  re  la 
moblasts  arc  prcs-       mal.  lively  inircast-d. 

cm  in  severe  c.iscs 


Normal  or  rcia     Rarely  found, 
lively     diniin 
ishc<l. 


lDcr«ue<l. 


Usually       relatively 
increased. 

Commonly    dc-   Small     number 
creased,    rela-        nearly     always 
tively.                    found. 

Microblasts,    normo- 
IJasts,  and    mcg- 
aloblasts    present. 
The    latter    most 
numerous. 

.\  moderate  leu- 
kopenia   may 
be  present. 

Dimini-Oied. 

Only  in  severe  cases. 

Generally     nor- 
mal. 

Sometimes  increased 
relatively. 

Increased,   but  rela- 
tively diminished. 

Sometimes     de-   Absent  or  rare. 

creased     rela- 

riv.h. 

Increased. 

More  frequent   than 
in   any  other  form 
of  anemia.      Nor- 
moblasts predomi- 
nate. 

Enormous      in- 
crease.   In  no 
other    anemia 
arc  leukocytes 
so  abundant. 

Increased,     but,  Myelocytes   form    a 
relatively    di-      large  percentage  of 
minished.              the  I  eu  kocy  t  es, 
from  10   to  60  per 
cent. or   more. 
(Basophilic  cells 
included.) 

Increased. 

Rarely  present. 

Greatly    >n-  Greatly  increased  (as 
creased,      but       high  as  90  per  cent 
not  to  the  ex-        or  moreV      Some- 
tent  found   in       times    small     and 
the      myelog        other  times   large 
enous  type.            are  increased. 

Relatively      de-'  Absent  or  rare, 
creased. 

Increased. 

Usually  absent.   May 
be     present     when 
disease  is  marked. 

Normal      or 
slightly  in- 
creased. 

.\  0 r m  a  1        or 
slightly  in- 
creased. 

Generally  normal. 

Generally  nor-    Rarely  found, 
mal. 

Increa.»e<l 

Rarely  present. 

Gencr.Jly       normal. 
I'sually    increxscd 

if   f,.^,.^  U  ,.n---nt 

Generally  nor      Rarely  found, 
mal. 

Incrca»c<l. 

Rarely  met  with    in 
mild  anemias,  but 
not  uncommon   in 
pronounced  cases. 

Generally      i  n  ■ 
creased.     Sel- 
dom  normal 
or  decreased. 

Usually  diminished. 

Usually     in      May   l»e    found    in 
creased .                  .some  cases. 

Usually   in 
crcajcd. 

430  SPECIAL  PATHOLOGY. 

the  accumulation  of  leukocytes  deposited  from  the  blood.  White  and 
Hopkins  favor  the  belief  that  the  increase  in  leukocytes  results  from 
diminished  destruction  of  the  cells. 

Pseudoleukemia  (Hodgkin's  Disease). — ^This  morbid  condition  resem- 
bles leukemia  in  its  anatomy,  but  differs  materially  in  the  blood  changes. 
The  latter  are  not  characteristic,  the  chief  value  of  the  blood  examination 
lying  in  the  absolute  exclusion  of  leukemia.  In  the  earl}^  stages  the 
blood  shows  no  noteworthy  departure  from  the  normal ;  later  a  variable 
degree  of  anemia  ensues.  The  leukocytes  remain  unchanged  or  moder- 
ately increased;  there  may  be  a  relative  gain  in  polymorphonuclear 
leukocytes  or  in  the  lymphocytes.  Like  leukemia,  the  disease  may 
assume  an  acute  form,  but  usually  is  chronic  in  type.  Splenic  enlarge- 
ment may  predominate  over  the  changes  in  the  lymph-nodes.^ 

Splenic  anemia — sometimes  called  pseudoleukemia  splenica — is  re- 
garded by  some  as  a  splenic  form  of  Hodgkin's  disease  analogous  to 
the  myelogenous  form  of  leukemia.  The  anemia  is  of  the  chlorotic 
type.  Leukopenia,  sometimes  pronounced,  is  the  most  characteristic 
finding.  Relative  lymphocytosis  is  common.  The  changes  in  the  blood 
in  pseudoleukemia  and  in  splenic  anemia,  and  their  differentiation  from 
leukocythemia,  will  be  found  in  the  table  on  pages  428  and  429. 

Mycoses  of  the  Blood  (see  Intoxications  and  Infections,  pp.  376  and 
377).- — The  possible  infections  of  the  blood  may  be  greater  than  is  at 
present  believed.  The  organisms  of  anthrax,  tuberculosis,  glanders, 
typhoid  fever,  and  relapsing  fever,  also  the  pyogenic  and  a  few  other 
bacteria,  have  been  identified  in  the  blood.  Care  must  be  used  in  draw- 
ing conclusions  from  the  presence  of  bacteria  in  the  blood  postmortem, 
as  it  has  been  satisfactorily  demonstrated  that  in  the  agonal  period — 
the  final  moments  or,  it  may  be,  hours  of  the  death  agony — bacterial 
diffusion  is  favored  by  the  lessening  bactericidal  action  of  the  blood 
and  the  probable  ^increasing  permeability  of  the  vessel  walls.  The 
demonstration  of  bacteria  in  the  blood  does  not  materially  differ  from 
their  demonstration  elsewhere.  Trustworthy  conclusions  are  rarely 
possible  from  an  examination  of  a  drop  of  blood  obtained  by  simply 
pricking  the  skin,  as  already  directed.  The  method  of  Sittmann  is  to 
be  commended.  A  vein,  preferably  one  in  the  arm,  is  exposed  under 
the  most  rigid  aseptic  methods,- — previous  sterilization  of  the  skin,  instru- 
ments, operator's  hands,  etc., — and  a  sterile  cannula  is  thrust  into  the 
vessel,  which  may  be  caused  to  distend  by  proximal  obstruction,  as 
by  pressure  by  the  finger  or  a  fillet  applied  above  the  point  elected  for 
opening.  The  blood  flowing  from  the  cannula  is  received  in  a  sterile  con- 
tainer (flask  or  test-tube  sterilized  by  heat),  and  the  subsequent  examina- 
tion is  conducted  upon  principles  laid  down  in  the  chapter  on  Bacterio- 
logic  Technic. 

Animal  Parasites. — The  animal  parasites  found  in  the  blood  are 
broadly  classed  as  hematozoa.  The  most  important  are  the  malarial 
organism  (p.  186),  the  embryo  of  the  Filaria  sanguinis  hominis  (p.  207), 
the  trypanosoma  (p.  183),  the  spirochasta  of  relapsing  fever  (p.  172), 
and  the  Distoma  hjematoba  (p.  193).  The  last  named  is  really  a 
parasite  of  certain  vessels — the  portal  vein  and  its  branches  and  the 
venous  ramifications  around  the  bladder  and  rectum. 

'  For  further  consideration  of  the  morbid  anatomy  of  Hodgkin's  disease  see 
Diseases  of  the  Lymph-nodes. 


CHAPTER   II. 
SPLEEN.' 

The  spleen,  in  the  course  of  the  postmortem,  is  the  first  organ  ex- 
amined m  the  abdominal  cavity.  It  varies  greatly  in  size  and  weight, 
usually  weighing  between  loo  gm.  and  350  gm.,  and  measuring  from 
10  cm.  to  15  cm.  in  length,  b  cm.  to  10  cm.  in  breadth,  and  2.5  cm.  to 
4  cm.  in  thickness;  the  relation  to  the  weight  of  the  body  is  about  i 
to  360.  The  color  varies  considerably,  even  in  health,  and  undergoes 
important  changes  after  death :   the  same  may  be  said  of  the  consistency. 

Postmortem  Changes  in  the  Spleen. — In  the  presence  of  any  engorge- 
ment or  necrotic  process  the  spleen  quickly  undergoes  postmortem 
disintegration.  As  a  result  of  attachment  to  the  stomach,  digestion 
may  give  rise  to  disintegration  of  the  gastric  wall  which  sometimes 
extends  into  the  splenic  tissue.  Sulphureted  hydrogen  passing  through 
the  wall  of  any  adjacent  hollow  viscus  gives  rise  to  precipitation  of  the 
iron  present  in  the  splenic  tissue,  as  a  result  of  which  the  organ  shows 
pscndomclatiosis,  at  first  restricted  to  the  area  of  contact,  but  in  time, 
and  particularly  where  decomposition  is  in  progress,  involving  the 
whole  surface  of  the  organ.  The  layer  of  postmortem  pigmentation  is 
usually  thin,  rarely  extending  to  a  depth  of  one  centimeter. 

Emphysema  of  the  spleen,  with  or  without  the  presence  of  gas  cysts, 
is  a  postmortem  process,  and  depends  upon  the  evolution  of  gas  in  the 
splenic  pulp  as  a  result  of  infection  by  some  gas-producing  organism, 
such  as  the  Bacillu.-^  ca]>sulatus  aerogenes,  colon  bacillus,  etc. 

Malposition. — Splenoptosis,  ii.\iniieriiig  or  )noi<able  spleen,  arises  as  a 
result  of  relaxation  or  stretching  of  its  normal  attachments,  and  usually 
the  organ  is  one  of  several  displaced  in  the  condition  called  splanchnop- 
tosis,- visceroptosis,  enteroptosis,  or  Glcnard's  disease.  Visceral  prolapse, 
of  which  splenoptosis  is  a  type,  may  result  from  developmental  defects, 
external  compression,  as  by  improper  corsets  and  belts,  or  may  occur 
in  patients  who  have  been  bed-ridden,  in  whom  it  is  a  result  of  muscular 
wasting  and  relaxation.  The  postpartum  cases  are  due  to  overdisten- 
tion  of  the  abdominal  wall  by  a  number  of  pregnancies.  Postoperative 
forms  result  from  similar  relaxation  of  the  belly  wall.  The  spleen  may 
also  be  displaced  by  blows  or  injuries  which  suddenly  force  the  costal 
margin  inward.  It  is  not  improbable  that  falls  in  the  erect  posture  or 
on  the  buttocks  may  jar  the  spleen  from  position.  The  extent  of  the 
splenic  displacement  may  be  very  marked,  the  viscus  at  times  becoming 
a  pelvic  organ.  It  is  probable  that  the  lengthening  of  the  suspensor>' 
ligament  mav  be  caused  by  an  increase  in  the  size  of  the  spleen,  and. 

'  Lectures  on  Disorders  of  the  Spleen.  Taylor,  "  Lancet."  May  2S,  IQ04.  n    1477. 

'  Robinson,  '  Phila.  Med.  Jour.,"  Nov.  30,  1901.  Keith.  "Lancet,"  Niarch  7. 
1903,  p.  631.  Brown,  "Amer.  Med."  •A.ug.  15.  1003.  Aug.  22,  1903.  "  —  <nd 
Aug.  29.  1903,  p.  350.      McCallum,  "Brit    Nied.  Jour."  Feb.  18,  1905,  ;  -  il- 

lant,  "International  ClinitS."  nio^,  vol    iv.  14th  .series. 


432  SPECIAL  PATHOLOGY. 

most  certainly,  the  displaced  organ  becomes  larger,  the  increase  in  size 
being  partly  due  to  the  obstruction  to  venous  return,  brought  about 
by  the  tension  on  the  splenic  vein  impeding  the  flow  of  blood  on  its 
way  to  the  liver. 

The  condition  is  more  common  in  the  female  than  in  the  male,  and 
is  most  frequent  in  women  who  have  borne  a  number  of  children.  Re- 
laxation of  the  abdominal  wall  favors  displacement  of  the  organ  by 
partial  withdrawal  of  its  normal  support.  The  spleen  may  be  forced 
from  its  normal  position  by  spinal  curvature,  tumors  and  swelling  in 
the  retrosplenic  area,  and  assumes  a  lower  level  as  a  result  of  inflamma- 
tory effusion,  morbid  growths,  etc.,  in  the  left  pleura.  The  organ  is 
sometimes  pulled  out  of  place  by  attachment  to  an  adjacent  prolapsed 
viscus,  as  the  colon,  stomach,  kidney,  or  pancreas.  The  long  pedicle 
necessary  for  such  marked  displacement  as  is  seen  when  the  spleen  is 
located  in  the  pelvis  or  in  the  right  iliac  fossa  is  usually  made  up  of  the 
splenic  artery  and  vein,  with  a  certain  amount  of  connective  tissue,  in 
which  may  be  embedded  a  part  of  the  pancreas.  The  danger  in  wander- 
ing spleen  is  twisting  of  the  pedicle  and  obstruction  to  the  blood-supply 
of  the  displaced  organ.  Interference  with  the  venous  circulation  may  be 
brought  about,  slowly  inducing  congestion,  with  marked  induration  of 
the  spleen  {cyanotic  induration).  It  is  alleged  that  the  interference  with 
circulation  may  give  rise  to  atrophy,  although  I  have  never  seen  the  two 
conditions  associated.  When  the  obstruction,  either  venous  or  arterial, 
-S  coraplete,  necrosis,  which  may  be  manifested  as  a  general  softening 
of  the  organ  or  as  gangrene,  occurs.  The  liability  of  wandering  spleen 
to  circulatory  disturbance  is  further  evinced  by  the  fact  that  it  not  un- 
commonly contains  infarcts;  these  may  be  of  different  ages.  As  a 
result  of  localized  peritoneal  inflammation  and  capsulitis,  the  wandering 
spleen  may  become  attached  in  some  abnormal  position,  and  has  been 
mistaken  for  a  neoplasm  arising  at  the  point  of  attachment. 

In  addition  to  the  wandering  spleen,  there  is  occasionally  seen,  as 
in  the  liver,  a  partial  rotation  of  the  organ  on  its  long  axis,  thus  pre- 
senting an  edge  for  percussion  and  other  physical  examination,  and 
misleading  the  clinician  as  to  the  size  of  the  organ.  In  the  situs  inversus 
the  organ  is  absent,  prolapsed,  or  on  the  right  side. 

Malformation. — The  spleen  may  be  absent.  Hypoplasia  of  the 
organ  is  more  common.  Spleuciili,  or  accessory  spleens,  are  quite  fre- 
quent. The  number  of  splenculi  varies.  Usuallv  one  or  two  are  found. 
Instances  have  been  reported,  however,  in  which  as  many  as  forty 
accessory  spleens  were  present.  It  is  probable  that,  in  the  cases  where 
hundreds  of  splenculi^  have  been  reported,  hemolymph  nodes,  normal 
or  enlarged,  have  been  mistaken  for  spleens.  The  accessory  organs  may 
be  situated  near  the  hilum  of  the  normal  organ,  in  the  splenic  pedicle, 
in  some  peritoneal  fold  adjacent  to  the  spleen,  or  even  upon  the  opposite 
side  of  the  abdominal  cavity.  Rarely,  they  are  found  in  the  spleen  itself, 
and  are  occasionally  embedded  in  other  organs,  as  the  pancreas.  Histo- 
logically, the  structure  of  the  accessory  organs  is  identical  with  that 
of  the  normal  viscus,  the  former  being  nothing  more  than  miniature 
reproductions  of  the  latter.  They  are  probably  physiologically  accessory 
to  the  normal  spleen,  and  may  undergo  hypertrophy  after  removal  of 
the  fully  formed  organ.  It  has  usually  been  found  that  where  animals 
'  "Miinch.  med.  "Woch.,"   1S95,  ^"0.   18,  p.  433. 


SPLEEN, 


433 


show  no  disturlianco  oi  lu-alih  as  a  result  of  syjlenectomy,  accessory 
spleens  have  hypcrlrophietl  and  have  assumed  the  function  of  the  re- 
moved organ. 

Instead  of  a  single  organ  ai)proaching  the"  normal,  with  a  numher 
of  accessory  spleens,  there  are  sometimes  found  two  or  more  smaller 
organs  of  approximatcI\'  the  same  size,  multiple  spleens.  Garrod  has 
observed  nine  spleens  in  one  cadaver.  Multi])le  and  accessory  spleens 
are  liable  to  the  same  diseases  as  the  normal  organ. 

The  normal  splenic  notch  may  in  rare  instances  be  absent,  and  in 
other  cases  a  number  of  notches  are  found.  Occasionally,  the  normal 
notches  are  deep,  and  practically  amount  to  incisures  or  fissures,  giving 
rise  to  the  bifid  splccti  or  lobiilatcd  splcoi. 

Atrophy  of  the  spleen  is  seen  particularly  in  the  aged.  The  typical 
senile  splco!  IS  usually  small,  with  a  wrinkled  capsule,  which  may  be 
considerably  thickened.  In  the  absence  of  any  preceding  or  associated 
condition  giving  rise  to  pigmentation  the  organ  is  usually  pale.     The 


Fig.  230. — Splke.v  Co.nsisti.vi;  of  Two  Parts  JoiNtu  by  t'lBRors  Hand. 
Each  half  contains  an  accessory  spleen  partly  emlx'dded  in  the  posterior  margin. 

Malpighian  bodies  and  splenic  pulp  are  atrophied,  and  the  fibrous  septa 
are  thickened.  A  closely  allied,  but  by  no  means  identical,  condition 
is  found  in  large  spleens  with  atrophied  Malpighian  bodies  and  intensely 
hyperemic  pulp.  As  a  result  of  fibrous  change,  a  certain  aiiiount  of 
contraction  may  be  present.  Little  is  known  of  true  hypertrophy  of 
this  organ.  By  some  the  enlargement  of  the  Sf)leen  seen  in  splenic 
anemia,  Hodgkin's  disease,  and  leukemia  is  held  to  be  an  example  of 
hypertrophy.  The  increase  in  size  seen  in  malaria  is  surely  not  hyper- 
trophic in  character.  I  would  hesitate  to  regard  as  hypertrophy  the 
splenic  enlargement  seen  in  many  infections,  infarction,  passive  conges- 
tion, lardaceous  disease,  cysts,  tumors,  etc.,  all  of  which  conditions  are 
clearly  distinct  from  true  hypertrophy. 

Pigmentary  Infiltration. —In  chronic  malaria'  the  spleen  may  acquire 
an  enormous  size  and  be  intensely  pigmentrd      The  viscus  may  weigh 

'See  Craig.    "Amcr.   .Mtd  ,"  July  25,   1903,   :  Keferences  to  previous 

papers. 
29 


434 


SPECIAL  PATHOLOGY. 


as  much  as  five  kilos,  or  even  more.  During  the  earher  infections 
the  spleen  is  soft,  the  pulp  being  almost  diffluent  and  of  a  dark-brown 
chocolate  color.  Thrombosis  of  the  smaller  blood-vessels  and  areas  of 
necrosis  are  not  infrequently  present.  Later,  or  after  repeated  infec- 
tions, the  organ  becomes  greatly  enlarged,  firmer,  cutting  with  consider- 
able resistance,  as  a  result  of  a  decided  increase  in  the  fibrous  tissue 
("ague  cake").  It  may  be  of  a  dark  slate-color,  due  to  the  contained 
pigment.  Histologically,  the  fibrous  septa,  the  trabeculae,  and  the  pulp 
all  show  an  abundant  increase,  with  wide-spread  deposit  of  melanin 
throughout  the  connective  tissue  and  pulp.  The  parasite  of  malaria 
may  be  found  in  the  spleen,  and  leukocytes  containing  the  organism  are 
not  infrequentlv  present. 

Lardaceous  Disease. — The  spleen  is  large,  and  may  be  volummous, 
weighing  five  kilos ;  it  is  lighter  in  color  and  of  higher  specific  gravity 
than  in  health,  and  contains  deposits  of  amyloid  material  in  sago-grain- 
hke  bodies;  hence  the  name,  sago-splccn.  The  iodin  reaction  renders  its 
recognition  clear.  (See  Lardaceous  Disease,  p.  228.)  Under  the  micro- 
scope the  lardacein  will  be  seen  to  occupy  the  Malpighian  bodies;  in 
the  eariiest  stage  it  probably  occurs  as  an  involvement  of  the  arterial 
branch  that  the  Malpighian  body  surrounds.  There  is  a  form  of  amyloid 
spleen  in  which  the  infiltration  is  more  diffuse,  not  in  the  distinct  sago 
grains,  as  just  described,  but  involving  the  pulp  and  fibrous  septa.  The 
chemic  reaction  is  equallv  well  marked,  but  is  more  diffuse  and  less 
punctiform  than  in  the  sago-spleen.  (See  Plate  IV.)  As  already  de- 
scribed, amyloid  disease  arises  in  a  number  of  organs  almost  simultane- 
ously, but  the  spleen  seems  to  suffer  most  in  the  early  stage  of  the 
wide-spread  morbid  condition,  and,  for  this  reason,  any  large,  rather 
pale  organ  should  be  carefully  tested  with  iodin  to  differentiate  clearly 
between  the  enlargements  due,  for  example,  to  leukemia,  and  those 
of  amyloid  disease.  The  occasional  deposit  of  hyaline  material  in  the 
septa,  vascular  twigs,  and  reticulum  has  been  regarded  as  a  form  of  de- 
generation.    It  is  possiblv  but  a  step  in  the  evolution  of  lardacein. 

Calcareous  infiltration 'is  seen  in  the  spleen  as  a  result  of  past  necroses, 
inflammations,  or  chronic  infections.  Lime  salts  are  not  infrequently 
deposited  in  the  thickened  capsule  of  chronic  capsulitis,  which  may 
extend  over  a  considerable  area  and  assume  a  bony  or  stone-like  hard- 
ness. The  periphery  of  quiescent  tuberculous  areas,  cyst -walls,  and  the 
cicatrices  of  old  infarcts  mav  show  calcareous  infiltration. 

Acute  Splenic  Tumor,  Splenic  Engorgement.— In  acute  sepsis,  and 
in  manv  of  the  acute  infectious  diseases  with  bacteria  or  their  products 
circulating  in  the  blood,  the  spleen  seems  to  become  distended  with 
blood;  its  pulp  grows  soft  and  diffluent,  and  the  whole  organ  becomes 
edematous  and  enlarged.  This  has  been  considered  by  some  an  acute 
engorgement, — an  acute  hyperplasia  of  the  organ, — the  result  of  the 
accumulation  of  toxic  bodies,  and  by  others  a  reactionary  phenomenon 
by  which  the  spleen,  accessory  to  other  organs,  is  enlarged  m  an  effort 
to  combat  infection.  As  we  are  not  fully  aware  of  the  functions  of  the 
spleen  or  of  the  organs  at  work  in  combating  infections,  the  precise 
cause  of  the  process  can  not,  for  the  present,  be  definitely  explained. 

The  condition  has  been  called  acute  diffuse  splenitis.  The  term 
engorgement  is  not  the  proper  one,  and  the  term  infectious  splenitis 
has  been  offered  as  a  substitute;  the  objections  to  the  latter  will  be- 
come apparent  when  considering  splenic  infarction. 


SPLEEN. 


435 


In  addition  in  llic  jjross  chani^cs  previously  noted ,  the  tension  of 
the  capsule  may  he  striking,  i\,nd  during'  life  it  may  he  so  jjreat  that, 
with  the  softenini(,  the  spleen  may  rupture.  Postmortem,  such  an  organ 
is  rarely  removetl  without  a  tear  in  its  ca]:)sule  through  which  the  ab- 
normally dark,  grumous  pulp  is  easily  expressed.  Such  an  organ 
will  show,  under  the  microscope,  a  pulp  distended  with  blood,  an  enor- 
mous number  of  leukocytes,  and  red  cells,  many  of  the  latter  frag- 
mented. If  bacteria  are  circulating  in  the  l)lo()d,  the  splenic  inter- 
stices may  be  distended  by  the  invaders.  The  pulj)-cells  may  be  found 
in  all  stages  of  their  life  history — karyokinetic,  active,  cloudv,  granular, 
and  fragmenting;  the  displaced  and  softened  fibnnis  network  manifests 
the  separation  of  fibers  incident  to  edema  and  vascular  distention. 
Commonly,  the  splenic  pulp  contains  a  large  number  of  phagocytes 
in  which  may  be  found  bacteria.  Some  of  the  phagocytic  cells  are 
leukocytes,  others  are  derived  from  the  large  endothelial  cells  lining  the 
pulp  sinuses;  many  of  the  phagocytes  contain  erythrocytes.  Areas 
of  focal  necrosis  are  practically  always  present,  and  in  some  of  these 
fibrin  may  be  demonstrated.  That  the  condition  is  not  alwavs  an  in- 
fection is  shown  by  the  fact  that  it  can  be  produced  by  abrin,  ricin,  and 
by  large  doses  of  sodium  nitrate.  These  considerations,  with  other 
clinical  and  experimental  data  at  hand,  would  lead  us  to  regard  the 
change  as  depending  upon  a  toxemia.  That  all  toxic  conditions  do 
not  bring  about  the  change  is  shown  by  its  absence  in  uremia.  There 
can  be  no  doubt  that  such  organs  recover;  the  changes  observed  in  the 
splenic  enlargement  of  typhoid  abundantly  establish  this  fact;  but  the 
exact  method  of  repair,  of  restoration,  and  of  regeneration  is  not  known. 

Chronic  diffuse  splenitis,  chronic  splenic  tumor,  chronic  splenic 
induration,  and  fibr(U<i  spleen  are  names  applied  to  a  condition  in  which 
the  organ  is  denser  than  normal,  frequently,  although  not  invariably, 
pigmented,  the  capsule  thickened  and  the  fibrous  tissue  of  the  splenic 
substance  notably  increased.  The  condition  is  seen  particularlv  in 
malaria,  and  includes  the  manifestation  called  ague  cake,  to  which  refer- 
ence has  been  made.  (Occasionally  the  splenic  enlargements  associated 
with  chronic  infectious  diseases,  particularly  syphilis  and  tuberculosis, 
possess  some  features  of  the  typical  fibroid  spleen.  Chronic  conges- 
tion of  the  spleen  due  to  circulator}'  deficiency,  as  in  cardiac  and  pul- 
monary disease  with  venous  retardation,  cirrhosis  of  the  liver,  and 
thrombosis  of  the  splenic  vein,  frequently  gives  rise  to  more  or  less 
fibroid  change  in  the  organ.  Prolapsed  spleens  contain  an  excess  of 
fibrous  tissue.  The  gross  appearance  of  the  organ  is  largely  determined 
by  the  presence  or  absence  of  pigmentation  and  the  extent  and  dura- 
tion of  any  associated  congestion.  When  jiigmented.  the  spleen  may  be 
brownish,  slate-colored,  or  gray;  congestion  also  renders  the  organ  dark. 
Typical  fibroid  spleens  are  sometimes  pale,  particularly  when  pigmenta- 
tion and  congestion  are  absent.  The  consistency  is  always  increased,  the 
organ  resists  incision,  and  is  perceptibly  firmer  than  normal,  sometimes 
quite  hard.  Histologically  the  most  noteworthy  change  is  the  marked 
increase  in  fibrous  tissue,  wliich  may  be  consj)icuous  even  within  the 
Malpighian  bodies.  The  endothelial  cells  are  often  prominent  and 
usually  pigmented.  From  the  thickened  capsule  the  broadened  fibrous 
septa  and  coarser  trabeculae  may  often  be  traced  to  the  hilum  of  the 
organ.  In  some  cases  the  hyperplasi.-i  involves  l„ith  imiIt.  .tnd  nti.  ulmn 
These  organs  avfi  usually  softer. 


436  SPECIAL  PATHOLOGY. 

Local  Splenic  fibrosis  develops  in  areas  of  past  infarcts,  in  the  neigh- 
borhood of  old  abscesses  and  cysts,  and  around  gummata  and  chronic 
tuberculomata  of  the  organ.  It  is  possible  that  some  splenic  scars  are 
due  to  the  cicatrization  of  necrotic  areas  of  traumatic  origin. 

Perisplenitis. — In  general  peritoneal  inflammation  the  serous  cover- 
ing of  the  spleen  is,  of  course,  involved.  By  extension  of  inflammation 
from  some  adjacent  tissue  or  viscus^such  as  the  stomach  in  chronic 
ulcerative  processes,  the  diaphragm  in  pleurisy  of  the  left  side,  peri- 
nephric inflammations,  and  chronic  colitis  involving  the  splenic  flexure 
of  the  colon — the  capsule  of  the  spleen  may  become  inflamed  and  thick- 
ened, and  may  form  adhesions.  Rarely  is  this  observed  as  an  acute 
process,  but,  rather,  the  results  are  seen  postmortem.  The  whole  of 
the  capsule  may  be  involved  (capsular  fibrosis),  or  only  a  small  area, 
circumscribed  capsulitis;  the  past  inflammation  is  marked  by  a  layer  of 
formative  tissue  from  2  mm.  to  10  mm.  in  thickness,  rarely  thicker, 
and  usually  adherent  to  some  adjacent  structure — diaphragm,  colon, 
stomach,  or  posterior  abdominal  wall.  On  external  examination  the 
white  area,  if  small,  may  resemble  the  scar  of  a  past  infarct;  but  on 
section  its  purely  capsular  relation  will  be  apparent.  In  some  instances 
the  newly  formed  fibrous  tissue  is  piled  up  in  layers,  constituting  the 
so-called  lamellar  or  corneal  fibroma  of  the  spleen.  In  rare  instances 
the  new  tissue  is  cartilaginous.  Sometimes  the  capsular  inflammation 
and  its  associated  thickening  extend  along  the  fibrous  septa  down- 
ward into  the  spleen.  When  the  capsulitis  has  been  uniformly  dis- 
seminated over  the  whole  organ,  the  mass,  before  section,  may  not 
resemble  the  spleen :  during  operation  it  has  been  mistaken  for  a  tumor ; 
its  position,  relations,  and  attachments  during  life  should  prevent  such 
an  error,  and  an  incision  postmortem  quickly  exposes  the  character- 
istic splenic  parenchyma.  It  is  possible  that  the  uniformly  thickened 
capsule  might,  by  contraction,  lead  to  atrophy  of  the  splenic  structure, 
but  it  is  not  known  that  such  a  process  ever  occurs  to  a  sufficient  extent 
to  involve  the  function  of  the  organ. 

In  cirrhosis  of  the  liver  with  obstructed  portal  circulation,  in  pro- 
lapsed and  wandering  spleens,  in  cardiac  or  pulmonary  disease  associated 
with  venous  engorgement,  and  during  or  after  thrombosis  of  the  splenic 
vein,  more  or  less  passive  congestion  of  the  spleen  occurs.  The  organ 
becomes  large,  soft,  sometimes  semifluctuating,  and  nearly  always 
dark  in  color;  later,  it  may  be  rather  fibroid.  The  condition  is  anal- 
ogous to  the  changes  in  the  cyanotic  kidney.  There  is  usually  a  decided 
increase  in  the  fibrous  tissue,  distended  blood-vessels,  edematous  and 
rather  fluid  pulp,  and  considerable  pigmentation. 

Hemorrhage  into  the  splenic  pulp  occurs  in  nearly  all  infections 
that  prove  fatal,  and  is,  therefore,  usually  demonstrable  in  any  spleen 
showing  engorgement  of  the  kind  described  on  page  434.  As  a  result 
of  injury  during  delivery,  and  sometimes  in  the  infections  that  follow, 
splenic  hemorrhage  is  seen.  It  also  occurs  in  the  new-born  as  a  mani- 
festation of  congenital  syphilis.  The  hemorrhage  may  be  diffuse  or 
focal.  Focal  hemorrhages  are  commonly  multiple,  and  vary  in  size 
from  I  mm.  or  2  mm.  to  accumulations  as  large  as  an  orange.  Little  is 
known  of  the  changes  that  take  place  in  areas  of  hemorrhage  occurring 
in  patients  who  recover.  It  is  probable  that  the  blood  is  absorbed, 
and  that  more  or  less  fibrous  tissue  results.     Marked  increase  in  the 


SPLEEN.  437 

contained  picjment    is  practically    always    present,  but    is  usually    not 
sutVuicntlv  circuniscrihed  to  identity  the  area  positively. 

Splenic  Infarction. — In  no  orjj[an  more  clearly  than  in  the  spleen 
are  to  be  seen  the  results  of  Iodised  cmlioli.  The  vessels  to  the  spleen 
are  characteristically  terminal,  and  their  distribution  and  ending  in 
the  splenic  pulp  are  such  that  no  embolus  is  likely  to  traverse  the  organ 
without  being  arrested.  Simple  emboli  induce  infarcts,  distinctly 
conoid  or  irregular;  on  section,  wedge-shaped;  with,  in  the  early  stages  of 
the  process,  an  elevated  surface;  in  color  purplish  (hemorrhagic  infarcts), 
black,  or  of  a  combined  tint;  soft  at  first,  later  firm,  and,  again,  after 
coagulation  has  terminated  in  liquefaction  necrosis,  soft,  semifluid,  or 
even  cvstic  in  consistency.'  Later,  if  not  too  large,  organization  and 
cicatricial  tissue  formation  convert  the  mass  into  a  pale  and  eventually 
white  cone  of  scar  tissue  extending  more  or  less  deeply  into  the  paren- 
chvma  of  the  organ;  sometimes  such  a  scar  extends  to  the  hilum, 
almost  dividing  the  organ  into  two  parts.  In  other  cases  the  infarct 
contains  but  little  blood;  it  does  not  become  purplish  or  black,  as  in 
the  foregoing,  but  is  of  a  light  pink,  pinkish-white,  or  whitish  hue,  and 
hence  is  called  anemic  or  ivliite  infarct.-  There  is  the  same  coagulation 
necrosis,  followed  by  liquefaction  necrosis,  and  probably  the  result  is 
the  same  as  in  the  area  of  the  hemorrhagic  infarct.  The  number  of 
infarcts  may  be  so  great  as  to  preclude  counting;  as  a  rule,  more  than 
one  are  present.  While  usually  on  the  surface,  they  are  not  always 
superficial,  and,  while  most  frequently  the  area  involved  is  cone-shaped, 
the  blending  of  a  number  of  infarcts  may  offer  so  misleading  a  picture 
as  to  require  careful  study  for  positive  identification. 

Infected  emboli  quickly  produce  an  entirely  different  picture.  Prob- 
ablv,  in  the  early  development  of  the  infarct,  the  appearance  is  the  same; 
soon,  however,  the  area  involved  is  converted  into  an  abscess,  and  as 
such  abscesses  are  usually  multiple,  the  spleen  becomes  studded  with 
small  pus  cavities,  or  may  show,  by  confluence,  one  or  more  of  much 
larger  size.  It  is  well  to  remember  that  the  soft,  juicy,  splenic  pulp, 
with  its  open-mouthed  blood-vessels,  may  contain  a  pus  in  which  leuko- 
cvtes.  necrotic  tissue,  and  extravasated  blood  are  so  commingled  that 
the  resulting  substance  lacks  the  macroscopic  appearance  of  pus. 

Splenic  abscess^  mav  also  arise  from  direct  injur}-  of  the  spleen  and 
from  extension  of  suppurative  processes  from  adjacent  organs,  such  as 
perforating  ulcer  of  the  stomach,  and  at  times  without  any  discernible 
cause.  The  occurrence  of  splenic  abscess  in  typhoiti  fever  and  other 
acute  processes  must  be  looked  upon  as  resulting  from  pyogenic  infec- 
tion of  an  area  of  necrosis,  itself  caused  by  the  activity  of  toxins  circu- 
lating in  the  l)lood.  It  is  admitted,  of  course,  that  the  typhoid  bacillus 
might  possibly  induce  suppuration  without  the  presence  of  pyogenic 
cocci.  Actinomycotic  and  gummatous  lesions  occasionally  suppurate. 
Manv  splenic  abscesses  are  preceded  by  malaria.  Splenic  suppuration 
may  follow  pelvic  or  appendicular  abscess.  Abscess  of  the  spleen  may 
be  single  or  multiple.  Embolic  abscesses  are  usually,  although  by 
no  means  always,  multiple.     Abscesses  resulting  from  trauma  and  from 

*  See  ¥i^.  152,  p.  282. 
'See  Infarction,  p.  281. 

»  Pince,  These,  de  Paris,  igo.j.  Stavely.  "Annals  of  Surgery.  June.  1903. 
p.  866.     Spear,  "Jour.  Amer.  Med.  Assoc    "  Autr    i     kjo;.  y.  ;o4. 


438  SPECIAL  PATHOLOGY. 

direct  invasion  of  the  splenic  tissues  are  commonly  solitary.  An  abscess 
mav  be  superficial  or  deep ;  its  shape  is  largely  dependent  upon  the  cause ; 
embolic  abscesses  are  usually  more  or  less  irregularly  conic,  and  trau- 
matic abscesses  are  commonly  ovoid  or  spheric.  The  pus  from  splenic 
abscess  is  usually  dirty-red  or  chocolate  color  and  frequently  contains 
shreds  or  necrotic  masses  of  splenic  tissue.  When  the  suppurative 
lesion  approaches  the  surface,  a  perisplenitis  results.  This  may  attach 
the  spleen  to  the  abdominal  wall  or  to  one  of  the  hollow  viscera.  An 
abscess  may  rupture  into  the  peritoneal  cavity,  into  some  adjacent 
hollow  viscus,  or,  where  the  process  is  limited,  inspissation  and  encap- 
sulation occasionall}^  occur. 

Thrombosis  of  the  splenic  vein,  while  rare,  may  occur,  giving  rise  to 
edema  and  distention  of  the  organ  resembling  the  congested  spleen; 
there  is  commonly  more  edema,  and,  as  the  process  is  acute,  less  fibrous 
tissue  is  present.  The  thrombus  may  be  an  extension  backward  from 
the  portal  vein,  or,  arising  in  the  splenic  vein,  may  extend  into  the 
portal. 

Gangrene  of  the  Spleen. — The  wandering  spleen  may,  by  twisting 
its  pedicle,  cut  off  the  blood-supply  and  blood  exit;  the  poisons  pro- 
duced by  the  disorganization  of  the  splenic  tissue  favor  the  migration 
of  bacteria  from  the  adjacent  alimentary  canal,  and,  by  this  infection, 
the  dissolution  of  the  organ  terminates  in  gangrene.  The  author  has 
known  two  cases,  undiagnosticated  during  life,  and  both  found  with  evi- 
dent infection  postmortem.  Gangrene  of  the  spleen  may  also  follow  em- 
bolism, thrombosis  of  the  splenic  vein,  pressure  by  neoplasms  or  pene- 
tration of  the  organ  by  necrosing  processes  begun  in  some  contiguous 
tissue. 

•The  term  splenomegaly^  has  been  applied  to  a  number  of  conditions 
having  in  common  a  splenic  enlargement  not  associated  with  a  recogniz- 
able type  of  infectious  disease,  and  not  including  the  enlarged  spleens 
of  leukemia  or  the  familiar  form  of  Hodgkin's  disease.  Those  cases  in 
which  the  enlargement  is  accompanied  by  anemia  have  been  called 
splenic  anemia  ;  in  these  the  organ  is  conspicuously  enlarged,  the  fibrous 
tissue  somewhat  increased,  and  there  is  marked  endothelial  hyperplasia. 
Herzog  suggests  that  the  proHferating  endothelial  cell  secretes  some 
erythrolytic  substance  through  the  activity  of  which  the  red  blood-cell 
destruction  is  accomplished.  An  interesting  feature  of  these  cases  is 
the  prompt  recovery  following  splenectomy.  In  another  group  of  cases 
the  spleen  is  enlarged  and  may  weigh  3  kilos ;  the  lowest  weight  recorded 

1  Banti,  "Ziegler's  Beitriige,"  1898,  xxiv,  p.  21;  also  "Rif.  Med.,"  March  i 
and  5,  1901.  Muir,  "Jour,  of  Path,  and  Bact.,"  Feb.,  1901.  Herzog.  "Chicago 
Path.  Soc,"  March  11",  1901.  Brill,  "Amer.  Jour,  of  Med.  Sci.,"  April,  1901,  p 
377.  Rolleston  and  Jones,  "Chir.  Soc.  of  London,"  Feb.  28,  1902.  Field,  "Amer 
Jour,  of  Med.  Sci.,"  March,  1902,  p.  405.  Azzurrini,  "  Lo  Sperimentale,"  1902 
Nos.  V,  vi.  Emile-Weil  and  Clerc,  "Arch.  Gen.  de  Med.,"  Nov.,  1902.  Morse 
"Boston  Med.  and  Surg.  Jour.,"  May  28,  1903.  Osier,  "Amer.  Jour,  of  Med 
Sci.,"  Aug.,  1903,  p.  187.  'Carpenter,' "Brit.  Med.  Jour.,"  Aug.  29,  1903,  p.  463 
Quenu  and  Duval,  "Revue  de  Chir.,"  Oct.  10,  1903,  p.  444-  Levison,  "Annals 
of  Siirgery,"  Nov.,  1903,  p.  671.  Borissowa.  "Virchow's  Arch.,"  1903,  Bd.  172. 
Osier, '"  Brit.  Med.  Jour.,"  Jan.  16,  1904,  p.  121.  Turk,  "Wien.  klin.  Woch," 
Feb.  II,  1904,  p.  15^3,  and  Feb.  18,  1904,  p.  189.  Weber  and  Watson,  "Clinical 
Soc.  of  London,"  March  11,  1904.  Stiirmer,  "Brit.  Jour,  of  Obst.,"  Oct.,  1904. 
Gilbert  and  Lereboullet  "Soc.  de  Biologic,"  Nov.  12,  1904.  Weintraud,  "Zeit. 
f.  klin.  Med.,"  vol.  55.  Brill,  Mandlebaum  and  Libman,  "Amer.  Jour,  of  Med. 
Sci.,"  March,   1905,  p.  491. 


SPLEEN'.  439 

is  over  boo  gm.,  and  the  average  of  the  reported  cases  over  1500  gm.; 
sooner  or  hiter  the  condition  is  followed  by  cirrhosis  of  the  hver. 
The  affection  is  called  Banti's  disease,  after  its  discoverer.  By  some 
observers  the  splenic  enlargement  that  follows  hei)atic  cirrhosis  is  cla.ssed 
with  splenomegaly.  According  to  Azzurrini,  the  changes  in  the  organ 
are  identical  witli  those  resulting  from  other  forms  of  stasis  affecting 
the  spleen.  The  veins  and  sinuses  are  dilated,  the  follicles  wasted, 
and  the  ervthrocyte  content  of  the  organ  is  enormously  increased. 
Under  the  name  of  primitive  splenomegaly  or  primary  epithelioma  of 
the  spleen  has  been  described  a  condition  m  which  the  organ  is  markedly 
enlarged,  firm,  and  contains  white  or  yellowish- white  areas  resulting 
from  hvperplasia  of  the  endothelial  cells  and  some  increase  in  the  fibrous 
tissue.  The  term  epithelioma,  sometimes  applied,  is  misleading,  and 
should  be  replaced  by  endothelial  hyperplasia;  as  the  evidence  of  tumor 
formation  is  not  convincing,  the  name  endothelioma  is  also  objectionable. 
In  still  another  group  of  cases  the  splenic  enlargement  is  associated  with 
polvcvthemia  and  proportionate  increase  in  the  hemoglobin — a  condi- 
tion to  which  reference  is  made  on  page  411.  In  this  condition  there 
is  marked  hvperplasia  of  the  pulp  and  endothelial  cells,  and,  like  the 
other  forms  of  splenomegaly,  is  not  explained  by  any  facts  with  which 
we  are  at  present  familiar.'  In  still  another  group  of  cases  the  splenic 
enlargement  is  clearlv  of  a  neoplastic  type  with  definite  tumor  forma- 
tion in  the  parenchyma  of  the  organ.  These,  cases  should  not  be  in- 
cluded with  the  forms  just  mentioned. 

Leukemia  and  Pseudoleukemia. — In  these  diseases  the  spleen  is 
often  much  enlarged,  pale  or  bright  red,  with  tense  capsule,  and  not 
uncommonlv  with  adhesions  to  the  adjacent  organs.  The  largest  spleens 
are  found  in  mvelogenous  leukemia,  in  which  disease  the  weight  of 
the  organ  mav  approach  8  or  9  kilos.  Accessory  spleens  usually  show 
enlargement. '  The  density  of  the  organ  seems  to  be  dependent  more 
upon  the  duration  of  the  process  than  upon  the  kind  of  leukemia. 
Infarcts  are  frequentlv  present,  and  are  often  of  different  ages.  In  some 
cases  the  Malpighian  bodies  stand  out  as  lightly  colored  nodules  on  the 
incised  surface,  so  clearly  enlarged  as  to  be  most  prominent  features; 
in  other  cases  the  cut  surface  is  uniform.  Under  the  microscope  the 
hvperplasia  seems  to  involve  the  entire  splenic  parenchyma  as  a  lymphoid 
cellular  growth,  either  shown,  as  previously  indicated,  by  overgrowth 
of  the  Malpighian  bodies  and  pulp,  the  former  in  excess,  or  of  both 
structures  without  apparent  differentiation.  In  leukemia  the  splenic 
enlargement  mav  be  largely  due  to  the  intercalation  of  leukocytes,  the 
added  white  cells  being  of  the  same  kind  as  those  found  in  excess  in 
the  blood.  In  other  cases  the  spleen  contains  definite  tumor-like  masses, 
sometimes  called  lymphoid  growths.  Such  tumors  var>-  in  size  from 
purely  microscopic  bodies  to  nodes  two  or  three  centimeters  in  diameter; 
thev  sometimes  project  on  the  surface  of  the  spleen.  (For  blood  con- 
dition in  leukemia  and  pseudoleukemia  see  pp.  424  and  430,  and  table 
on  pp.  42S  an<l  42().  1 

Rupture  of  the  Spleen.'— As  a  result  of  violence — either  directly  ap- 
'  Eisendrath,  "Jour.  Amer.  Med.  Assoc."  Oct.  25.  1902.  p.  1032;  also  ".\- 
of  Surgery."  Dec.  1902.     Editorial  in  "Lancet,"  Sept.  26.  1903.  p.  895-     ' 
"Med.  News,"  April  2^,  1904.  p.  780.     Da\-vs.  "Brit.  Med.  Jour..  "  May  7.  1.(^,4. 
p.  1077.     Auvray.  "Soc.  de  Chir.."  Nov.  9,  1904:   also  "La  Presse  .Mtd  , "  Jan.  11. 
1905.  p.  17. 


440  SPECIAL  PATHOLOGY. 

plied,  as  by  a  blow  or  fall,  or  transmitted,  as  by  the  sudden  arrest  of 
the  body,  as  in  falling  from  a  height — the  spleen  may  rupture;  when 
enlarged,  the  most  trifling  accident  may  be  followed  by  laceration,  and, 
when  intensely  engorged  or  softened,  as  in  infectious  diseases,  including 
malaria,  rupture  may  occur  without  recognizable  trauma — so-called  spon- 
taneous rnphire.  The  resulting  hemorrhage  is  likely  to  be  severe,  but 
is  not  invariably  fatal,  and  in  rare  instances,  with  small  stellate  tears, 
a  clot  may  form  and  the  organ  may  undergo  repair  by  the  subsequent 
formation  of  cicatricial  tissue.  Rupture  may  occur  in  areas  of  septic 
infarction,  splenic  abscesses,  and  cysts.  In  addition  to  true  rupture, 
which  necessarily  involves  the  capsule,  interstitial  or  subscapular  lacera- 
tions of  the  spleen  are  occasionally  observed;  these  may  be  attended 
by  circumscribed  or  diffuse  hemorrhages  into  the  parenchyma  and 
consequent  areas  of  necrosis,  and  are  sometimes  followed  by  cyst  forma- 
tion— so-called  metaclastic  cysts  of  the  spleen;  some  writers  include 
with  these  the  loculated  parasplenic  hemorrhages  that  sometimes  result 
from  injury  of  the  organ.  According  to  Brunswic-le-Bihan,^  the 
metaclastic  cysts  may  contain  eight  to  ten  liters  of  greenish,  sterile  fluid 
abounding  in  leukocytes  and  normal  and  altered  erythrocytes. 

Chronic  Infections  of  the  Spleen. — The  most  frequent  of  these  is 
tuberculosis.  According  to  x\uche,-  there  are  ten  recorded  cases  of 
primary  splenic  tuberculosis;  in  nine  of  these  the  lesions  were  chronic, 
caseous,  fibrocaseous,  or  calcareous  in  type.  Secondary  tuberculosis 
of  the  spleen  may  be  acute  or  chronic.  In  acute  general  miliary  tuber- 
culosis there  is  practically  always  an  almost  uniform  invasion  of  the 
splenic  tissues  with  typical  miliary  tubercles  located  near  the  arteries, 
in  the  pulp,  in  the  Malpighian  bodies,  or  even  in  the  capsule  of  the 
organ.  In  chronic  tuberculosis  of  the  spleen  the  organ  contains  one 
or  more,  rarely  many,  caseous  or  caseocalcareous  areas  5  mm.  to  5  cm. 
in  diameter  and  often  encapsulated.  The  smaller  nodules  may  be  com- 
pletely cretaceous,  constituting  one  form  of  the  so-called  splenic  calculus. 

Syphilis  of  the  spleen  occurs  in  two  forms — congenital  and  acquired. 
The  congenital  type  may  be  manifested  in  one  of  two  ways:  (i)  Diffuse 
splenic  fibrosis  with  some  enlargement,  which,  however,  is  not  usually 
marked,  although  Ziegler  records  an  instance  in  which  the  enlarged 
spleen  weighed  100  gm.  at  birth;  according  to  Marfan,  the  most  constant 
lesion  of  hereditary  syphilis  is  enlargement  of  the  spleen.  (2)  In  other 
cases  true  gummata  are  found.  The  splenic  lesions  of  acquired  syphilis 
var}^  with  the  stage  of  the  disease  during  which  the  organ  is  involved. 
In  the  earlier  stages  of  syphilis  the  spleen  may  participate  in  the  hyper- 
plasia found  in  a  number  of  the  blood-making  organs,  especially  the 
lymphoid  tissue ;  in  the  late  secondary  or  early  tertiary  period  a  diffuse 
fibrosis  is  not  infrequently  present ;  later,  the  characteristic  lesion  of 
tertiary  syphilis — the  gumma — is  occasionally  seen.  Commonly,  the 
lesion  is  solitary,  but  in  very  rare  cases  two  or  more  gummata  may  be 
found.  The  size  varies  greatly;  the  mass  is  spheric  or  oval,  of  a  pearly- 
white  or  grayish-white  color,  and  is  sometimes  translucent,  particularly 
at  the  margin.  Like  chronic  tuberculosis,  the  masses  are  sharply  de- 
fined at  their  margins,  but,  unlike  the  tuberculous  nodule,  caseation  is 
not  a  characteristic. 

^  "Revue  de  Chir.."  Nov.  10,  1904,  p.  64S. 

'  "Jour,  de  Med.  de  Bordeaux,"  June  2,  1901. 


SPLEEN'.  441 

Leprosy  of  the  splccti  manifests  itself  by  the  occurrence  of  nodules 
of  granulation  tissue  containing  lepra  cells  loaded  with  the  hacilli  in 
quite  characteristic  clusters. 

ActinoDiycosis  of  the  spleen  occasionally  occurs;  with  the  develop- 
ment of  the  actinomycotic  node,  suppuration  usually  ensues,  engendering 
an  actinomycotic  al)scess  of  the  organ. 

Tumors  of  the  Spleen. — Splenic  tumors  are  not  common.  The 
primary  tumors  in  an  otherwise  normal  spleen  are,  of  course,  connec- 
tive-tissue neoplasms;  of  the  adult  or  typical  series,  osteoma,  fibroma, 
and  lymphangioma  are  occasionally  observed;  cavernous  hemangiomata, 
which  may  be  multiple,  are  sometimes  encountered.'  Sarcoma  is  less 
rare.  Secondary  tumors  are  more  frequent  than  the  primary  growths, 
and  as  sarcoma  travels  by  the  blood-stream  more  frequently  than  car- 
cinoma, it  is  the  u.sual  secondary  neoplasm  of  the  spleen.  Cancer, 
however,  does  occur. 

Cysts-  of  the  Spleen. — Cysts  are  found  in  the  spleen  oftener  than 
primary  neoplasms.  They  may  result  from  the  encapsulation  of  massive 
infarcts,  or  areas  of  necrosis  resulting  from  injury,^  which,  by  reason 
of  their  size,  have  failed  to  organize  and  have  not  been  absorbed.  Some 
splenic  cysts  are  lymphangiomata.  The  usual  cyst  is,  however,  of 
parasitic  origin  (hydatid),  and  may  attain  considerable  size;  rarely,  the 
parasitic  cysts  of  the  spleen  are  multiple. 

'  See  Pumpelly,  "Med.  Record,"  Jan.  9,  1904,  p.  51,  and  Thiele,  "Virchow's 
Archives,"  Nov.  3,  1904,  p.  296. 

'  Otto.  Inaug.  Diss.,  Tubingen,  1904. 
'  See  Rupture  of  Spleen. 


CHAPTER  III. 
LYMPH-NODES. 1 

The  lymph-glands,  or,  more  appropriately,  the  lymph-nodes,-  are 
structurally  composed  of  a  peculiar  form  of  cell  which,  when  massed  to- 
gether, constitute  lymphoid  tissue ;  these,  in  the  node,  are  retained  in  place 
by  a  reticulum  of  connective  tissue.  The  lymph-node  lies  loosely  in  the 
connective  tissues,  and,  in  addition  to  its  blood-supply,  receives  through 
its  capsule  the  afferent  lymph-vessels,  draining  lymph  from  the  area  be- 
yond ;  after  passing  through  the  node  the  lymph  finds  its  exit  by  way  of 
the  efferent  vessel,  eventually  reaching  the. blood  through  the  vein  into 
which  the  Ivmph-vessel  empties.  The  capsule  of  the  node  is  composed 
of  fibrous  tissue,  with  some  unstriped  muscle-fibers;  from  the  capsule 
run  septa  that  converge  at  the  hilum,  dividing  the  node  into  follicles. 
Each  follicle  is  made  up  of  a  reticulum,  scaffolding,  or  sponge-like  net- 
work of  connective  tissue,  in  the  spaces  of  which  are  lodged  the  lymphoid 
cells;  toward  the  periphery  of  the  ovoid  follicle  the  lymphoid  cells  are 
smaller  than  in  the  center,  in  which  many  of  the  larger  form  show  active 
karyokinesis.  The  lymph,  in  passing  through  the  node,  is  in  intimate 
contact  with  the  cell's  of  the  parenchyma,  and  in  this  way  is  probably 
altered  in  composition  and  cellular  contents ;  at  the  same  time  the  node 
structure  is  exposed  to  whatever  deleterious  influences  the  lymph,  in  its 
return  to  the  circulation,  may  bring.  It  will  thus  appear  that  the  nodes 
may  be  influenced  by  the  blood  brought  to  them  and  by  the  lymph 
of  the  area  drained. 

The  hemolymph-nodes^  occupy  a  histologic  and  probably  a  func- 
tional position  intermediate  between  the  ordinary  lymph-nodes  and  the 
spleen.  Our  knowledge  concerning  these  structures  is  a  comparatively 
recent  acquisition,  and  we  are  as  vet  unfamiliar  with  many  phases  of 
their  pathologv.  Warthin  has  shown  that  they  increase  in  size  and 
that  new  nodes  are  developed  after  splenectomy.  In  pernicious  anemia 
the  blood-sinuses  dilate  and  the  endothelial  cells  engulf  erythrocytes 
and  frequently  become  pigmented;  in  some  cases  these  structures 
show  a  marked  hyperplasia. 

Lymphoid  Atrophy. — In  the  old  this  process  is  normal.  It  may  be 
a  metaplasia,  the  node  being  more  or  less  replaced  by  adipose  tissue. 

'  The  examination  of  the  lymph-nodes  during  a  postmortem  is  regional :  that 
is,  the  glands  of  an  area  are  examined  with  other  organs  of  the  region,  so  that  the 
consideration  of  their  special  patholog^'  at  this  point,  near  the  spleen,  is  due  to 
the  intimate  association  of  their  lesions  -with  those  of  the  spleen  rather  than  to 
any  special  propriety  of  considering  them  at  this  time. 

^  For  recent  study  of  the  histolog\'  of  lymph-nodes,  see  Bunting,  "Jour,  of 
Anat.  and  Physiol.,"  1905,  vol.  xxxix.  Part  3. 

^Warthin,  "Amer.  Jour,  of  Med.  Sci.,"  Sept.,  1902.  p.  674:  "Trans.  Chicago 
Path.  Soc,"  1902,  vol.  V,  No.  8.  p.  151;   also  "Proceed.  Path.  Soc.  of  Phila.,"  Dec, 

1903,  n.  s.,  vol.  vi.  No.   10,  p.   12.      Dayton,  "Amer.  Jour,  of  Med.  Sci.,"  March, 

1904,  p.  448.      Lewis.  "Jour,  of  Anat.  and  Physiol.."  1904,  vol.  xxxviii,  Part  3. 

442 


LYMPII-NODES.  443 

Such  nodes  are  usually    firmer  and    paler  than   normal.  l>ut   may    be 
])i_i,MiU'nted  and  dark. 

Pigmentary  Infiltration. — Whatever  pigment  the  lymph  may  find 
in  the  tissue  of  the  area  drained  is  brought  to  the  node,  and  may  be  de- 
posited (p.  231).  Thus,  in  the  removal  of  blood  extravasated  into  the 
connective  tissue,  the  coloring-matter  gathered  by  migrating  cells 
is  brought  to  the  node  by  the  afferent  vessels  and  deposited.  In 
anthracosis — indeed,  in  all  forms  of  pneumoconiosis — the  pigment 
from  the  lung  is  carried  to  the  adjacent  lymph-nodes,  where  it  may  be 
deposited  in  such  quantities  as  to  render  the  structure  brown,  gray,  slate- 
colored,  or  even  black.  Some  of  the  infiltrated  material,  as  certain 
calcium  salts,  may  be  removed;  other  solid  or  insoluble  bodies  may 
remain  as  a  permanent  piart  of  the  node.  The  infiltrated  material  may 
induce  a  chronic  indurative  inflammation  and  the  production  of  fibrous 
tissue,  thus  rendering  the  node  firmer,  larger,  and  less  efficient  in 
phvsiologic  activity  than  normal.  Whether  or  not  normal  lymph- 
nodes  are  likely  to  be  invaded  by  calcareous  matter  can  not  be  definitely 
settled,  but  certainly  an  inflamed  or  infected  gland  is  exceedingly  sub- 
ject to  the  deposit  of  lime  in  its  interior.  Bone  is  sometimes  found  in 
Ivmph-nodes'  and  in  the  tonsils;  in  the  latter  structures  Ruckert  be- 
lieves that  the  change  results  from  inclusion  of  fetal  cartilage  during 
development.  The  bone  found  in  the  lymph-nodes  may  be  due  to  a 
true  metaplasia  of  the  connective  tissues,  but  is  usually  associated  with 
tuberculosis  of  the  affected  structures.  It  may  be  superficial  (capsular) 
or  interstitial. 

Lardaceous  disease  affects  lymph-nodes  as  it  does  other  tissues  of 
the  bodv.  At  times  it  would  seem  that  there  may  be  lardaceous  de- 
posits in  the  nodes  of  an  area  without  manifest  general  deposition  in 
other  tissues.  This  is  said  to  arise  as  a  result  of  the  lymph  bringing 
to  the  node  a  material,  or  irritant,  which  leads  to  the  change,  and 
which,  being  arrested  in  the  node  involved,  permits  the  other  tissues 
to  escape.     (See  Amyloid  Disease,  p.  227.) 

Of  the  degenerative  changes  in  lymph-nodes  but  little  can  be  said. 
Thev  are  usuallv  due  to  irritants  brought  to  the  nodes,  and  occupy 
positions  of  secondary  importance.  It  would  seem,  however,  •  that 
hyaline  degeneration,  and  possibly  colloid  change,  may  occur  in  lymph- 
nodes  without  any  apparent  or  discoveraljle  antecedent  disease.  Both 
affect  the  vessels  and  reticulum  and  are  rarely  marked. 

Infections  of  Lymph-nodes. — These  structures,  probably  more  than 
anv  other  tissue,  possess  a  remarkable  susceptilnlity  to  the  influence 
of  bacteria  or  their  toxic  products.  There  is  hardly  a  known  infection, 
from  bubonic  plague,  which  seems  to  explode  its  virulence  on  the  lymph- 
nodes,  to  the  most  chronic  infection,  such  as  leprosy,  which  does  not 
either  directlv  or  indirectly  modify  the  structure  and  function  of  the 
lymphoid  tissues.  Edsall-  has  shown  that  even  in  typhoid  fever  the 
Ivmph-nodes  of  the  axilla,  neck,  or  groin  are  occasionally  perceptibly 
enlarged.  The  change  in  most  cases  is  an  inflammation,  a  lympliadctiitis, 
which  mav  extend  to  the  tissues  around  and  give  rise  to  a  pcrilymph- 
adcnitis.  As  to  time,  the  process  may  be  fulminatingly  acute,  or  may 
extend  over  months  or  even  years. 

'See  Lubarsch,   "Virchows  Arch,"    1904.   Bd.    177,  p.  371.     Also  Ruckert, 
ibid..  3S7.     Both  articles  also  deal  with  a  similar  change  in  the  tonsils. 
'     Amer.  Jour,  of  Med.  Sci."  April.  1904.  p.  599. 


444  SPECIAL  PATHOLOGY. 

In  the  lymphadenitis  arising  from  the  ordinary  infections,  such  as 
those  produced  by  the  pyogenic  bacteria,  the  appearance  of  the  node  is 
more  or  less  modified  according  to  the  stage  of  the  disease.  At  first  it  is 
swollen,  tense,  and  tender,  and  the  obstruction  to  the  passage  of  fluid 
through  the  node  may  be  evinced  by  a  surrounding  or  overlying  edema, 
or  a  swelling  in  the  tissues  of  the  area  drained.  On  section,  the  surface 
is  gray,  grayish-white,  or  pink,  or,  rarely,  there  may  be  enough  con- 
tained blood  to  give  the  incised  tissue  a  darker  hue.  In  a  node  not 
previously  indurated  the  parenchyma  is  soft,  and  may  be  diffluent. 
Under  the  microscope  the  lymph-channels  are  distended  by  leukocytes, 
and  commonly  contain  fibrin ;  in  the  follicles  areas  of  coagulation  necro- 
sis, containing  fragmented  endothelium  and  leukocytes,  are  usually  con- 
spicuous. Later,  the  necrosis  extends  beyond  the  follicles,  involving 
the  septa,  and  eventually  the  capsule  and  circumglandular  tissues. 
Such  an  inflammatory  and  necrotic  mass  constitutes  a  bubo.  Buboes 
are  common  in  the  groin  during  infectious  lesions  of  the  genitalia  and 
superficial  infections  of  the  lower  extremity,  in  the  axilla  from  similar 
lesions  affecting  the  arm,  hand,  or  mamma,  and  in  the  neck  when  the 
initial  process  is  in  the  superficial  tissues  of  the  scalp,  face,  mouth,  or 
pharynx.  One  must  not  forget  possible  unusual  lymphatic  distribution ; 
for  example,  cases  in  which  involvement  of  the  supraclavicular  nodes 
follows  disease  of  the  breast,  the  corresponding  axillary  structures 
escaping. 

Suppuration  of  the  lymph-nodes  fails  to  occur  in  many  infections, 
particularly  those  in  which  the  infecting  organism  does  not  possess  the 
faculty  of  pus  production.  In  these  cases  there  is  necrosis  of  the  lymph- 
oid tissue,  with  corresponding  interference  with  function.  Thus,  in 
diphtheria  the  toxins  absorbed  from  the  involved  area  give  rise  to 
edema  of  the  lymph-nodes,  coagulation  necrosis,  and  periadenoid  serous 
infiltration;  these  changes  probably  lessen  the  phagocytic,  bactericidal, 
or  other  protective  powers  of  the  lymphoid  tissues  to  such  an  extent  as 
to  permit  of  suppuration  should  pyogenic  bacteria  be  carried  into  the 
node.  The  somewhat  dense  capsule  of  lymph-nodes  permits  the  occur- 
rence of  a  rather  prolonged  intraglandular  inflammation  without  infec- 
tion -of  the  surrounding  tissue;  such  a  battle  between  the  invading 
organism  and  the  gland-cells  may  terminate  in  a  victory  for  the  latter, 
or  in  a  drawn  battle,  in  which  case  periadenoid  induration  and  subse- 
quent dense  fibrosis,  with  possible  calcareous  change,  may  so  surround 
the  area  of  danger  as  permanently  to  include  it  as  a  "healed-in"  focus. 
It  is  a  limitation  of  this  type  that  occurs  in  tuberculosis,  and,  though  less 
commonly,  in  actinomycosis,  glanders,  and  other  infections  that  attack 
the  lymphoid  tissues. 

The  slow  continuous  or  interrupted  delivery  to  the  lymph-nodes 
of  irritant  bodies,  such  as  may  be  derived  from  some  permanent  area 
of  infection  or  from  dust — as  in  pneumoconiosis  when  solid  particles 
are  being  constantly  brought  to  a  node — induces  a  more  or  less  sub- 
acute or  chronic  productive  change,  during  which  new  fibrous  tissue  may 
be  formed  in  and  around  the  node,  constituting  adenitis  chronica  or 
periadenitis  chronica,  or  the  two  lesions  combined. 

Of  the  chronic  infections  occurring  in  lymph-glands,  tuberculosis 
and  syphilis  are  the  most  important,  although  leprosy  may  involve 
the  lymphatics. 


LYMIMl-NODKS.  445 

Tuberculous  lymphadenitis,'  ihc  scrofulous  lymfyhaiknitis  or  scrofula 
of  the  okler  writers,  arises  from  invasion  of  the  lymph-nodes  by  the 
Viacillus  of  tuberculosis  brought  to  the  gland  by  the  lymph  or  blood. 
That  it  is  usually  lym])hogenous  can  not  1)6  doubted;  but  this  would 
not  account  for  those  occasional  cases,  really  rare,  ap])arently  no  sys- 
tem of  glands  in  the  l)ody  esca])ing,  and  in  which  affected  tissues  develop 
tuberculosis  at  so  nearly  the  same  time  as  to  preclude  the  belief  that 
the  initial  lesion  was  in  any  one  area.     It  may  be  possible  that  these 
cases  are  general  infections   directly  by  the  T)lood :    that  is,   tubercle 
bacilli    carried    throughout    the    organism    reached    the    lymph-spaces, 
and  from  these  were  transferred  to  the  lymph-nodes.     Whatever  may 
be  the  cause,  undoubted  cases  of  almost  universal  lymphatic  tul^ercu- 
losis  (Hcur.     The  frequent  form  of  the  affection  is  regional  tuberculous 
lymphadenitis  ;    in  this  form  the  disease  attacks  some  chain  of  lymph- 
nodes  in  such  a  manner  as  to  indicate  a  fairly  clear  source  or  route  of 
infection.     Under  this  head  come  ccrzical,  lucdiastiual,  mesenteric  and 
retroperitoneal,  axillary,   and  inguinal  lyniphadenoid  tuberculosis.     The 
route  of  invasion,  or,  rather,  the  portal  of  entry,  can  often  be  surmised, 
and.   although  rarelv,   at  times   demonstrated.     A  mucosa  weakened 
bv  inflammation  is  'usually  the  vulnerable  tissue  through  which  the 
irifection    occurs;   thus,    tuberculosis    of    the    cervical    lymph-nodes   is 
observed  to  follow  catarrhal  processes  affecting  the  nose  or  throat  or 
inflammatory    lesions    in    the    mouth.     The    frequency    of    mesenteric 
tuberculosis  in  bottle-fed  children,  in  whom  indigestion  and  catarrhal 
lesions  pave  the  way  for  the  entrance  of  the  bacillus  of  tuberculosis 
(admittedly  not  an  infrequent  milk  contaminant),  is  largely  explained 
bv  admitting  the  increased  permeability  of  an  already  diseased  mucosa. 
The  frequency  of  tuberculosis  of  the  mediastinal  nodes  following  in- 
fluenza is  siniilarly  explicable.     As  already  stated,  the  point  of  entry 
of  the  bacillus  can  sometimes  be  more  or  less  accurately  determined. 
Senn  reports  a  case  in  which  a  nontuberculous  girl  wore  the  earrings 
of  a  tuberculous  sister,   and  later  developed  a  local  tuberculous  out- 
break.    The  author  saw  a  case  of  axillary  tuberculosis  follow  a  wound 
made  bv  a  corset  steel  on  the  outer  margin  of  the  breast  in  a  young 
girl  nursing  a  sister  in  an  advanced  stage  of  tuberculosis  of  the  lungs ; 
the  glands  were  removed,  and  no  further  evidence  of  tuberculosis  has 
been  observed. 

Cervical  tuberculous  lymphadenitis  is  clearly  the  result  of  infection 
from  the  oral  and  pharyngeal  cavities.  Halle  found  that  in  3161  chil- 
dren with  enlarged  cervical  glands,  2334  had  carious  teeth;  and  of 
these,  1646  corresponded  in  location  with  the  enlarged  glands.  Oden- 
thal,  among  987  children,  found  decayed  teeth  in  429;  424  of  these 
had  enlarged  Ivmph-nodes.  Halle  demonstrated  that  if  cavities  in 
the  teeth  of  dogs  be  packed   with   Prussian  blue   and   cemented,  the 

'  Finkelstein,  "Vratch."  lune  2.  1901.  Sailer,  "  Phila.  Med.  Jour.,"  April  5 
and  12,  1902.  Mitchell,  '"Bulletin  of  Johns  Hopkins  Hospital,"  July,  1902. 
Rouiihton.  "Lancet,"  Oct.  iS,  1902,  p.  1032.  Dowd,  "Annals  of  Surgery,"  1903. 
Carr'iere.  "Zentralbl.  f.  innere  Med.,"  Tulv  11.  1903.  No.  2S.  Macfadyen  and 
Macconkev,  "Brit.  Med.  lour.."  lulv  18,  1903.  p.  129.  Weill  and  Pehu,  "Lyon 
Med  .  '  Aug.  9,  1903,  p.  22S.  Morf.  "N.  Y.  Med.  Jour.,"  Aug.  29,  1903,  p.  410. 
Hand.  •Proc.  Phila.  Path.  Soc,"  March,  1003,  p.  132.  WestenhoetTer,  "Berl. 
klin.  Woch.."  1904.  Bd.  xli.  Xos.  7  and  8.  Freeman,  "  N.  Y.  Acad,  of  Medicine," 
April  7.  1904.     Painter  and  Erving,  "Amer.  Med.,"  Sept.  24,  1904,  p.  539. 


446  SPECIAL   PATHOLOGY. 

pigment  may,  in  from  two  to  three  days,  be  present  in  the  nearest 
Ivmph-nodes.  Dieulafoy  and  others  have  shown  that  tonsils — fre- 
quently without  evidence  of  tuberculosis — may  contain  the  bacillus, 
and  that  the  organism  often  is  present  in  adenoids.^  All  observers  are 
agreed  that  glandular  infection  of  this  type  is  a  disease  of  childhood 
and  adolescence;  Finkelstein  found  it  in  456  cases;  329  of  the  patients 
were  between  ten  and  twenty  years  of  age.  In  Hand's  series  of  332 
autopsies  on  children,  115  had  tuberculosis;  of  these,  infection  appeared 
to  have  been  primary  in  the  bronchial  glands  in  75,  in  the  mesenteric 
nodes  in  10,  and  in  the  tonsil  in  i ;  in  the  remainder  it  was  not  possible 
to  say  at  what  point  infection  probably  occurred.  Mitchell  states 
that  a  family  history  of  tuberculosis  is  present  in  about  half  the  cases, 
and  that  less  than  five  per  cent,  of  those  affected  present  evidence  of 
pulmonary  involvement. 

JMorhid  Anatomy. — The  studies  of  Walsham  clearly  establish  that 
neither  macroscopically  nor  microscopically  is  it  possible  in  all  cases 
to  recognize  the  tuberculous  nature  of  the  affection;  the  anatomic 
character  of  the  lesion  is  so  varied  that  nothing  short  of  demonstrating 
the  bacillus  is  trustworthy.  The  condition  long  known  as  lymphoid 
or  endothelial  hyperplasia  of  the  lymph-nodes  is,  in  many  if  not  in  all 
cases,  a  manifestation  of  tuberculosis;  the  histologic  tubercle  is  fre- 
quently absent  and  often  there  is  no  cell  accumulation  resembling  such 
a  -structure.  In  these  cases  the  endothelial  cells  of  the  lymph-sinuses 
are  found  proliferating  and  the  mononuclear  elements  greatly  increased ; 
sometimes  fibrin  can  be  demonstrated  and  areas  of  necrosis  are  often 
present.  In  such  cases  the  diagnosis  of  tuberculosis  must  rest  upon 
the  identification  of  the  bacillus.  In  other  instances  the  diagnosis 
may  readily  be  made.  The  affected  nodes  are  very  much  enlarged, 
swollen,  and,  at  first,  not  attached  to  the  intervening  and  surround- 
ing tissues;  the  capsules  are  thin  and  tense.  On  incision,  early  in  the 
case,  the  node  is  more  or  less  hyaline,  translucent,  and  succulent; 
scattered  throughout  its  structures  tubercles  in  different  stages  of  de- 
velopment and  in  all  degrees  of  necrosis  and  degeneration,  may  be 
seen;  later,  these  bodies  may  become  fibroid,  caseous,  or  calcareous. 
In  the  mean  time  the  node  shrinks  in  size,  grows  fibroid,  and  develops 
a  dense  and  thickened  capsule.  Such  nodes  as  the  last-described 
represent  a  "healed-in"  tuberculosis,  or  quiescent  tuberculous  lymphad- 
enitis. In  less  favorable  instances  the  process  of  caseation  involves 
the  whole  node;  eventually,  a  periadenitis  is  induced,  and  the  node 
becomes  adherent  to  contiguous  structures;  masses  of  such  structures 
may  coalesce.  These  either  break  down  singly  or  a  number  caseate 
at  once,  giving  rise  to  a  tuberculous  abscess,  the  contents  of  which 
are  free  from  pyogenic  bacteria.  In  a  small  percentage  of  the  cases 
pyogenic  bacteria  may  have  gained  ingress  either  with  the  tubercle 
bacilli  or  as  a  secondary  infection;  under  such  circumstances  the  in- 
flammation will  be  attended  by  more  marked  systemic  phenomena  and 
the  suppurative  changes  will  be  more  conspicuous.  On  the  whole,  it 
may  be  said  that  tuberculosis  of  the  nodes  has  a  tendency  toward 
the  conservative  processes  of  sclerosis  and  limitation,  and  that  general 
dissemination  is  not  likely  to  occur;  exceptions  to  this  statement  are 
not  infrequent. 

'  See  Paths  of  Infection  in  Tuberculosis,  p.  148. 


I.V.M  I'll -NODES.  447 

The  histology  of  this  type  of  lymphadenoid  tuberculosis  is  usually 
quite  characteristic  and  permits  a  reasonably  accurate  diagnosis  even 
when  the  bacillus  cannot  be  demonstrated.  With  the  dei)Osit  of  the 
tubercle  bacilli  in  the  lymph-node  the  evidence  of  infection  begins. 
There  is  quicklv  developed  an  epithelioid  accumulation  resulting  from 
proliferation  of  the  endothelial  cells  of  the  lymph  paths;  to  these  are 
added  a  few  polvmorphonuclear  leukocytes,  which,  with  the  accumu- 
lation of  mononuclear  cells  apparently  of  hemal  origin,  constitute  the 
anatomicallv  mature  tubercle.  A  number  of  these  Ijecome  confluent, 
and  caseation  occurs,  followed  by  local  diffusion  involving  the  whole 
node  and  later  a  periadenitis  that  binds  the  nodes  of  the  area  together. 
The  infection  mav  spread  to  the  circumadenoid  tissues,  and  eventually, 
by  the  route  of  least  resistance,  may  reach  the  skin.  During  this  time 
it  is  possible  that  some  of  the  bacilli  may  have  passed  the  node  and 
assured  further  extension  of  the  process  by  a  second  incursion  through 
the  Ivmph-stream.     (See  Tuberculosis,  p.   153.) 

The  course  just  described  may  be  arrested  at  any  point.  The 
bactericidal  action  of  the  lymphoid  structures,  including  the  leuko- 
cytes, mav  terminate  the  process  by  a  victory  for  the  inhibiting  forces, 
tiie  bacilli  succumbing  or  becoming  so  surrounded  by  a  protective 
cordon  of  leukocytes  as  to  limit  the  lesion  to  the  area  involved,  or, 
possibly,  to  a  single  node,  or  even  to  a  part  of  a  node.  This  "  healing- 
in"  of  the  affected  tissues  does  not  represent  a  cure,  but  merely  a  quies- 
cent infection,  which  may,  when  the  protective  power  is  weakened  by 
some  secondarv  or  intercurrent  malady,  break  out  anew.  The  relation 
of  these  glands  to  the  production  of  miliary  tuberculosis  is  discussed 
on  page  154.  Caseous  nodes  may  discharge  into  serous  or  other  cavities: 
Metcalfe^  reports  an  instance  of  sudden  death  due  to  rupture  of  a  caseous 
node  into  the  trachea  just  above  the  bifurcation. 

Syphilitic  Lymphadenitis. — The  nearest  anatomic  lymph-node  drain- 
ing an  area  in  which  there  is  an  initial  lesion  of  syphilis  manifests, 
as  a  rule,  a  reaction  to  the  invasion,  which  is  quickly  followed  by  swelling 
of  contiguous  nodes,  and  eventually,  in  the  vast  majority  of  cases,  by 
hyperplasia  of  the  lymphadenoid  tissues  at  large.  This  initial  or  primary 
glandular  involvement  seems  to  be  almost  purely  a  proliferative  change 
in  the  cells  of  the  lymphoid  follicle  and  further  blocking  by  leukocytes. 
The  change  is  usually  transiton,',  and  disappears  in  a  few  days  under 
treatment,  and,  often,  in  a  few  weeks  without.  In  addition  to  this 
primarv  involvement  of  the  nodes  gummata  may  be  present  in  an  active 
stage  of  development,  or  gummatous  changes  represented  by  atrophied, 
cicatrized,  or  caseous  areas  of  a  practically  cured  tertiary  glandular 
lesion, 

Hodgkin's  disease,'  lymphadenia,  lymphadenoma,  lymphosarcoma, 
progressive    lymphadenoid    hyperplasia,    malignant    lymphoma,    simple 

'  "Lancet,"  Mav  2>,   i(»oi. 

*  Reed.  "Johns  Hopkins  Hospital  Reports,"  1902.  vol.  x,  p.  133.  Hitschmann 
and  Stross.  'Dettt.  med.  Woch.,"  May  21,  1903.  Simmons,  'lour,  of  Med.  Re- 
search," 1903.  Tuerck,  'Wien.  klin.  Woch.."  1903.  No.  39.  Longcope,  "Bulle- 
tin of  the  Aver  Clinical  Laboratory  of  the  Pennsylvania  Hospital,"  Oct.,  1903. 
Xo.  I.  Falkcnheim.  'Zeit.  f.  klin.  'Med.."  1904.  Iv.'  Gamasaki.  "Zeit.  f.  Heilk.," 
1904.  Bd.  x.xv.  Heft  7,  p.  269.  Hutchison,  "Lancet."  1904.  vol.  i.  Shaw, 
Practitioner,"  Oct.,  1904,  p.  517.  Wells  and  Maver,  "Amer.  Jour,  of  Med. 
Sci.,"  Nov.,  1904.  p.  837. 


44S 


SPECIAL  PATHOLOGY. 


adenia,  pseudoleukemia,  and  other  more  or  less  synonymous  terms, 
have  been  appHed  to  a  pecuHar  form  of  lymphoid  change  in  which  one 
or  more  of  the  lymphadenoid  tissues  of  the  body  are  involved,  including 
not  only  the  lymph-nodes,  the  spleen,  and  the  tonsils,  but  even  the 
Ivmphoid  tissues  of  the  various  mucosae.  There  can  be  no  doubt  that 
a  number  of  conditions  have  been  included  in  this  group,  but  careful 
study  by  modern  methods,  and  particularly  the  investigations  of  Reed, 
Simmons,  and  Longcope,  render  it  possible  to  recognize  a  fairly  definite 
anatomic  picture,  properly  to  be  identified  as  distinct  from  neoplasms 
affecting  the  lymph-nodes  and  not  due  to  any  form  of  infection  with 

which    we    are    at    present 
^_  familiar. 

The  glandular  enlarge- 
ment follows  no  law;  each 
case  differs  from  all  others. 
As  a  rule,  the  first  nodes 
to  enlarge  are  the  cervical. 
A  cluster  of  lymph-nodes 
may  become  prominent  in 
a  comparatively  short  time, 
may  remain  quiescent  some- 
times for  months,  and  then 
suddenly  take  on  renewed 
activity.  Following  the  cer- 
vical nodes  in  order  of  fre- 
cjuency  come  the  axillary 
and  inguinal  glands.  In  ex- 
tremely rare  cases  the  dis- 
ease begins  in,  and  remains 
restricted  to,  some  group 
of  internal  nodes,  such  as 
the  mediastinal,  retroperi- 
toneal, or  bronchial ;  later  in 
the  affection  usually  all 
these  groups  are  implicated 
Some  of  the  glands  may 
contain  caseous  areas  ac- 
curately circumscribed,  and 
probably  the  result  of  a  past, 
or  superimposed,  tubercu- 
lous infection.  The  disease, 
however,  bears  no  relation  to 
tuberculosis — association  of 
the  infection  is  mentioned 
onlv  to  indicate  the  possibility  of  combined  lesions.  The  process  is  not  re- 
stricted to  the  lymph-nodes  properly  so  called,  but  the  lymphoid  tissues 
throughout  the  body  may  manifest  a  certain  amount  of  involvement,  new 
areas  of  Ivmphadenoid  tissue  sometimes  develop.  The  splenic  changes 
have  already  been  considered.  (See  p.  439.)  The  adenoid  tissue  of  the  ali- 
mentary canal  becomes  conspicuous,  and  lymphoid  growths  in  the  liver 
and  pancreas  are  occasionally  found.  The  thymus  and  thyroid  bodies 
and  the  suprarenal  capsule  may  be  involved;  rarely,  lymphoid  growths 
occur  in  the  central  nervous  system. 


\ 


Fig.  231.— Hodgkin's  Disease. — {From  a  photograph  taken  a 
jew  weeks  before  the  death  oj  the  patient  from  mediastinal 
involvement.) 

The  lymphatic  enlargement  in  both  axilla:  is  shown,  as  well  as 
the  unusual  coUarTike  glandular  involvement  in  the  neck. 
The  nodes  of  the  left  axilla  show  the  tuberous  or  nodular 
character  of  the  enlargement,  as  they  have  not  as  yet  mat- 
ted together.  In  the  right  axilla  the  individual  nodes  are 
not  easily  outhned.  The  right  arm  is  swollen  from  pres- 
sure on  the  axillary  vein,  and  possibly  from  obstruction  to 
the  lymph  flow  through  the  involved  nodes.  At  postmor- 
tem exainination  the  mediastinal,  retroperitoneal,  mesen- 
teric, and  inguinal  lymphatics  were  all  found  to  be  in- 
volved.  (Patient  of  Professor  J.  C.  Wilson,  in  the  wards 
of  the  Jefferson  Medical  College  Hospital.) 


LYMPH-NODES.  449 

The  enlarged  nodes  are  white  or  .s^'rayish-white,  and  are  either 
fimi  or  soft,  depending  upon  the  rapidity  of  their  growth;  in  rare  cases 
there  may  be  evidence  of  necrosis  in  the  interior.  As  a  rule,  they 
remain  distinct  until  reciprocal  pressure  or  peripheral  growth  has  coal- 
esced them,  and  not  until  they  have  attained  considerable  size  do  thev 
show  evidence  of  marked  periadenoid  extension ;  to  this  rule  there  are 
notable  exceptions,  and  occasionally,  in  a  grouj)  of  glands,  many  dif- 
ferences in  consistency,  in  color,  and  in  evidences  of  infiltration  may 
be  present. 

Histologically  the  growths  from  different  cases  rarely  j)resent  iden- 
tical changes.  There  runs,  however,  through  them  all,  certain  con- 
spicuous alterations  by  which  it  is  possible  to  identify  the  condition. 
In  the  early  stages  the  lymphadenoid  hyperplasia  is  the  most  strik- 
ing feature;  later  endothelial  proliferation  becomes  marked  and  a 
notable  increase  in  the  fibrous  tissue  of  the  reticulum  develops.  In 
addition  to  the  conspicuous  increase  in  the  lymphoid  elements,  giant 
cells,  which  may  be  mononuclear  or  polynuclear,  appear  in  varying 
numbers.  Reed  is  of  the  opinion  that  these  elements  are  derived  from 
the  endothelial  cells  of  the  reticulum.  Freciuently,  but  not  invariablv, 
polymorphous  eosinophile  cells  are  abundant  throughout  the  growth.  In 
a  case  which  1  recently  examined  no  eosinophils  were  present  in  nodes 
removed  a  few  weeks  before  death,  but  the  specimens  obtained  at  autopsy 
contained  large  numbers  of  these  cells.  The  eosinophiles  of  the  marrow 
and  the  myelocytes  may  be  increased.  The  histology  of  the  enlarged 
spleen  and  of  the  secondary  growths  in  the  liver  and  elsewhere  is  essen- 
tially similar  to  that  of  the  involved  nodes. 

Tumors  of  Lymph-nodes. — If  we  except  the  foregoing  enlargements 
from  the  tumors  of  lymph-nodes,  the  only  important  primary  tumor 
of  these  structures  is  sarcoma:  the  alveolar,  round-cell,  melanotic,  and 
mixed-cell  forms  occur  in  the  order  given.  Sarcoma  may  be  secondary 
as  well  as  primary,  but  is  less  commonly  so.  The  frequent  secondary 
tumor  of  lymph-nodes  is  cancer.  In  all  its  forms  carcinoma  involves 
the  lymph-spaces;  the  extent  of  this  involvement  of  the  primitive 
lymph  paths,  and  the  portability  of  the  invading  cells,  together  with 
the  resistance  of  the  individual,  detennine  the  rapidity  with  which 
the  tumor  cells  reach  the  lymph-node  anatomically  nearest  to  the 
primary  growth.  Thus,  the  rapidly  growing,  almost  spheric,  cells 
of  the  encephaloid  spread  more  rapidly  than  the  squamous  or  flat 
irregular  cell  of  the  epithelioma.  (See  Tumors,  pp.  312  and  323.) 
When  cancer  involves  lymph-nodes,  the  histology  of  the  primary  tumor 
is  usually  as  fully  reproduced  as  the  gland  and  its  surrounding  struc- 
ture will  admit. 

Osteomata,  chondromata.  and  endothelioma  occasionally  involve 
lymph-nodes,  but  are  rare.  Lymphangiomatous  cysts  sometimes  occur 
in  the  l\-mph-nodes. 


30 


CHAPTER    IV. 
THYMUS    BODY.i 

In  the  last  months  of  intrauterine  Ufe  and  during  the  first  two 
years  of  infancy  the  thymus  body  may  be  justly  called  a  gland,  as 
it  contains  epithelial  elements  arranged  in  lobes,  with  subdivision  into 
lobules,  and  a  minute  structure  resembling  that  of  certain  glands. 
Even  before  birth  displacement  of  the  epithelial  structures  by  lymphoid 
tissues  is  marked,  and  this  substitution  persists  to  the  second,  third, 
or  fourth  year.  After  this  time  atrophy  progresses,  and  by  the  tenth 
vear  the  adenoid  structure  has  been  replaced  by  fat  and  fibrous  tissue, 
and  at  puberty,  or  shortly  afterward,  the  gland  can  rarely  be  identified, 
or  at  most  but  a  small  vestige  may  be  found. 

Malposition  and  Malformation. — The  organ  may  be  absent,  and 
there  may  be  no  evidence  of  its  ever  having  developed.  In  other  in- 
stances even  in  infancy  it  may  be  scarcely  demonstrable.  Accessory 
lobes,  and  even  fully  formed  accessory  glands,  are  occasionally  observed. 
Rarely,  the  gland  may  be  out  of  place,  approaching  the  thyroid,  or, 
less  commonly,  anterior  to  the  heart  and  below  its  normal  position;  in 
some  instances  a  lateral  displacement  may  be  present,  and  still  less 
frequently  the  thymus  vestige  may  be  found  in  the  peribronchial  con- 
nective tissues.  Persistence  of  the  gland,  either  with  or  without  enlarge- 
ment, is  occasionally  obser\'ed.  In  the  absence  of  any  distinct  over- 
growth it  may  be  questioned  whether  any  symptoms  or  lesions  result. 

Atrophy  of  the  thymus,  as  previously  stated,  is  a  normal  process. 
Dudgeon  divides  the  atrophies  into  primar}'  and  secondary;  in  the 
former  the  gland  may  weigh  less  than  a  gram,  the  lymphoid  tissue  is 
wasted,  poly  nuclear  giant  cells  are  usually  present,  and  many  of  Has- 
sall's  corpuscles  are  calcified.  Hemorrhages  are  sometimes  present 
and  fatty  infiltration  is  often  conspicuous.  Ruhrah  makes  this  change 
the  anatomic  basis  of  marasmus.  Secondary  atrophy  of  the  gland 
is  seen  in  wasting  diseases  of  all  kinds,  particularly  tuberculosis.  In 
the  secondary  atrophy,  fibrosis  is  the  most  conspicuous  change.  Hyper- 
plasia of  the  fibrous  tissue,  with  increase  in  the  lymphoid  structure, 
giving  rise  to  considerable  glandular  enlargement,  sometimes  called 
thymic  hypertrophy,  is  occasionally  seen.  Normally,  the  thymus  gland 
varies  in  weight  between  5  and  10  gm.  at  the  stage  of  its  fullest  de- 
velopment. The  enlarged  thymus  may  weigh  from  20  to  100  gm.,  and 
may  retain  a  weight  of  from  20  to  25  gm.  in  the  adult.  Very  often 
this  persistence  or  enlargement  of  the  th^^mus  is  present  without  any 

^  The  literature  concerning  the  thymus  gland  is  quite  voluminous.  For  recent 
studies  of  the  physiolog\'  of  the  organ  see  Paton  and  Goodall,  "Jour,  of  Physi- 
ology," 1904,  vol.  xxxi,  No.  I.  Cecca  and  Zappi,  "  Bulle.  del  Sci.  Med.,"  March, 
1904.  Paton,  "Jour,  of  Physiol.,"  Dec.  30,  1904.  Sinnhuber,  "Zeit.  f.  klin. 
Med./'  1905,  vol.  54,  Nos.  i  and  2.  For  recent  studies  on  the  pathologj'  of  the 
gland  consult  Dudgeon,  "Jour,  of  Path,  and  Bact.,"  1904-1905,  vol.  x,  p.  473; 
bibliography. 

450 


TIIVMI'S    HoDY.  45  I 

associatoU  phenoiiu-na.  In  otlicr  instances  it  is  ()l)serve(i  in  connection 
with  goiter  and  with  the  lyniijhoid  and  adenoid  enhirj,'ements  of  leu- 
kemia and  Hodi,'kin's  lUseasc.  Herard,  Bontenips,  (irawitz,  Marfan, 
Brouardel,  and  others  beUeve  that  enhirj^^ement  of  the  thymus  is  in- 
lluential  in  the  production  of  sudden  death,  ijarticularly  in  children — 
so-called  thymic  death.  Following  thymic  death,  as  well  as  asphyxia 
from  other  causes,  iwhyniosis  and  marked  congestion  are  commonly 
found  in  the  thvmus.  Pctcchicc  and  ecchynioses,  or  even  larger  hcmor- 
rhaiiic  iiifiltriitious,  are  also  occasionally  observed  in  the  gland  in  scurvy 
and  in  acute  infections  occurring  during  infancy. 

Lymphatism,  status  lymphaticus,  and  lymphatic  constitution  an- 
names  applied  to  a  contlitmn  m  which  there  is  general  hyiicrplasia  nt 
many  lymphoid  tissues,  including  the  thymus  gland.  The  s]jleen  is 
usuallv  enlarged,  Peyer's  patches  are  prominent,  and  sudden  death 
is  not  uncommon.  These  patients  bear  anesthesia  badly,  and  sudden 
death  has  occurred  during  minor  operations  under  local  anesthetics. 
The  condition  may  be  associated  with  rickets.  Ohlmacher  has  noted 
the  coincidence  of  status  lymphaticus  and  epilepsy.  Sudden  death 
in  these  cases  has  been  attributed  to  pressure  on  the  trachea,  heart,  or 
great  vessels,  and  to  the  action  of  toxic  substances  present  in  the  blood. 

Little  is  known  of  inflammations,  degenerations,  and  necroses  that 
occur  in  the  thvmus.  That  the  body  is  subject  to  embolism  is  indicated 
bv  the  occurrence  of  abscesses  in  pyemia,  and  sometimes  in  septicemia. 

In  common  with  other  tissues  it  is  liable  to  invasion  by  miliary 
tul;)ercles,  and  occasionally  contains  the  caseous,  fibrocaseous,  or  cre- 
taceous nodules  of  chronic  tuberculous  infection.  Gummata  of  the 
thymus  have  been  observed. 

Primarv  tumors  of  the  thymus  gland  are  rare.  By  reason  of  the 
presence  of  epithelium,  carcinoma  is  probably  the  most  frequent 
tumor;  however,  sarcoma  of  the  round-cell  type  is  relatively  frequent. 
Lvmphoid  proliferation  occurs  in  Hodgkin's  disease  and  in  leukemia. 


CHAPTER  V. 
SEROUS   MEMBRANES. 

The  normal  serous  membrane  is  composed  of  a  flattened  layer  of 
connective-tissue  cells  (endothelium)  resting  upon  a  subserous  network 
of  loose  connective  tissue  in  which  ramify  the  blood-vessels,  lymphatics, 
and  nerves.  The  membrane  is  lubricated  by  a  serous  fluid,  about  the 
origin  of  which  there  has  been  considerable  discussion.  The  older  view, 
that  it  is  a  transudate,  must  be  modified.  The  statement  that  the  fluid 
normallv  present  in  the  serous  cavities  is  a  transudate  rather  than  a 
secretion  is  based  upon  the  view  that  lymph  is  not  a  secretion;  this 
matter  has  been  already  discussed,  and  need  not  be  reviewed;  the 
reader  is  referred  to  the  article  on  Edema,  page  267.  An  important 
histologic  and  physiologic  fact,"  of  great  practical  significance,  is  the 
demonstration  that  the  serous  cavity  is  in  direct  communication  with 
the  lymph-spaces  of  the  subserosa  and,  in  some  instances,  with  the 
lymph-paths  of  the  organs  and  structures  covered.  The  exact  char- 
acter of  this  communication  is  still  a  subject  of  controversy;  the  older 
view  that  the  lymphatics  adjacent  to  the  serous  membranes  communi- 
cated with  the  cavity  by  open-mouthed  vessels  (stomata)  has  been 
attacked  and  somewhat  modified,  but  the  communication  has  not  been 
disproved.  If  India  ink  be  injected  into  the  subserosa,  the  granules 
appear  in  the  serous  cavities;  and  if  this  substance,  or  other  material 
containing  finely  divided  particles,  be  injected  into  the  peritoneum, 
the  granules  may  be  traced  in  the  diaphragm  and  are  sometimes  found 
in  the  lymph-nodes  that  drain  the  area.  .The  importance  of  this  demon- 
stration can  not  be  overestimated,  as  it  explains  the  occurrence  of  in- 
flammation of  the  serous  membranes  covering  affected  viscera,  makes 
it  evident  why  pleurisy  frequently  accompanies  pneumonia  (epipneu- 
monic  pleurisy),  why  inflammation  of  the  pleura  may  precede  or  follow 
inflammation  of  the  peritoneum,  and  also  renders  it  possible  to  under- 
stand the  changes  occurring  in  the  viscera  as  a  result  of  infection  of 
the  overlving  serosa.  The  blood-vessels  supplying  nourishment  to  the 
serous  membrane  constitute  a  fine  capillary  network  distributed  in  the 
subserosa;  the  thin  endothelial  investment  readily  permits  the  absorp- 
tion of  toxic  substances  from  a  serous  cavity  and  offers  little  resistance 
to  the  passage  of  infectious  material  from  the  underlying  capillaries 
to  the  serous  surface. 

The  serous  cavities  of  the  body  are  the  peritoneum,  the  pleurce,  the 
pericardium,  the  serous  covering  of  the  brain  and  cord,  the  synovial  struc- 
tures of  the  joints  and  tendon-sheaths,  and  the  lining  membranes  of  the 
htirscE.  When  one  of  these  membranes  is  examined  in  its  normal  con- 
dition, the  surface  is  found  to  be  moist,  smooth  and  shining,  and  the 
membrane  thin  and  transparent.  The  color  is  uniform  with  that  of 
the  tissue  which  it  covers,  and  where  two  layers  of  the  serous  membrane 
have  nothing  between  them  but  the  fibrous  or  fibro-elastic  network  on 

452 


SEROUS   MKMHUANES.  45.5 

whicli  they  rest,  it  may  he  practically  true  that  the  meml<rane  is  color- 
less. The  normal  serum  of  the  cavity  is  a  clear  fluid,  usually  of  a  lij^ht 
straw-color;  it  may,  however,  be  stained  by  osmosed  coloring-matter, 
as  the  coloring-matter  of  the  blood,  which  may  pass  through  the  heart 
postmortem  and  tinge  the  pericardial  fluid. 

The  quantity  of  fluid  j^resent  in  any  given  serous  membrane  is  de- 
pendent upon  the  amount  in  the  connective  tissues  elsewhere,  as  well 
as  the  surface  area  of  the  membrane  in  question,  and  must,  therefore, 
vary  in  quantity.  If  the  patient  has  died  slowly,  and  a  general  lym{)h 
stasis  has  ensued  from  the  gradual  slowing  of  the  circulation,  more  lluid 
will  be  found  in  the  serous  sacs  than  under  conditions  of  rapid  death. 
The  amount  of  fluid  that  can  be  collected  will  approximate,  in  the  peri- 
toneum, from  8  to  50  c.c. ;  in  the  pleura,  from  30  to  100  c.c. ;  in  the  peri- 
cardium, from  4  to  30  c  c. 

If  during  life,  for  any  reason,  there  is  slowing  of  the  circulation 
leaving  a  serous  membrane  or  the  organ  which  it  incloses,  there 
is  a  disposition  for  fluid  to  accumulate  in  the  serous  cavity,  just 
as  obstruction  to  the  onward  flow  of  blood  in  any  part  of-  the  body 
leads  to  the  infiltration  of  the  lymph-spaces  with  serum.  Such  an  accu- 
mulation constitutes  what  is  often  spoken  of  as  dropsy  of  a  serous 
cavity.  Ascites,  or  hydropcritonciim ,  from  obstructive  lesions  in  the  liver 
is  an  example  of  this  condition.  The  accumulation  of  fluid  in  the  pleura 
{hydrothorax)  in  pulmonary  edema  and  general  dropsy  is  a  second  in- 
stance; similar  conditions  may  cause  hydro  pericardium .  Steele^  and 
also  Stengel  have  shown  that  in  the  hydrothorax  of  heart  disease  the 
effusion  is  sometimes  unilateral,  in  which  case  it  is  commonly  restricted 
to  the  right  side,  and  when  bilateral  the  larger  quantity  of  fluid  is  usually 
in  the  right  pleura.  It  is  thought  that  this  difference  in  the  two  sides 
may  depend  upon  pressure  of  the  enlarged  right  heart  on  the  root  of  the 
right  lung  and  the  vena  azygos  major;  it  is  also  to  be  remembered  that 
the  serous  surface  of  the  right  pleura  is  the  larger,  and  that  any  condition 
tending  to  increase  the  output  of  fluid  from  the  serosa  would  be  likely 
to  give  rise  to  a  larger  quantity  upon  the  right  side.  With  enlargement 
of  the  left  heart  there  is  usually  a  tendency  toward  a  left-sided  effusion 
or  at  least  a  larger  fjuantity  of  fluid  in  the  left  pleura.  The  accumulated 
fluids  interfere  mechanically  with  the  function  of  the  organs  in  the 
affected  cavity,  and  increase  the  venous  congestion,  which  may  have 
been  the  original  cause. 

Accumulations  of  serum,  without  any  gross  evidence  of  inflamma- 
tion, occasionally  occur  in  serous  cavities  where  the  membrane  is  infil- 
trated by  miliar)'  tubercles.  The  tubercles  surrounding  and  obstructing 
the  small  vessels — arteriole,  capillary,  and  vein — lead  to  extravasation 
exactly  as  would  any  other  obstructive  lesion;  it  is  also  probable  that  the 
irritation  produced  by  the  tubercle  bacillus  or  its  poisons  increases  the 
permeability  of  the  endothelium  or  induces  an  inflammation  of  such  a 
low  order  that  the  resulting  fluid  possesses  more  of  the  characters  of  a 
transudate  than  of  an  exudate.  The  process  is  most  frequent  in  the 
peritoneum,  where  not  uncommonly  gallons  of  fluid  may  be,  at  different 
times,  drawn  off.  only  to  reaccumulate,  as  in  the  ascites  due  to  obstruc- 
tion of  the  portal  vein  radicles  in  the  liver. 

In  addition  to  the  dropsical  conditions  arising  from  chronic  diseases 
'  "Jour.  Amer.  Med.  Assoc.,"  Oct.  i,  1964;    bibliography. 


454 


SPECIAL  PATHOLOGY. 


of  the  heart  and  of  the  kidneys,  and  the  local  obstruction  to  the  circula- 
tion secondary  to  cirrhosis  or  protracted  congestion  of  the  liver,  chronic 
or  persistent  irritation  of  any  kind  affecting  a  serous  membrane  is  likely 
to  induce  more  or  less  serous  accumulation  within  its  cavity.  Such  per- 
sistent irritation  is  occasionally  observed  in  the  joints,  giving  rise  to 
hydrops  arthrosis,  sometimes  called  joint  dropsy. 

The  fluid  present  in  dropsical  conditions  of  serous  membranes  differs 
materially  in  composition  from  the  inflammatory  exudates.     Its  specific 
gravity  is  usually  low — loi 5  or  lower.     As  a  rule,  it  is  clear;  occasionally, 
however,  it  may  be  cloudy.     Cloudiness  is  more  frequent  in  hydroperi- 
toneum  than  in  dropsies  o'f  other  serous  cavities.     When  the  accumula- 
tion is  due  to  obstruction  of  the  lacteals,  as  it  may  be  in  the  peritoneum, 
the  milky  opacity  is  to  be  attributed  to  the  presence  of  fat  globules. 
These  are  usually  easily  recognized  under  the  microscope,  and  may  be 
further  identified  by  the  usual  tests  for  fat.     (See  p.  244.)     It  has  been 
the  custom  to  assume  that  the  abundant  presence  of  leukocytes  arose 
only  in  connection  with  inflammation,  but  Poljakoff^  has  reported  a  case 
in  which  the  milkiness  of  the  transudate  was  apparently  due  entirely 
to  the  presence  of  white  blood-cells.     In  Poljakoff's  case  the  low  specific 
gravity  (1009)  favored  the  exclusion  of  inflammation.     In  true  milky 
ascites'  the  fluid,  on  standing,  usually  evinces  partial  separation  into 
three  layers:  the  uppermost  layer  is  milky  or  cream -like,  and  contains 
fat;  the' sediment  is  composed  of  leukocytes  and  cellular  detrittis,  while 
the' intervening  layer  may  be  quite  clear.     True  chylous  ascites^  results 
from  the  escape  of  chyle  into  the  peritoneal  cavity  and  may  be  due  to 
obstruction  of  the  thoracic  duct,  disease  of  the  receptaculum  or  lacteals, 
and  to  the  rupture  of  chylous  vessels  or  cysts  in  the  mesentery.     In  the 
thorax  the  condition  results  from  injuries  and  rarely  from  neoplastic  or 
tuberculous  invasion  of  the  thoracic  duct.     True  chylous  fluids  contain 
sugar,  and  the  melting-point  of  the  fat  approximates  that  of  the  fats 
ingested.      The  accumulations  are  usually  rapid    and,   after    removal, 
quickly  reform.     Those  fluids  in  which  the  resemblance  to  chylous  liquids 
is  striking,  but  in  which  the  opacity  is  not  due  to  fat  derived  from  the 
chyle,  are  called  chyliform.     Chyliform  ascites  is  the  commonest  of  these 
accurnulations.     Chyliform  fluids  accumulate  slowly,  are  usually  rela- 
tively rich  in  cells,  are  not  infrequently  associated  with  neoplastic  in- 
volvement of  the  serosa,  commonly  contain  no  sugar,  and  the  fat  con- 
tent is  not  influenced  by  the  quantity  or  character  of  the  ingested  fats. 
Chemic  examination  shows  that  the  amount  of  fat  is  small,  rarely  attain- 
ing 0.15  per  cent.      In  true  chylous  ascites  the  quantity  of  fat  varies  be- 
tween one  and  three  per  cent.,  and  sometimes  is  much  more.     Pagen- 
stecher  beheves   that   chyliform   fluids   are   produced  by   degenerative 
changes  in  the  contained  cells  resulting  in  the  production  of  molecular 
fat;  such  transformation  may  explain  some  cases,  but  it  is  probable  that 
in  most  instances  the  cloudiness  is  due  to  a  proteid  resembling  that  which 
causes  the  opacity  of  fat-free  milk. 

The  order  in  which  the  serous  cavities  of  the  body  are  examined 
is:  (i)  Peritoneum;  (2)  pleura;  (3)  pericardium;  and'  (4)  the  serous 
membranes  covering  the  brain  and  cord.     The  processes  in  each  of  these, 

1  "Berliner  klin.  Woch.,"  1900,  No.  i,  p.  9. 

^  The  subject  of  chylous  and  chyliform  ascites  is  fully  reviewed  by  Boston, 
"Jour.  Amer.  Med.  Assoc,"  Feb.  18,  1905,  p.  513;    bibliography. 


SEROUS   MI'MMK.WlvS.  455 

wlicn  affected  by  disease,  vary  su  little  the  variation  dependinj,'  not  so 
much  upon  tiie  membrane  as  upon  the  surroun<linj^  structures — that 
it  is  possible  to  study  in  detail  disease  aflfectinj^f  one  of  the  cavities  and 
apply  the  knowledi^^e  thus  ac(|uired  to  any  or  all  of  the  other  serous  mem- 
branes with  but  sli*,dit  modification:  c.  (j.,  tlie  brain,  being  inclosed  in  a 
rigid  covering  (the  skull),  is  never  surrounded  by  large  accumulations 
of  fluid  so  constantly  found  in  inflammations  of  the  jjleura. 

Malpositions  of  the  various  serous  membranes  are  determined  l)y 
ectopia  of  the  viscera  contained  in  the  cavity,  and,  in  the  absence  of  such 
conditions,  are  rarely  observed.  Malposition  of  the  heart  leads  to  dis- 
placements of  the  pericardium;  in  hernias  or  other  mali)Ositions  of  the 
abdominal  viscera  or  lungs  the  serosa  accompanies  the  ectopic  viscus. 
The  same  general  statement  ajijilies  to  malformation  of  other  serous  mem- 
branes; the  surface  distribution  of  the  seros;^  is  determined  by  the  con- 
tour of  the  enclosed  organs  and  the  shape  of  the  parietes  which  the  ser- 
ous membrane  lines;  when  these  structures  are  normal,  developmental 
defect  in  the  enveloping  serosa  is  exceedingly  rare. 

Malformation  of  the  pericardium  occurs  T)ut  rarely,  and  usually  con- 
sists of  partial  or  loniplctc  absoifc  of  the  membrane.  One  should  not  l)e 
misled  bv  considering  universally  adherent  pericardium  as  illustrative  of 
absence  of  the  organ.  Normally,  the  phrenic  nerves  are  widely  separated 
bv  the  pericardium,  but  in  those  cases  of  absence  of  the  pericardium 
that  have  been  reported  the  two  nerves  are  almost  side  by  side.  This 
will,  therefore,  aid  in  demonstrating  that  the  pericardium  was  present 
at  one  time,  and  that  inflammation  sealed  its  walls  together.  Evi- 
dences of  past  inflammation  are  usually  to  be  found.  Adhesions  to  the 
surrounding  structures,  thickening  of  the  adjacent  pleura,  and  sometimes 
induration  of  the  mediastinal  tissues  will  offer  further  aid  in  recognizing 
the  essential  character  of  the  process.  Sometimes  adventitial  folds 
and  duplications  may  be  found  near  the  base  of  the  heart,  great  vessels, 
or  along  the  margins  of  the  auricles.  Rohn'  records  four  instances  in 
each  of  which  a  pericardial  diverticulum  was  present;  usually  such  a  sac 
or  pouch  projects  into  the  mediastinal  tissues  and  toward  the  right  side. 
Occasionally  fenestra  between  the  pleura  or  peritoneum,  and  pericardial 
cavity,  are  observed. 

Maculae  albidae,  toidinoiis  patches,  or  white  or  milk  spots  on  the  peri- 
cardium, are  occasionally  found,  and  are  usually  due  to  the  heart  thump- 
ing, at  each  pulsation,  against  some  hard  body,  such  as  a  prominent 
costal  cartilage,  or,  more  rarely,  the  vertel)ra'.  These  spots  are  to  be 
differentiated  from  the  deeper  lesions  of  fibroid  change  in  the  cardiac 
muscle  by  the  former  being  thin,  sujierflcial.  and  not  in  the  muscle,  but 
on  its  surface.  It  is  generally  admitted  that  the  so-called  milk  sj)Ots 
do  not  have  their  origin  in  any  acute  inflammatory  condition.  Each 
spot  is  essentially  a  localized  fibrosis,  commonly  restricted  to  the  peri- 
cardium and  subpericardial  tissue,  and  rarely  involving  the  myocar- 
dium. When  the  fibrosis  extends  into  the  muscle,  it  is  usually  only  a 
verv  superficial  invasion,  although,  in  rare  cases,  local  extension  of  the 
newly  formed  fibrous  tissue  into  the  cardiac  wall  may  be  observed.  In 
such  instances  it  is  quite  impossible  to  say  that  the  condition  did  not 
first  involve  the  muscle — an  interstitial  myocardial  fibrosis.  The  spots 
are  pure  white,  grayish-white,  or  even  pearly  in  color;  rarely,  of  a  ])inkish 
*  "Wien.  klin.  Woch.,"  iqo;?,  Wi.   rx. 


456  SPECIAL  PATHOLOGY. 

hue.  Occasionally,  a  spot  may  be  slightly  calcareous.  They  are  usually 
situated  in  the  visceral  pericardium  near  the  base  or  anterior  surface  of 
the  right  ventricle  or  near  the  apex  of  the  left.  Milk  spots  are  infrequent 
in  childhood,  and  are  more  often  present  with  advancing  years.  They 
are  more  frequent  in  males  than  in  females.  Enlarged  hearts  are  more 
commonly  affected;  particularly  is  this  the  case  in  hypertrophy. 
Structures  possessing  the  same  general  characters  and  histology  are  some- 
times found  on  other  viscera.  The  spleen  is  often  affected,  and  the 
liver  less  frequently.  The  condition  is  a  local  fibrous  hyperplasia  due 
to  repeated  slight  injuries  or  other  form  of  circumscribed  irritation. 

Infiltrations. — Pigment  is  rarely  found  in  the  pericardium.  Fatty 
infiltration  is  occasionally  observed.  Calcareous  areas  may  be  seen, 
particularly  if  the  membrane  has  ever  been  the  seat  of  inflammation. 
Ernst  Jones  ^  collected  58  cases  of  calcified  pericardium.  The  con- 
dition is  twice  as  common  in  the  male  as  in  the  female.  In  most  of  the 
cases  there  were  no  clinical  signs  indicative  of  the  condition.  The 
process  is  essentially  chronic,  persisting  for  fifteen  or  twenty  years. 
In  thirteen  per  cent,  of  the  collected  cases  there  was  a  probability  that  the 
condition  was  secondary  to  suppurative  pericarditis.  Sometimes  in 
fibrous  areas  resulting  from  past  pericardial  inflammation  extensive 
calcareous  infiltration  is  found.  At  times  this  calcific  deposit  may  be 
so  great  that  one  can  but  wonder  how  the  heart  has  maintained  its  con- 
tractile power;  the  whole  of  the  pericardium  may  show  more  or  less 
calcareous  infiltration,  and  at  points  the  calcific  layer  may  be  five  mil- 
limeters in  thickness.  Such  extensive  calcareous  infiltration  is  usually 
to  be  regarded  as  evidence  of  past  inflammation,  and  it  is  doubtful 
whether  calcification  occurs  in  a  serous  membrane  that  has  not  been  the 
seat  of  some  inflammatory  lesion. 

Degenerations. — Fatty,  myxomatous,  hyaline,  and  granular  changes 
occur,  but  not  frequently. 

Inflammation  of  the  pericardium  (pericarditis)  is  analogous  to  in- 
flammation of  the  peritoneum  (peritonitis),  inflammation  of  the  pleura 
(pleuritis,  or  pleurisy),  inflammation  of  the  meninges  (meningitis),  in- 
flammation of  the  synovial  membranes  (synovitis),  inflammation  of  the 
bursae  (bursitis),  inflammation  of  the  tendon-sheaths  (thecitis).  The 
term  serositis  is  used  to  include  any  serous  membrane  inflammation. 
When  a  number  of  serosse  are  simultaneously  or  sequentially  affected 
the  names  polyserositis,  multiple  serositis,  and  polyorrhomenitis  may  be 
emploved. 

Inflammations  of  the  serous  membranes  may  be  primary  or  sec- 
ondary. The  primary  inflammations  are  sometimes  called  idiopathic, 
based  upon  the  impossibility  of  definitely  ascertaining  the  essential 
etiologic  factor.  Nearly  all  the  inflammatory  conditions  aft'ecting  the 
serous  membranes  are  secondary  in  point  of  origin,  and  therefore  are 
practically  always  associated  with  some  other  morbid  process.  One  of 
the  most  frequent  causes  of  inflammation  of  the  serous  surfaces  is  ex- 
tension of  an  inflammatory  process  from  adjacent  structures.  Of  the 
many  examples  that  might  be  given  for  this  condition,  the  following 
should  be  mentioned:  Meningitis  secondary  to  disease  of  the  ethmoid, 
sphenoid,  and  mastoid  sinuses,  and  from  diseases  of  the  middle  ear  or 
cranial  bones;  pericarditis  secondary  to  pleurisy  or  mediastinitis,  ulcer- 
'  "Path.  Soc.  of  London,"  May  21,  1901. 


SEROUS   MlvMBRANES.  457 

ative  lesions  in  the  esophagus  or  stomach,  and  ])ericar(iial  intlammation 
due  to  infectious  processes  involvin<^  the  myocardium;  pleurisy  secon- 
dary to  diseases  of  the  underlying  pulmonary  tissue;  ])eritonitis  resulting 
from  perforation  of  the  intestine  as  well  as  from  suppurative,  perfo- 
rative, or  gangrenous  processes  in  the  appendix  or  intestine;  and  ex- 
tension of  infection  from  the  pelvic  viscera,  particularly  in  the  female. 
The  circuitous  route  usually  taken  by  suppurative  and  ulcerative  proc- 
esses occurring  in  organs  adjacent  to  the  diaphragm  may  lead  to  un- 
usual, or  even  extraordinary,  combinations  of  pathologic  conditions. 
Thus,  hepatic  abscess  may  induce  j^eritonitis  or  pleurisy,  or  both,  de- 
pending upon  whether  its  extension  is  directed  toward  the  diaphragm, 
through  which  it  may  jjerforate.  extending  even  into  the  lung  and  dis- 
charging its  contents  through  a  bronchus.  Gastric  ulcer  and  carcinoma 
of  the  stomach  may  perforate  the  peritoneum,  pleura,  or  pericardium. 

Inflammations  of  the  serous  membranes  may  also  arise  as  a  result  of 
specific  agents  circulating  in  the  blood.  In  pyemia  and  septicemia  in- 
flammations involving  the  joints,  pericardium,  pleura,  meninges,  and 
peritoneum  are  not  uncommon.  Inflammations  of  serous  membranes 
are  sometimes  said  to  be  cJicniic  or  aseptic,  in  contradistinction  to  inflam- 
matory conditions  arising  from  demonstrable  infection.  Thus,  it  has 
been  held  that  the  inflammation  of  the  joints  and  of  the  pericardium  in 
rheumatism,  for  example,  was  due  to  the  presence  in  the  circulating 
blood  of  irritants  probably  the  result  of  faulty  metabolism.  About  fifty 
per  cent,  of  the  cases  of  pericarditis  are  of  rheumatic  origin.  The  trend 
of  opinion  at  present  seems  to  be  toward  the  belief  that  rheumatism  is 
a  bacterial  disease  (see  Diplococcus  rheumaticus,  p.  112),  and  if  such 
origin  can  be  satisfactorily  demonstrated,  its  time-honored  use  as  an 
example  of  a  nonbacterial  cause  of  inflammation  of  serous  membranes 
can  not  be  justified,  and  the  possibility  of  distinctly  chemic  or  aseptic 
serous  inflammation  must  appear  less  admissible. 

Trauma  must  be  admitted  as  a  cause  of  inflammation  of  the  serous 
membranes;  meningitis  may  follow  cranial  or  spinal  injuries;  pleurisy 
or  pericarditis^  may  be  produced  l>y  penetrating  wounds,  contusions,  and 
crushes  of  the  thoracic  wall;  peritonitis  may  follow  abdominal  trauma, 
and  synovitis  and  bursitis  are  frequently  of  traumatic  origin.  That  the 
inflammation  is  the  direct  consequence  of  the  injury  seems  in  most  cases 
to  be  doubtful ;  the  frequency  with  which  surgeons  attack  the  serous 
membranes  clearly  shows  that,  in  the  absence  of  infection,  these  struc- 
tures tolerate  considerable  violence.  Schachner  has  collected  150 
recorded  instances  in  which  foreign  bodies  have  been  accidentally  left  in 
the  abdominal  cavity;  if  aseptic,  and  nonirritating,  encapsulation  and 
enclosure  by  adhesions  result-.  The  danger  from  trauma  is  largely  due 
to  the  fact  that  the  injured  membrane  is  frequently  infected,  or  its  re- 
sistance to  infection  so  lowered  that  it  may  readily  l)e  attacked  by  bac- 
teria. Injuries  that  destroy  tissue  or  permit  blood  to  accumulate  in  the 
serous  cavities  invite  infection;  therein  lies  the  greatest  danger.  The 
reparative  effort  necessary  for  healing  aseptic  wounds  of  the  serosa 
scarcely  rises  to  the  dignity  of  an  inflammation;  at  most,  it  produces 
nothing  more  than  a  slight  plastic  exudate  terminating  in  the  formation 
of  fibrous  tissue. 

•  Pleasants,  "Bull,  of  Johns  Hopkins  Hospital."  1903.  vol.  xiv,  p.  124. 

*  "Annals  of  Surgery."  November,  1901. 


458  SPECIAL  PATHOLOGY. 

Aneurysm  of  the  heart  or  of  the  aorta — the  latter  presenting  in  the 
pericardial  cavity — may  be  attended  by  pericarditis.  Allbutt^  recog- 
nizes a  dry  plastic  pericarditis  due  to  aortitis  and  usually  involving  the 
pericardium  contiguous  to  the  affected  aorta.  Malignant  growths  and 
chronic  infectious  processes  attacking  the  serous  membranes  usually  in- 
duce inflammation.  Embolism  involving  the  viscera  covered  by  serosa 
may,  if  the  infarct  reach  the  surface  of  the  organ,  give  rise  to  a  serositis, 
the'  character  of  which  must  depend  upon  the  nature  of  the  emboHc 
process.  Miller-  holds  that  many  cases  of  postoperative  pleurisy  are  of 
embolic  origin. 

Inflammation  of  the  serous  membranes  may  occur  in  the  course  of 
many  infectious  diseases.  In  a  number  of  these  it  is  due  to  the  specific 
organism  of  the  affection  which  it  complicates.  Thus,  in  croupous 
pneumonia,  pleurisy  is  practically  always  present,  the  pericardium  fre- 
quently affected,  and  peritonitis',  meningitis,  and  synovitis  sometimes 
result  from  the  pneumococcemia.  Keen^  collected  9  cases  of  pleurisy, 
2  cases  of  pericarditis,  15  of  meningitis,  and  98  of  arthritis  complicating 
typhoid  fever.  In  many  of  these  cases  the  typhoid  bacillus  was  ob- 
tained, sometimes  in  pure  culture.  Other  cases  of  serous  membrane 
inflammation,  due  to  the  typhoid  bacillus,  have  been  reported  by  Widal 
and  Lemierre,^  Kiche],=^  Gourand,*^  Gordinier,^  Cole^  and  others.  Sears'* 
states  that  Betke  observed  58  cases  of  pleurisy  in  1420  instances  of 
tvphoid.  In  influenza,  pleurisy  is  sometimes  observed,  peritonitis  has 
been  known  to  occur,  joint  complications  are  not  altogether  rare,  and 
meningitis  due  to  the  Bacillus  influenzae  is  occasionally  seen;  accord- 
ing to  Mya/"  there  are  17  recorded  instances  of  grippal  cerebrospinal 
meningitis.  The  serositis  sometimes  complicating  erysipelas  is  due 
to  the  hematogenous  dissemination  of  the  streptococcus.  In  a  number 
of  infectious  diseases  serous  membrane  inflammations  due  to  associated 
or  intercurrent  infections  are  sometimes  observed.  With  this  group 
of  cases  should  be  included  the  inflammations  of  the  serosae  occurring 
in  scarlet  fever,  smallpox,  measles,  and  allied  acute  infectious  diseases, 
concerning  the  specific  cause  of  which  additional  information  is  needed. 

In  the  chronic  forms  of  nephritis,  particularly  in  contracted  kidney, 
pericarditis  and,  although  less  commonly,  pleurisy  are  not  infrequent. 
These  affections  are  also  seen  in  gout  and  diabetes.  At  one  time  it 
was  maintained  that,  in  the  diseases  mentioned,  toxic  substances  cir- 
culating in  the  blood  were  responsible  for  the  complicating  inflamma- 
tion; it  is  now  generally  held  that  the  serositis  is  bacterial  in  origin 
and  that  the  diseases  with  which  it  occurs  favor  the  action  of  micro- 
organisms by  lessening  tissue  resistance  and  facilitating  the  dissemi- 
nation and  colonization  of  germs  which  enter  the  circulation.  In  many 
of  these  cases  the  complication  is  a  terminal  infection. 

'  "Lancet,"  July  18,  1903,  p.  143. 

^  "Amer.  Med.,"  Aug.  2,  1902. 

2  "Surgical  Complications  and  Sequels  of  Typhoid  Fever,"  1898. 

*  "C.  R.  Soc.  de  Biol.,"  1903,  vol.  Iv,  p.  1431. 
5  "Gaz.  des  Hop.,"  August  30,  1901. 

*  "Gaz.  des  Hop.,"  1903,  Ixxvi,  p.  375. 

'  "Amer.  Jour,  of  Med.  Sci.,"  Jan.,  1901. 

*  "Johns  Hopkins  Hospital  Bull.,"  Feb.,  1904,  p.  62. 

»  "Med.  and  Surg.  Reports  of  Boston  City  Hospital,"  1902,  13th  series,  p.  22. 
""Gazz.  Osped.,"  March  i,  1903. 


SKRt)US   MEMBRANES.  459 

Bacteriology  of  Serositis. — Reference  has  already  been  mafle  to  the 
serous  membrane  inHammations  accompanyinji;  typhoid,  ])neumonia. 
inrtuenza,  erysipelas,  and  other  infectious  diseases  in  which  the  orj^an- 
ism,  entering  the  circulation,  localizes  in  one  or  more  serosa.  There  are 
a  number  of  bacteria  which  often  produce  serous  membrane  inflamma- 
tion without  evident  antecedent  infection  of  other  structures.  The 
pneumococcus  is  frequently  found  in  serositis.  According  to  Parker,' 
seventy-tive  ])er  cent,  of  the  cases  of  empyema  in  children  are  pneumo- 
coccal ;  exactly  what  ])roportion  of  these  are  metapneumonic — follow 
pneumonia — it  is  difticult  to  say.  Often  it  is  impossible  to  determine, 
with  any  degree  of  accuracy,  by  what  route  the  infection  occurred. 
When  the  pleura  is  involved,  it  is  reasonable  to  assume  that  the 
organism  entered  through  the  lungs;  in  primary  pneumococcal  menin- 
gitis the  infection  probably  traversed  the  facial  or  cranial  air  sinuses. 
It  seems  likely  that  pneumococcal  pericarditis  is  always  the  result  of 
hematogenous  infection.  According  to  Jensen,  pneumococcal  peri- 
tonitis results  from  infection  through  a  wound,  through  the  diaphragm, 
through  the  intestine  or  genital  tract,  by  the  blood,  or  from  pneumo- 
coccic  foci  in  an  abdominal  organ.  Ghon  states  that  pneumococcic 
peritonitis-  frequently  complicates  cancer  of  the  stomach.  The  pneumo- 
coccic forms  of  arthritis  are  hematogenous  in  origin  and  are  rarely 
primary.  The  serosae  particularly  prone  to  infection  by  the  gonococcus 
are  the  synovial  membranes  and  peritoneum.  Hunner  and  Harris 
were  able  to  collect  39  cases  of  gonococcal  peritonitis.^  Gonorrheal 
rheumatism  is  essentially  a  synovitis,  although  other  joint  stnictures 
may  be  piffp'"^**'^  The  pyogenic  cocci  and  the  Streptococcus  pyogenes 
are  frequently  found  in  suppurative  inflammations  of  the  serous 
membranes.  McCollom  and  Blake  ^  report  two  instances  of  strp.p- 
tococrnl  ppntnmtis  in  .Snno  cnses  of  scarlet  fever.  In  270  cases  of 
peritonitis,  Dudgeon  and  Sargent'  found  the  Staphylococcus  pyogenes 
albus  in  108.  Manahan^  found  streptococci  alone  or  associated  with 
other  bacteria  in  about  fifty  per  cent,  of  the  cases  coming  to  autopsy. 
In  perforative  lesions  involving  the  intestine  or  appendix  the  colon 
bacillus  is  practically  always  present  and,  like  the  typhoid  bacillus, 
may  give  rise  to  peritonitis  without  demonstrable  lesion  in  the  con- 
tinuity of  the  intestinal  wall  (propagative  infection).  The  bacillus 
coli  is  not  infrequently  present  in  inflammations  of  serous  membranes 
other  than  the  peritoneum.  The  meningococcus'  is  the  usual  cause  of 
epidemic  cerebrospinal  meningitis  and  has  also  been  observed  in  peri- 
carditis and  pleurisy. 

*  "Brit.  Med.  Jour.,"  May  9,  1903,  p.  1081. 

'"Wien.  klin.  Woch.,"  March  10,  1904,  p.  267.  Mathews.  "Annals  of  Sur- 
gery," Nov.,  1904,  p.  698.  de  Quervain,  "Corresp.  Blatt.  f.  Schweizer  Aertze," 
vol.  xxxii,  No.  15. 

'  Dowd,  "Annals  of  Surgery,"  Feb..  1902.  Hunner  and  Harris,  "Bull,  of 
Johns  Hopkins  Hospital."  June,  1902,  vol.  xiii,  ]).  135.  Putman.  "The  Post- 
eraduate,"  Oct.,  1902,  p.  1117.  Krause,  "Berl.  klin.  Woch.,"  Slay  o,  1904. 
Huber,  "Arch,  of  Pediatrics,"  Dec.  1004.  Galvaj:^e,  "Annales  des  Maladies  des 
Organes  Genito-Urinaires,"  1904,  No.  13,  p.  iov>.  Wynn.  "Lancet."  Feb.  11. 
1905,  p.  25--     See  also  Gonococcus,  y».   107. 

*  "Boston  Med,  and  Surg,    lour.,"  Dec.   10,   1903. 

*  "Lancet,"  Feb.  25,  1905,  v.  474.  N 

*  "Boston  Med.  and  Surg,  jour.."  March  23.  1005,  p.  346. 
'  See  page  iii;   also  Cerebrospinal  Meningitis. 


460  SPECIAL  PATHOLOGY. 

The  tubercle  bacillus^  occupies  an  all-important  relation  to  the 
production  of  serous  membrane  inflammations;  all  serosae  are  suscep- 
tible to  its  action,  but  the  pleurae,  pericardium,  meninges,  and  peri- 
toneum are  more  frequently  involved  than  the  synovial  membranes, 
tendon-sheaths,  or  bursae.  There  is  little  reason  for  believing  that 
the  serositis  produced  by  the  tubercle  bacillus  is  ever  primary,  although 
cases  occur  in  which  it  is  difficult,  if  not  impossible,  to  demonstrate 
the  initial  infection  from  which  the  bacillus  reached  the  serous  membrane.^ 
The  frequency  of  pleurisy  due  to  the  tubercle  bacillus  is  variously 
estimated  at  from  fifty-five  per  cent,  to  ninety-four  per  cent,  of  all  cases 
observed;  the  studies  of  Eichhorst  indicate  that  sixty  per  cent,  to 
sixty-five  per  cent,  of  those  with  serous  effusion  contain  fluid  capable 
of  producing  tuberculosis  in  inoculated  animals. 

Among  the  bacteria  occasionally  found  in  serositis  may  be  men- 
tioned the  bacillus  of  Friedlander,  Bacillus  pyocyaneus,  Bacillus  pyo- 
genes foetidus,  Bacillus  aerogenes  capsulatus,  and,  although  less  com- 
monly, other  anaerobic  bacteria.^  In  exceptional  cases  the  condition 
is  produced  by  members  of  the  actinomyces  group. ^  Schwartz''  reports 
a  case  of  appendicitis  and  encysted  peritonitis  due  to  a  yeast. 

Classification  of  serous  membrane  inflammations  may  be  based  on 
the  etiology,  extent,  and  duration,  or  the  clinical  and  anatomic  characters. 
Those  inflammations  not  due  to  bacteria  or  their  toxins  were  called  sim- 
ple, and  distinguished  from  the  infective  by  the  absence  of  micro-organ- 
isms. Extended  knowledge  indicates  that  serositis,  in  practically  all 
its  forms,  is  infective  in  origin,  and  the  more  recent  tendency  is  to  give 
up  the  names  simple  pleurisy,  simple  pericarditis,  etc.  Idiopathic  or 
cryptogenic  inflammations  include  those  in  which  the  source  of  the  infec- 
tion can  not  be  determined.  Inflammations  in  which  the  infection  was 
introduced  from  without,  as  by  operation  and  other  wounds,  are  called 
exogenous.  Those  resulting  from  invasion  of  a  serosa  by  infectious 
processes  originating  in  some  adjacent  structure  are  known  as  endog- 
enous, and  include  the  so-called  secondary  form  of  serous  membrane 
inflammation. 

In  certain  cases  names  are  utilized  to  indicate  the  extent  of  the  in- 
flammatory process;  in  localized  or  circumscribed  serositis,  a  part  only 
of  the  affected  serous  membrane  is  involved;  in  the  general  or  diffuse 
form  the  entire  serosa  is  inflamed.  Parietal  and  visceral  forms  have  been 
described.  Some  of  the  localized  types  of  serous  membrane  inflamma- 
tion have  received  special  names  indicating  the  particular  part  of  the 
serosa  aft'ected.  As  examples  of  this  method  of  classification  may  be  men- 
tioned pelvic  peritonitis,  diaphragmatic  pleurisy,  interlobar  pleurisy, 
apical  pleurisy,  and  basilar  meningitis. 

The  terms  acute  and  chronic,  as  applied  to  serous  membrane  inflamma- 
tion, usually  imply  something  more  than  mere  duration,  and  constitute 

^Cornet,  "Tuberculosis,  Acute  General  Miliary  Tuberculosis,"  Nothnagel's 
Encyclopedia,  American  edition,  1904,  p.  189.  Grober,  "Centralbl.  f.  inn.  Med.," 
1902,  No.  10.  Murray,  "Lancet,"  1902.  Bonney,  "Med.  News,"  Feb.  18,  1905, 
p.  289. 

'  Ghon  and  Sacs,  "Centralbl.  f.  Bakt.,"  Jan.  25,  1905,  p.  i,  and  Feb.  18,  1905, 
p.  131. 

^  MacCallum,  "Centralbl.  f.  Bakt.,"  May  14,  1902,  also  Mathews,  "Practi- 
tioner," Feb.,   1905,  p.   197. 

*  "Revue  de  Chir.,"  July,  1903,  p.  122. 


SEROUS   MKMUKANES.  46  I 

a  basis  u]»on  which  anatomic  classification  rests.     The  study  of  the  mor- 
bid anatomy  of  serous  membrane  inflammations  renders  it  ])ossible  to 
divide    the    acute    into    (i)  serous,    (2)  serofibrinous.    (O  fibrinous    or      ^ 
plastic,   and   (4)  suppurative.     Some  of   the   chronic   intlainniations  (A  .^\'^y' 
the  serous  membrane  mav  be  little  more  tlian  the  e'onsc(}ucnccs  of  thc^_  j  Y^ 

acute  lorms^    It  is  ])()ssiblc,  however,  to  recot^nizc  certam  suhdi visions ~  ' 
and  more  or  less  distinct  types.     XichoUs'  sui,'i,'ests  dividing,'  the  chronic 
inflammations  into  (i)  exudative.  (2)  exudative  and  adhesive,  and  (3) 
chronic  lu]icr]ilastic:  tlie  latter  is  also  called  progressi\Te  hyaloserositis. 

Morbid  Anatomy  of  Acute  Serositis. — -In  this  form  it  is  usually  possible 
to  recognize  definite  stages  which  often  blend  so  that  distinct  separation  of 
one  from  another  may  be  quite  impossil)le.  In  some  cases  the  inflamma- 
tion seems  to  linger  in  one  stage  or  the  phenomena  may  be  restricted  to 
those  that  are  ordinarily  observed  in  this  particular  period  in  the  evolu- 
tion of  a  serositis.  In  the  first  stage  the  membrane  is  dry,  red  and  injected, 
slightly  opaque  and  perceptibly  roughened.  It  may  be  sticky,  and  it 
alwavs  presents,  over  the  inflamed  area,  a  dull  or  velvety  surface,  in  con- 
trast to  the  shining  luster  of  the  normal.  Histologically,  at  this  stage 
the  subserous  capillaries  are  distended  with  blood.  The  areas  of  capil- 
lar\-  hyperemia  are  scattered  over  the  membrane  irregularly,  and  appear 
as  though  smears  of  carmin  stain  had  been  daubed,  here  and  there,  over 
the  affected  membrane;  the  diffuse  character  of  the  discoloration  has 
been  likened  to  a  blush;  rarely,  if  ever,  is  the  hyperemia  capillary  dis- 
tention universal.  The  morbid  physiology  is  shown  in  the  friction  sounds 
discernible  on  auscultation,  and  the  fremitus,  both  of  which  are  due 
to  the  friction  of  roughened  and  dry  surfaces  rubbing  against  each 
other.  The  pain  of  this  stage  is  probably  the  result  of  mechanical  injury 
to  the  ner\-e  filaments,  and  chiefly  to  the  irritation  of  the  nerves  by  bac- 
terial toxins  and  the  chemic  bodies  engendered  by  the  changes  in  cell 
metabolism.  It  seems  probable  that  the  fever  is  due  to  the  same  bodies 
entering  the  circulation. 

The  second  stage  corresponds  to  the  formation  of  the  exudate,  and 
might,  with  propriety,  be  called  the  stage  of  exudation.  The  liquor 
sanguinis  escapes  from  the  distended  capillaries,  and,  upon  reaching  the 
surface  of  the  membrane,  splits  into  fibrin  and  serum,  the  former  coating 
the  surface  of  the  serosa,  the  latter  finding  room  in  the  cavity.  With 
the  escape  of  the  plasma  the  leukocytes  migrate  into  the  fibrinous  and 
serous  exudate  It  is  also  probable  that  the  flattened  connective-tissue 
cells  are  to  some  degree  detached.  Should  the  exudate  be  slight,  and 
should  the  serum  be  rapidly  absorbed,  but  little  remaining  in  the  cavity, 
clinically,  the  inflammation  is  spoken  of  as  plastic  or  fibrinous:  if,  how- 
ever, the  effusion  be  rich  in  serum  and  poor  in  cells  and  fibrin,  the  process 
is  called  serous.  In  the  serofibrinous  serositis  the  exudate  is  usually  large, 
and  the  fibrin  and  cells  abundant.  If  the  first  stage  be  called  the  stage  of 
engorgement  or  hyperemia,  the  appearance  of  the  exudate  initiates  the 
stage  of  exudation. 

In  this  stage  the  membrane  is  found  either  partly  or  completely  cov- 
ered with  fibrin,  the  degree  of  cohesion  being  dei)endent  upon  the  thick- 
ness of  the  layer  and  upon  its  age.     The  fluid  in  the  serous  sac  differs 

*  "American  Medicine,"  June  21.  1902,  p.  1062:  "Jour.  Amer.  Med.  Assoc.," 
March  14.  1903.  p.  606:  and  "Studies  from  the  Royal  Victoria  Hospital,  Mon- 
treal," April,  1902.  vol.  1,  No.  3. 


462  SPECIAL  PATHOLOGY. 

from  the  normal  serum  in  that  it  is  opaque  and  contains  fibrinous  floccuH ; 
the  opacity  is  partly  the  result  of  the  fibrin  present,  but  is  chiefly  due 
to  the  large  number  of  suspended  leukocytes.  The  soft,  downy  mass  of 
fibrin  hanging  in  shreds  has  led  to  the  heart  at  this  stage  being  called  the 
cor  villosnm;  it  is  also  known  as  the  cor  Jiirsntum.  (See  Fig.  232.) 
Laennec  compared  the  appearance  to  that  resulting  from  the  separation 
of  two  smooth  surfaces  of  wood  between  which  had  been  pressed  a  pat  of 
butter,  and  hence  the  term  "bread-and-butter  appearance."  The  thick, 
shaggy  layer  may  remain  adherent  to  the  membrane,  or  the  fibrin  may 
be  whipped  off  to  a  greater  or  lesser  degree  by  the  moyements  of  the  in- 
closed organ.  The  color  yaries.  Commonly  the  inflammatory  exudate 
is  white  or  yellowish-white:  sometimes,  howeyer,  it  is  brown,  yellowish- 
brown,  or  eVen  brownish-red.  These  modifications  in  color  are  due  to 
the  dissolution  of  hemal  elements  in  the  exudate.  In  the  earlier  stages 
the  exudate  may  be  readily  stripped  from  the  serous  surface,  and  may 
even  show  lamination,  as  though  successiye  layers  had  been  thrown  out, 
the  lowermost  and  oyerlying  strata  being  pushed  upward  by  the  succeed- 
ing layer.  The  amount  of  serum  present  in  the  cavity  determines 
whether  inflammation  should  be  called  in  this  stage  dry  or  moist.  Where 
absorption  has  been  rapid  and  the  serum  has  thereby  been  removed  as 
rapidly  as  formed,  or  nearly  so,  the  serositis  is  said  to  be  dry,  plastic,  or 
fibrinous. 

The  studies  of  Beattie^  were  directed  toward  determining  the  period 
at  which  the  different  elements  appeared  in  the  inflammatory  exudate; 
working  with  various  bacteria,  including  pyogenic  staphylococci  and 
tubercle  bacilli,  and  also  with  foreign  bodies,  he  found  that  during 
the  first  two  hours,  following  the  application  of  the  irritant,  the  fluid 
was  clear,  resembling  normal  serum.  In  from  one  to  two  hours  after 
the  injection  the  polymorphonuclear  cells  began  to  appear  in  numbers, 
and  by  the  third  hour  were  greatly  increased.  In  from  four  to  eight 
hours  migration  of  the  mononuclear  leukocytes  began,  and  by  the  twelfth 
hour  these  cells  were  fairly  abundant.  Turbidity  and  viscosity  of  the 
fluid  became  progressively' more  intense,  reaching  the  maximum  about 
twenty-four  to  forty-eight  hours  after  the  introduction  of  the  irritant. 
After  this  time  the  'character  of  the  fluid,  in  fatal  cases,  was  different 
from  that  in  animals  which  recovered.  In  nonfatal  cases  the  fluid 
increased  and  was  more  abundant  in  fifty -four  to  seventy -two  hours; 
during  this  time  the  exudate  appeared  watery,  by  the  fourth  day  it  was 
clear,  and  bv  the  fifth  normal.  In  these  cases  the  polymorphonuclear 
cells,'  abundant  during  tne  first  day  and  a  half,  became  less  conspic- 
uous and  disappeared  between  the  sixtieth  and  seventieth  hours.  Beat- 
tie  is  of  the  opinion  that  the  mononuclear  cells  are  derived  from  the 
blood  and  also  from  the  endothelium,  particularly  of  the  omentum. 
The  polymorphonuclear  leukocytes,  lymphocytes,  hyaline  cells,  endothe- 
lium, and  plasma  cells,  all  manifest  varying  degrees  of  phagocytic 
power. 

The  specific  gravity  of  the  fluid  is  usually  higher  than  m  the  pure 
transudates  and  may  be  1.040;  commonly  it  varies  between  1.015  and 
1.025.  As  a  result  of  destruction  of  the  leukocytes,  the  xanthin  bases 
are  increased.     Galdi  and  Appiani^  have  shown  that  the  quantity  of 

1  "Jour,  of  Path,  and  Bact.,"  vol.  viii,  June,  1902. 
^  "  Rif .  Med.,"  Dec.  14,  1904. 


SEROUS  MEM BRAN KS.  463 

uric  acid  is  i)roportionate  to  the  specific  gravity,  the  total  amount  of 
hydrogen,  and  (luantity  of  proteids,  all  of  which  are  increased.  Urea, 
sugar,  and  peptone  are  usually  present.  Coriat'  has  demonstrated 
Bence- Jones  albumin  in  the  fiuid  from  pleuritic  effusion. 

The  amount  of  accumulated  exudate  in  the  pericardial  cavity  may 
he  from  loo  c.c.  to  200  c.c;    occasionally  as  much  as  a  liter,  and  rarely 
more.     According  to  Aporti,^  pericardial  effusions  amounting  to  less 
than  150  c.c.  to  250  c.c.  can  not,  with  certainty,  be  clinically  detected, 
and  distensibility  of  the  pericardium  does  not  permit  the  rapid  forma- 
tion of  an  exudate  exceeding  650  c.c.  to  700  c.c.     When  the  fiuid  accu- 
mulates more  slowly,   has  been  withdrawn  and  permitted  to  reforni, 
or  is  purulent,  the  pericardial  sac  slowly  yields  and  may  readily  contain 
larger  amounts.     When  the  quantity  of  fluid  exceeds  200  c.c.  or  300  c.c. 
the    intrapericardial    pressure    becomes   notably    augmented.      Glynn' 
found  that  in  an  accumulation  of  approximately   700  c.c,  in  a  boy 
aged   seventeen  years,   the  pressure   at  the  beginning  of  paracentesis 
pericardii  was  -(-  '2.1  cm.,  and  at  the  end  of  the  operation  fell  to  — 2  cm. 
The  quantitv  of  fluid  in  the  pleura  is  influenced  by  the  presence  of  ad- 
hesions,  the'  character   and   duration   of   the   inflammation,   and   com- 
monly is  larger  on  the  right  than  on  the  left  side.     Of  the  200  cases 
studied  by  Delafield,^  the  quantity  was  between  3000  c.c.  and  3500  c.c. 
in  6;  between  2000  c.c.  and  2500  c.c.  in  23;    1500  c.c.  to  2000  c.c.  in  37; 
1000  c.c.  to  1500  c.c.  in  55;    500  c.c.  to  1000  c.c.  in  49;    and  in  30  cases 
there  was   between  100  c.c.    and  400  c.c.     The  quantity  of  fluid  may 
far  exceed  the  maximum  observed  in  Delafield's  cases.     The  changes 
in  pressure  result  in  the  lung  being  displaced  backward,  upward,  and 
inward  toward  the  hilum  of  the  organ,  the  mediastinal  tissues  are  forced 
toward  the  unaffected  side,  and  the  diaphragm  descends.      During  the 
earlier  stages  of  the  process  spasticity  of  the  intercostal  muscles  narrows 
the  space  between  the  ribs,  and  later  degenerative  and  necrotic  changes 
affecting  these  structures"'  may  be  followed  by  relaxation  and  inter- 
costal bulging.     Rohrer^  was  the  first  to  demonstrate  structural  changes 
in  the   diaphragm  resulting   from  inflammation   of  either  one   of  the 
three  contiguous  serosae;    I  have  been  able  to  verify  his  obser\'ations." 
In  manv  cases  of  pleurisy  the  lymphatics  of  the  pulmonary  tissue  con- 
tain leukocvtes  and  filirin,  and  similar  bodies  have  been  found  in  the 
Ivmph-nodes  of  the  hilum  of  the  lung.     In  inflammation  of  the  peri- 
toneum the  analogous  abdominal  structures  show  essentially  the  same 
changes.     In   both   locations   the   alteration   i'-.    produced   by   irritants 
traversing   the   lymphatics   draining   the    affected    area.     In    this   way 
the   lyniphoi^cnoiis    interstitial   piiciinuviia,   which   may   be   suppurative 
or,  in  the  more  chronic  cases,  fibroid,  is  produced.     In  the  heart  the 
myocardium,    contiguous    to    the    inflamed    serosa,    is    frequently    de- 
generated and  may  be  infiltrated  by  the  inflammatory  products  (pcri- 

'  "Amer.  Jour,  of  Med.  Sci.."  Oct.,  1903,  p.  631. 
'  "Centralbl.  f.  inn.  Med.."  Julv  14.  iQoo. 

*  "Jour.  Amer.  Med.  Assoc.,"   tune  i,  igoi. 

•  "Amer.  Jour,  of  Med.  Sci.,"  Dec.  igoi.  p.  030. 

'Coplin,  'Amer.  Jour,  of  Med.  Sci.,"  May.  1904;    "Proceed,  of  the  Path.  Soc. 
of  Phila.,"  Jan.  28.  1904. 

•"Maryland  Med.  Jour.."  Sept..  1902.  p.  391- 

^  For  iflustration  showing  coagulation  necrosis  in  intercostal  muscles  see  tig. 

143.  P-  251. 


464 


SPECIAL  PATHOLOGY. 


cardiomyocarditis).  In  meningitis*  the  contiguous  nervous  tissue  is 
the  seat  of  manifest  degenerative  changes  and  the  nerve-trunks  of 
the  affected  area  are  infiltrated.  Laignel-Lavastine^  has  shown  that 
in  peritonitis  the  solar  plexus  is  affected;  in  the  acute  manifestations 
the  lesions  are  essentially  parenchymatous ;  in  the  chronic  cases  the  inter- 
stitial changes  are  more  conspicuous. 


E 


A 


Fig.  232. — Heart  Showing  Villous  Pericarditis;  .\scending  and  Transverse  Portion  of  Arch  of  Aorta, 
Showing  Aneurysm  with  Contained  Clot,  and  Ruptures  into  Pulmonary  Artery  and  Pericardium. 

A.  Part  of  the  parietal  pericardium,  showing  the  fibrinous  deposit  and  minute  villi,  h  similar  appearance  is  pres- 
ent on  the  visceral  pericardium.  B.  Innominate  artery.  C.  Left  common  carotid.  D.  Left  subcla\ian. 
E.  Catheter  passing  through  the  dot  in  the  aneurysm  of  the  aorta  and  into  the  pulmonary  artery,  following 
the  course  of  the  rupture  into  the  last-named  vessel.  F.  Continuation  of  the  same  catheter  into  the  right 
ventricle  through  the  orifice  of  the  pulmonary  artery.  A  section  was  cut  out  of  the  catheter  in  order  to  show 
position  of  aortic  cusps.  G.  Catheter  passed  from  the  aneurysmal  cavity  through  the  thrombus  and  pericar- 
dium and  entering  the  pericardial  cavity  into  which  the  aneurysm  ruptured.  There  were  clinical  and  patho- 
logic reasons  for  believing  that  the  rupture  into  the  puhnonary  artery  was  old — probably  several  weeks. 
The  rupture  into  the  pericardial  ca\'ity  was  recent,  and  had  been  the  immediate  cause  of  death.  H.  Inferior 
thyroid  artery.  /.  Wall  of  aneurysm.  /.  Laminated  thrombus,  through  the  center  of  which  the  circulation 
had  been  maintained.  Above  the  leader  from  the  letter  /  are  shown  four  slit-like  areas  that  contained  dark 
dots  of  ijlood  (red  thrombi).     The  remainder  of  the  thrombus  was  white. 

The  morbid  histology  of  this  stage  is  characterized  by  a  reduction 
in  the  size,  and  a  less  crowded  condition,  of  the  subserous  capillaries, 

'  See  Cerebrospinal  Meningitis. 

2  "Arch,  de  Med.  exper.  et  d'Anat.  path.,"  Jan.,  1905,  p.  54. 


SEROUS   MKMHUANKS. 


4fJ5 


m 


-r^M^^ 


which  have  been  largely  relieveil  by  the  escape  of  those  materials  enter- 
ing into  the  formation  of  the  exudate.  The  layer  of  fibrin,  on  section 
and  in  teasings.  contains  abundant  leukocytes  and  a  few  erythro- 
cytes; the  endothelial  cells  will  be  seen  desquamating,  the  process,  at 
points,  being  laminated;  masses  of  these  elements  occur  far  up  in  the 
fibrinous  layer. 

The  morbid  physiology  of  the  exudative  stage  is  manifested  by  the 
altered  functional  activity  of  the  encumbered  viscus.  or  viscera,  and  the 
results  of  the  toxic  action  of 

metal)olic    products    derived  ^.   . _    '' 

from  the  bacteria  and  tissues. 
If  an  abundant  exudate  be 
present,  pressure  will  influ- 
ence the  action  of  the  en- 
vironed organ  and  will  me- 
chanically impede  its  func- 
tion. Friction  sounds,  when 
previously  present,  disappear 
if  the  exudate  be  sufficient  to 
force  the  two  layers  apart  and 
the  fibrin  covers  the  rough- 
ened serous  surfaces.  The 
fever  may  be  kept  up  by  the 
absorption  of  the  metabolic 
products;  these  also  induce, 
not  uncommonly,  phenomena 
not  usually  due  to  pyrexia 
alone:  e.  g.,  suppression  of 
excretion  and  nervous  symp- 
toms. The  fibrinous  exudate 
may  so  conceal  and  obstruct 
access  to  the  lymphatic  and 
vascular  exits  as  to  preclude 
resorption  of  the  serum  or 
its  pyrogenous  constituents, 
and  hence  no  systemic  phe- 
nomena due  to  their  absorp- 
tion will  be  manifest.  When 
percussion  and  auscultation 
are  permissible,  as  in  pleurisy, 
pericarditis,  and  peritonitis, 
the     phenomena     associated 

with  the  presence  of  solids  or  liquids  in  the  affected  cavities  may  be 
found:   c.  g.,  dullness. 

Exactly  how  long  the  stages  of  engorgement  and  exudation  may 
last  can  not  be  approximated  with  any  degree  of  accuracy;  their  dura- 
tion varies,  the  conditions  inducing  the  variation  lieing  but  indifferently 
understood;  the  cause,  the  severity  of  the  attack,  the  condition  of  the 
patient,  whether  weak  or  strong,  are  undoubted  determining  factors. 
The  stages  may  be  prolonged  or  brief,  and  just  what  determines  this 
can  not  always  be  definitely  stated;  sooner  or  later,  if  the  patient  sur- 
vives, repair  proiec<ls  as  follows: 

31 


Fig 


233. — Vertical  Sectio.v  through  an  Inflamei)  Serosa 
after  the  formation  of  the  fibrinous  excdate. — 
(Schmaus.)     X  250  diameters. 

Subpericarflial   (at.     b.  Swollen   membrane,   tin-   surface  of 
which  is  contiguous  to  and  Mi-nils  with  ■  tilirin- 

ous deposit  f.     f.   L;ivorof  t'llinn  in  whi.  .>lcu- 

kfKVtcs.  (/,  and  into  which,  at  r,  are  devi  1  1  sseN. 


466 


SPECIAL  PATHOLOGY 


.  In  this  stage  the  connective-tissue  cells,  and  possibly  some  of  the 
mononuclear  leukocytes,  present  in  the  wall  of  fibrin  proliferate  and  con- 
vert the  laver  into  embrvonic  tissue;  young  blood-vessels  are  developed 
from  the  subserous  layers,  and  lymphatic  connection  is  re-established. 
The  facilitv  with  which  voung  blood-vessels  shoot  up  into  the  new  tissue 
is  marvelous,  and  to  the' rapidity  with  which  this  process  of  organization 
develops,  modern  surgery  owes  many  of  its  most  brilliant  achievements. 


i\.i!T',''^ 


MM 


•jm-^.'^: 


D    1 


1 


'■■a 
■1 


Fig.  2Z4- — Intercostal  Muscle. 

Transverse  section,  from  a  case  of  epipneumonic  pleurisy, 
showing  dissociation  of  tibers,  interfascicular  leukocy- 
tic infiltration,  and  slight  fibrin  formation.  Tissue 
fixed  in  Zenker's  fluid;    hemato.xylin  and  cosin  stain. 

A,  .4,  A.  Granular  and  fragmented  muscle-fibers.  B.  Ac- 
cumulation of  leukocytes  and  fibrin  around  and  extend- 
ing between  the  muscle-fibers.  In  some  areas  the 
change  is  more  marked  than  in  others,  and  at  points 
many  polymorphonuclear  leukocytes  can  t)e  seen. 


^^^ 


Fig.  235.- 


-IXTERCOST.AL    MuSCLE,  C.4SE    OF 
ES1PYEM.\. 

Transverse  section,  from  a  case  of  suppurative 
pleurisy  of  several  months'  duration,  showing 
ad\anc'ed  fibrosis  and  lipomatous  change. 
Tissue  fi-xed  in  Zenker's  fluid;  hematoxylin 
and  eosin  stain. 

A.  One  of  several  granular  fibers,  some  of  which 
are  fragmented  and  undergoing  absorption. 
B.  A  small  group  of  greatly  shrunken  muscle 
fibers.  C.  Relatively  large  mononuclear  cell, 
not  very  abundant,  but  commonly  associated 
with  fibroblastic  elements.  D.  The  leader 
from  this  letter  passes  between  two  imperfectly 
presented  fat  bodies,  a  number  of  wliich  are 
present  in  the  newly  forming  or  formed  fibrous 
tissue.  The  fat  content  is  scanty  in  the  par- 
ticular field  from  which  this  drawing  was  made. 


The  leukocvtes  and  voung  proliferating  connective-tissue  cells,  the  prog- 
eny of  the  endothelial  lining,  constitute  a  small,  round-cell  mass  known 
as 'embrvonic  or  formative  tissue;  when  the  young  blood-vessels  per- 
meate this  structure,— in  other  words,  when  it  becomes  vascularized, — 
it  is  known  as  granulation  tissue.  The  next  step  is  the  organization  of 
this  into  fibrous  connective  tissue,  which,  becoming  smoothed,  gives  a 
surface  functionallv  normal ;  but  as  all  organizing  tissue  manifests  a  ten- 


SEROUS   MEM  BRAN  KS. 


467 


-■■■■.  >^^^  ■ 


V-vr- 


:5^"^ 


'H*^. 
■^V- 

/■/•' 


^fcijj^fiSifc.'-^'aS^ 


-*,: 


V.  :'^^.'^  : 


:>J'  i-  .--■  .=*. 


:^.^e^ 


dency  to  contract,  grave  results  may  ensue  in  tlie  structures  V)eneath. 
Following  meningeal  inflammation,  ])ressure  ujjon  nerves  leaving  the 
brain  mav,  by  constriction,  lead  to  degeneration  and  entire  loss  of  con- 
ducting power.  ])aralyses.  blindness,  or  deafness  being  thereby  produced. 
Over  the  lung  the  contraction  may  preclude  re-exjjansion  and  favor  the 
continued  presence  of  the  serous  exudate.  A  band  around  the  intestine 
may  cause  narrowing,  and  event- 
ually oV)struction.  In  the  peri- 
cardium, however,  it  is  not  l)e- 
lieved  that  the  contraction  does 
sufficient  harm  to  merit  consider- 
ation. If  adhesions  attach  the 
heart  to  contiguous  structures — 
chest  wall,  diaphragm,  or 
mediastinum — the  expansion  of 
the  organ  may  be  little  influ- 
enced, the  principal  danger  lying 
in  the  fact  that,  at  each  contrac- 
tion, the  attached,  often  rigid 
structures  pull  upon,  and  resist 
reduction  in  the  size  of  the  heart 
necessary  in  order  to  empty  its. 
cavities.  Riesman^  believes  that 
pericarditis  is  more  damaging  to 
the  heart  than  is  endocarditis. 

Adhesions  between  two  layers 
of  a  serous  membrane — c.  t.'..  the 
pericareiium — are  brought  about 
hv  the  two  fibrinous  surfaces 
coming  together  at  any  stage  of 
the  inflammation  before  organiz- 
ation is  well  under  way.  In  the 
recent  state  the  fibrinous  layers, 
if  brought  in  contact,  are  at  once 
agglutinated,  and  it  is  not  im- 
probable that,  in  the  embryonic 
tissue  stage  of  the  inflammation. 
or  even  when  vascularization  is 
well  advanced,  cohesion  of  the 
two  surfaces,  followed  by  an  or- 
ganized adhesion,  is  possible. 
After  agglutination  of  the  fibrin- 
covered  surfaces,  or  in  the  later 
stages  when  the  contact  is  in- 
timate and  prolonged,  the  young 
blood-vessels  anastomose  and 
pass  from  one  side  to  the  other, 

organization  into  fibrous  tissue  ensues,  following  the  lines  already  indi- 
cated, and  an  adhesion  is  the  result.^  The  constant  movement  of  the 
heart  probal>ly  precludes  general  union  of  the  pericardial  layers  at  a 

'  "Amer.  Jour,  of  Med.  Sci.,"  Sept.,  1904,  p.  466. 
'Compare  with  union  by  first  intention,  p.  301. 


-:=x^- 


c»-« 


Fig.  136. — Pfricardil'm  (over  Auricle);  ArvTE  Sero- 
HBRiNous  Pericarditis  Enlrafted  on  a  Serosa  the 
Site  of  Past  Inflammations. 

A.  P<mion  of  auricular  myocardium.  .4  lo  B.  GrcaUy 
thickened  pericardium  CDmposed  of  relatively  dense 
iy>rous  lis.sue,  u()iin  ihi-  surtace  of  which  is  attached 
the  product  of  a  recc-nl  inll.imni.itiim;  the  latter  is  com- 
pisfd  of  fibrin  and  formative  elements,  the  former 
ha\inK  largely  disapix-ared.  C',  C'.  C".  Three  yininn 
vessels;  many  others  can  l)c  seen  in  the  drawing.  The 
surface.  alx)vc  the  upix.-r  t",  has  not  been  reached  by 
the  young  vessels. 


468 


SPECIAL  PATHOLOGY. 


single  attack,  but  in  the  pleura  it  is  not  improbable  that  the  entire  sac 
mav  be  obliterated  by  the  first  pleurisy  that  occurs,  especially  if  the 
process  be  of  the  plastic  type.  Whether  adhesions  form  or  not,  the  serous 
membrane  remains  permanently  thickened.  Into  this  new  tissue  lime 
salts  or  fat  may  be  deposited.  In  the  former  instance  the  condition  is 
known  as  calcification;  in  the  latter,  as  fatty  infiltration.  When  the  in- 
flammatory process  is  associated  with  the  deposit  of  lime  salts,  the  terms 
pleuritis  petrificans,  pericarditis  petrificans,  or  calcifying  serositis  may  be 
applied. 

An  opportunity  to  study  the  formation  of  adhesions  is  afforded  in 
almost  all  surgical  operations  upon  serous  surfaces.  When  a  wound 
involves  the  intestine  the  two  serous  surfaces  are  brought  together  by 
sutures;  along  the  line  of  contact  an  exudation  of  liquor  sanguinis  and 
the  migration  of  leukocytes  occur;  the  former  separates  into  fibrin  and 

serum,  the  fibrin  forming  a 
temporary  cement  and  bind- 
ing the  two  apposed  surfaces 
together.  The  rapidity  with 
which  this  preliminary  ag- 
glutination occurs  is  well 
illustrated  in  the  case  re- 
ported by  Oliver,^  in  which, 
after  five  hours,  the  sutured 
intestinal  wall  had  formed  a 
water-tight  joint.  Embryonic 
tissue  is  formed,  followed  by 
granulation  tissue,  and  later 
by  a  cicatrix  that  unites  the 
surfaces  along  the  line  of 
suture.  This  cicatrix  is  an 
adhesion,  the  histology  and 
mode  of  development  of 
which  are  practically  identi- 
cal with  the  formation  of 
adhesions  in  pericarditis, 
pleurisy,  inflammations  of 
tendon-sheaths,  etc.  The 
closing  or  obliteration  of  the 
sac  for  the  cure  of  hydrocele  is 
brought  about  by  inducing  an  inflammation  of  the  serous  membrane  and 
favoring  adhesion  of  the  walls  by  removal  of  the  contents,  thereby  permit- 
ting collapse.  The  surgeon  withdraws  the  contents  and  brings  about  an 
inflammation  of  the  lining  membrane  by  gently  scratching  the  serous  sur- 
face or  by  injecting  an  irritant,  such  as  iodin.  Such  injury  is  followed  by 
redness  (hyperemia),  the  formation  of  a  fibrinous  exudate,  and  agglutina- 
tion of  the  collapsed  walls;  proliferation  of  the  connective-tissue  cells 
leads  to  repair,  just  as  indicated  in  the  foregoing  description  of  adhesion 
formation.  In  this  case  adhesions  are  expected,  and,  as  in  the  union 
of  two  serous  surfaces  when  sutured,  the  success  of  the  operation  de- 
pends upon  the  development  of  new  fibrous  tissue  through  which  perma- 
nent adhesion  and  obliteration  of  the  serous  cavity  are  secured. 
*  "Cincinnati  Acad,  of  Med.,"  Jan.  28,  1901. 


^o ■ 


Fig.  237. — Section  through  Margin  or  Adhesion  Between 
Parietal  and  Visceral  Pleura. 

A.  Part  of  fibrous  sheath  of  intercostal  muscle,  beneath  which 
is  a  stratum  of  fat.  B.  Parietal  (costal)  pleura.  C.  Vis- 
ceral (pulmonary)  pleura.  D.  Interlobular  septum  some- 
what thickened.  E.  Adhesion  composed  of  formed  and 
newly  forming  fibrous  tissue  continuous  with  similarelemenls 
in  the  costal  and  pulmonary  pleura. 


SEROUS  MEMBRANES.  469 

Suppurative  serositis  results  from  infection  of  a  serous  membrane  by 
l)acteria  introduced  from  without,  as  by  wounds  and  injuries,  or  from 
some  bodv-cavity  nt)rmally  containing  microorganisms,  such  as  the  ah- 
mentarv  canal,  or  is  tlie  result  of  extension  of  infection  from  a  viscus 
covered  bv  the  serosa;  sometimes  the  infecting  germs  reach  the  serous 
membrane  by  the  blood-stream,  and  occasionally  through  the  lymi)hatic 
vessels.  Suppuration  in  the  peritoneum  (pyoperitoneum)  is  due  to 
infection  from  some  intra-abdominal  viscus,  as  the  ai)pendix,  perforated 
intestine,  duodenum  or  stomach,  infections  of  the  gall-blarldcr  and  liver, 
abscesses  of  the  spleen,  kidney,  pararenal  structure,  or  abdominal  wall; 
the  bacteria  may  enter  the  peritoneum  from  the  genito-urinary  and 
reproductive  organs.  In  the  female  the  uterus  and  its  appendages 
frequently  constitute  the  atrium  through  which  infection  occurs.  Hem- 
atogenous and  Ivmphogenous  infections  occur,  Imt  are  less  frequent. 
Occasionallv  infection  results  from  rupture  of  mesenteric  or  retroperi- 
toneal Ivmph-nodes.  It  is  to  be  remembered  that  by  propagative  infec- 
tion bacteria  may  pass  through  the  wall  of  a  hollow  viscus  (intestine, 
gall-bladder,  uterus,  etc.)  in  the  absence  of  any  structural  alteration  that 
could  be  called  a  perforation.  The  peritoneum  may  be  infected  from 
the  thoracic  serosa?,  or  bv  wounds  from  without.  Suppurative  serositis 
affecting  the  pleura  (empyema,  pyothorax,  suppurative  pleurisy)  com- 
monlv  results  from  extension  from  the  lung,  particularly  after  pneu- 
monia (especially  in  children),  and  in  tuberculosis  associated  with  cavity 
formation ;  less  commonly  the  infection  reaches  the  pleura  from  disease  of 
the  thoracic  wall,  esophagus,  lymph-nodes,  or  other  mediastinal  tissue, 
or  from  some  diaphragmatic  organ,  as  the  liver,  spleen,  or  stomach. 
Septic  pulmonary  infarcts  and  gangrene  of  the  lung  are  sometimes 
causes;  the  pleura  is  occasionally  infected  from  the  l)lood-stream.  The 
disease  is  common  in  children,  particularly  between  the  first  and  fifth 
and  the  eighth  and  ninth  years.  Bythell  ^  is  of  the  opinion  that  the  con- 
dition is  always  secondary,  and  that  the  so-called  primary  cases  are  in- 
fections from  undiscovered  patches  of  pneumonic  consolidation.  Jure- 
svitsch-  attributes  the  so-called  idiopathic  empyemata  to  infection  from 
a  pulmonary  lymphangitis.  Penetrating  wounds  of  the  chest,  and  even 
l)lows  and  injuries  without  solution  in  the  continuity  of  the  thoracic 
wall,  mav  give  rise  to  empyema.  Echinococcal  disease  in  contiguous 
structures  mav  suppurate  and  infect  the  pleura. 

The  bacteriologv  oj  empyema  is  essentially  that  of  serositis.'  The  studies 
of  Bvthell.  Foulerton,*  Nathan,'  Cotton,"  and  others  may  be  epitomized 
in  the  statement  that  seventy-five  per  cent,  of  the  empyemata  in  adults 
and  al)Out  twenty-five  ])er  cent,  in  children  are  due  to  the  strcjjtococcus; 
seventv-five  per  cent,  of  the  cases  in  childhood  and  twenty-five  per  cent, 
in  adults  are  due  to  the  pneumococcus.  The  other  bacteria  found  in 
suppurative  ])leurisy  are  the  usual  pyogenic  organisms  to  which  refer- 
ence has  already  V)een  made.^ 

Suppurative   pericarditis  (pyopericardium  i    is   usually   the   result   of 

'  "Jour,  of  Path,  and  Bact,"  March,  IQ04.  p.  350.  and  July.  p.  365. 
'"Munch,  med.  Woch.,"  March  15,  1004.  p.  480. 

*  See  page  459. 

*  "Lancet,"  Aug.  17,  1901. 

*  "Arch.  f.  Kinderheilk.."  1904,  H(i.  xx.wi. 

*  "Boston  Med.  and  Surg.  Jour.,"  July  17,  1902,  p.  63. 
^See  p.  450- 


470 


SPECIAL   PATHOLOGY. 


pneumonia,  but  mav  be  associated  with  infection  of  any  contiguous 
structure,  particularly  the  pleura;  the  membrane  may  also  suffer  from 
infection  beginning  in  some  adjacent  abdominal  viscus.  Occasionally 
pericarditis  is  secondary  to  suppurative  lesions  of  the  myocardium  or 
endocardium,  or  due  to'  hematogenous  infection.  I  have  seen  it  follow 
ulcerative  lesions  of  the  esophagus  and  suppuration  of  a  contiguous 
lymph-node.  Batten  ^  observes  that  suppurative  pericarditis  is  seldom 
suspected,  rarelv  diagnosed,  hardly  ever  treated,  though  it  is  present  in 
three  per  cent,  of  all  dead  children;  the  accuracy  of  this  statement  can 
not  be  doubted,  and  my  experience  indicates  that,  so  far  as  recognition 
of  the  condition  is  concerned,  it  applies  to  adults  about  as  well  as  to 
infants. 

Suppurative  meningitis  may  result  from  hematogenous  infection,  the 
extension  of  suppurative  processes  from  the  skull  or  vertebra-,  and 
wounds  and  injuries  that  involve  the  bony  case  surrounding  the  brain 
and  cord.  Maragliano-  has  shown  that  infection  may  occur  from  the 
nasal  and  frontal  sinuses.  The  condition  frequently  is  associated  with 
middle-ear  disease. 

Suppurative  arthritis,  thecitis,  and  bursitis  usually  result  from  in- 
fected wounds  or  bacteria  brought  by  the  blood-stream.  Joints  are 
frequentlv  infected  from  the  adjacent  bone. 

Morbid  Anatomy  of  Suppurative  Serositis. — There  has  been  consider- 
able discussion  as  to  whether  purulent  inflammations  of  the  serous 
membranes  were  preceded  by  the  occurrence  of  serofibrinous  exudates. 
My  own  belief  is  that  in  most  of  these  cases,  even  when  primarily  sup- 
purative, an  exudate  containing  serum  or  fibrin  is  practically  always 
formed;  Beattie's  studies  support  this  view,  and  certainly  at  autopsy 
suppurative  serositis  without  the  presence  of  distinct  fibrin-bearing 
areas  is  an  exception.  The  chief  anatomic  difference  between  the 
suppurative  inflammation  and  the  typical  serofibrinous  serositis  is  the 
enormous  number  of  polvmorphonuclear  leukocytes  present  in  the 
former.  Fluidification^*  of' the  exudate  and  accumulation  of  pus  cells 
progress  during  the  activity  of  the  infection.  Swelling  and,  in  chronic 
cases,  proliferative  changes  are  constantly  observed  in  the  subserosa. 
The  latter  processes,  with  attempted  organization  of  the  deeper  layers 
of  the  exudate,  result  in  the  formation  of  an  investing  stratum  of  sup- 
purating granulation  tissue  resting  upon  the  fibrous,  edematous,  and 
hyperemic  subserosa.  In  the  earlier  stages  before  the  fibrous  tissue 
formation  is  marked  this  structure  is  called  a  pyogenic  membrane.  Struc- 
turallv,  such  a  membrane  is  composed  of  cellular  elements  not  unlike 
those'found  in  the  wall  of  an  abscess  (p.  295);  later,  the  free  surface 
continues  to  be  rich  in  leukocvtes.  and  therefore  largely  cellular.  AVithm 
this  cellular  accumulation  the  conflict  between  the  bacteria  and  the 
cells  continues,  and  is  manifested  by  the  associated  phagocytosis, 
necrosis,  and  pus-formation.  Below  this  w^all  there  is  sooner  or  later 
developed  a  layer  of  fibrous  tissue.  As  this  cicatricial  structure,  in 
conjunction  with  its  overlying  cellular  layer,  presents  a  certain  resist- 
ance to  the  further  invasion  of  the  underlying  tissues  by  the  bacteria, 

1  "Brit.  Med.  Jour.,"  Sept.  7,  1901. 

2  "Gaz.  osped  et  Clin.,"  1905,  No.  19. 

3  The  processes  operative  in  the  Hquefaction  of  inflammatory  exudates  and 
the  formation  of  pus  will  be  found  discussed  on  p.  294. 


SEROUS   MEMBRANES.  47I 

Park  jiroposed  for  it  the  name  prophylactic  membrane .  The  thickening 
mav  exceed  one  centimeter;  the  membrane  is  usually  touj^h,  the  sur- 
face soft  and  downy,  and  bleeds  uj)on  the  slij^htest  injury.  The 
deeper  layer  not  infrequently  contains  calcareous  material.  In  the 
suppurative  inflammatiun  of  serous  membranes  the  fever-producing 
element  present  in  the  noninfective  forms  has  its  activity  augmented 
bv  the  addition  of  the  pyrogenous  products  of  the  pyococci. 

The  changes  in  the  tissues  contiguous  to  the  sujjpurating  serosa 
resemble  those  already  described  as  occurring  in  the  nonsuppurative 
fonns  of  serositis.  In  the  peritoneum  the  intestines  dilate,  the  adja- 
cent muscle  degenerates,  the  lymphatics  contain  nvimerous  leukocytes, 
and  even  the  solar  plexus  shows  alterations  attributable  to  contact 
with  the  bacterial  toxins.  The  absorbed  poisons  produce  an  intense 
toxemia  which  usually  terminates  in  death.  When  the  lesion  is  local- 
ized in  the  vicinity  of  the  appendix,  uterus,  or  other  viscus,  the  ab- 
sorbing surface  is  proportionately  reduced,  and  the  outlook  is  more 
hopeful.  Such  localized  collections  of  pus  may  rupture  into  the  gen- 
eral cavity  and,  by  suddenly  inundating  the  serosa,  give  rise  to  a  violent 
toxemia  and  rapidly  fatal  general  peritonitis;  the  dangers  are  essen- 
tiallv  the  same  as  if  two  or  three  hundred  cubic  centimeters  of  pus 
were  injected  into  a  normal  peritoneum. 

Em]nema,  in  addition  to  the  mechanical  compression  of  the  lung, 
endangers  contiguous  structures  by  the  extension  of  the  infectious 
process.  A  suppurative  lymphangitis  may  traverse  the  lung,  giving 
rise  to  irregular  lines  of  purulent  inflammation  passing  from  the  per- 
ipherv  to  the  hilum;  a  bronchus  may  be  penetrated  and  the  patient 
drowned  in  the  pus,  or  the  infectious  matter  disseminated  in  the  opposite 
lung.  Extension  to  the  pericardium  is  not  rare.  The  changes  in 
the  muscles  and  diaphragm  are  essentially  similar  to.  but  more  marked 
than,  those  described  on  page  463  and  shown  in  Fig.  143,  page  251. 
and  Figs.  234  and  235.  Protracted  suppuration  of  the  pleura  induces 
irreparable  damage  in  the  underlying  lung,  subjects  the  patient  to  the 
dangers  of  general  sepsis  and  amyloid  disease,  and.  should  recovery 
ensue,  the  chest  is  frequently  deformed  and  the  spinal  column  may 
be  bent,  as  a  result  of  the  thoracic  wall  sinking  on  the  lung,  which  can 
not  expand.  Collapse  of  the  chest  wall  is  the  only  way  that  the  empyema 
cavitv  can  be  obliterated.  Sometimes  the  empyema  is  loculated;  the 
pus  cavitv  may  be  between  the  lobes  {interlobar  empyema),  or  at  the 
l)ase.  the  floor  of  the  purulent  collection  being  formed  by  the  diaphragm. 
These  cases  often  come  to  autopsy  without  the  nature  of  the  process 
having  been  suspected. 

Putrid  pleurisies  are  due  to  the  presence  of  saprophytic  l)acteria 
in  the  pus  of  empyema.  Guillemot.  Halle  and  Rist'  have  shown  that 
the  infection  is  practically  always  polymicrobic  and  that  anaerobic 
bacteria  are  almost  constantly  present.  The  toxic  processes  accom- 
panying such  conditions  are  usually  marked  and  reparative  activity 
suppressed.  In  resistant  individuals  the  infection  often  drags  on  for 
months  or  even  years ;    the  weakly  succumb. 

Suppurative  pericarditis  (pyopericardium)  offers  the  same  dangers  to 
the  heart  as  serofibrinous  mtlammation  and  exmlates.  and.  in  addition, 
two  important  possibilities.     The  toxic  processes  are  much  more  in- 
tense,   and.    secondly,    the   myocardial    alterations    are    more    marked. 
'  "Arch,  de  Mdd.  exper.,"  Sept.,  1904.  p.  571. 


472 


SPECIAL  PATHOLOGY. 


The  contiguous  layer  of  the  heart  muscle  often  manifests  advanced 
degeneration,  and  occasionally  pus  cells  may  be  seen  intercalated  be- 
tween the  fibers.  Rarely  mediastinal  abscess  follows  pericardial  suppura- 
tion; the  reverse  is  more  frequent.  Suppurative  pericarditis  seems 
more  prone  to  calcific  changes  than  suppurative  pleurisy  or  peritonitis. 
Inflamxmation  of  the  serous  membranes  is  sometimes  accompanied 
b}'  exudates  that  contain  blood;  to  this  condition  the  term  hemorrhagic 
inflammation  is  applied.  Hemorrhagic  serositis  occurs  most  commonly 
in  connection  with  debilitating  conditions,  such  as  tuberculosis,  asthenic 
states,  cancer  of  the  serous  membrane,  and,  rarely,  without  any  apparent 
cause.  Trauma  may  lead  to  hemorrhage  in  the  exudate.  Tapping 
may  rupture  some  of  the  delicate  vessels  of  an  organizing  exudate,  or 

withdrawal  of  the  serous 
exudate  may  remove  the 
support  to  the  delicate 
newly  formed  capil- 
laries, which  rupture, 
and  thereby  give  rise  to 
blood  in  the  fluid.  The 
hemorrhagic  phenom- 
enon may  show  in  the 
serum,  or  it  may  be  man- 
ifested by  petechias  or 
areas  of  subserous 
rhexis.  The  hemorrhagic 
inflammations  are  most 
frequent  in  childhood, 
although  not  unknown 
at  any  age.  The  pleura 
is  oftenest  affected.  The 
frequency  of  the  hem- 
orrhagic form  of  pleurisy 
is  variously  given  by 
different  writers:  Lewin 
found  the  effusion  hem- 
orrhagic in  4  out  of  50 
cases ;  Reimer,  five  times 
in  121  autopsies;  and 
Israel,^  twice  in  206. 

In  certain  forms   of 
chronic    serositis^   there 
occurs  an  inflammation,  of  a  low  order,  characterized  by  a  serous  exudate 

1  "  Jahrbuch  fiir  Kinderheilkunde,"  1898,  Bd.  xlvii,  No.  16. 

2  The  literature  of  chronic  inflammation  of  the  serous  membranes  will  be  found 
in  or  mav  be  traced  from  the  following:  Nicholls,  see  foot-note,  p.  461.  Harris, 
"Indurative  Mediastino-pericarditis,"  London,  1895.  Turk,  "Wien.  klin.  Woch.," 
XVI  Jahrgang,  Nos.  37,  39.  and  40.  Eichhorst,  "Deut.  med.  Woch.,"  April  17, 
1902.  Kelly,  "Amer.  Tour,  of  Med.  Sci.,"  Jan.,  1903,  p.  116.  Gibson,  BuUmore 
and  Conder,  "The  Practitioner,"  Feb.,  1Q03,  p.  213.  W.  Hale  White,  "Brit.  Med. 
Jour.,"  March  7,  1903,  p.  536.  Pollard,  "Lancet,"  March  28,  1903,  P-  871.  Brauer. 
thirty-second  German  Surgical  Congress,  June  3  to  6,  1903.  Schupfer,  "  Rif.  Med.," 
March  2,  1904.  Wetherill,  "Jour.  Amer.  Med.  Assoc,"  March  5,  1904,  p.  634- 
Scott,  "Amer.  Jour,  of  Obstetrics,"  Nov.,  1904.  Mouisset  and  Vallas,  "Lyon 
Med.,"  Feb.  5,  1905. 


Intestine.     Chronic  Adhesive  Peritonitis. 


SEROUS   MKMH RANKS.  473 

containing  but  few  cells  and  a  small  quantity  of  fiLrin.  This  type  of  in- 
flammation should  1)0  called  chronic  serous  exudative  serositis.  The  path- 
ologic ]irocess  is  due  to  ])ersisting  slight  irrilalioii  ainl  is  seen  in  the  joints 
as  a  result  of  loose  cartilages;  sometimes  it  follows  minor  injuries  of  the 
tendon-sheaths  and  bursa'.  A  similar  condition  is  occasionally  observed 
in  the  peritoneum,  pleura,  and  pericardium,  and  it  is  probable  that  some 
cases  are  tuberculous.  Benign  tumors  of  the  uterus,  ovary,  or  other 
abdominal  viscus  may  be  attended  by  such  a  process.  To  the  unaided 
eye  the  serous  membrane  frequently  shows  no  gross  lesion;  there  may 
be,  at  points,  whitish  or  slightly  opaque  areas,  particularly  if  the  serosa  has 
been  subjected  to  friction. 

Long-continued  inflammation  of  the  serous  membrane,  attended 
by  the  production  of  fibrin  and  serum — chronic  serofibrinous  exudative 
serositis — is  rarelv  observed;  sometimes,  however,  infcctinn  by  organ- 
isms or  slight  virulence  may  give  rise  to  such  a  ])rocess.  By  some  ob- 
servers the  later  stages  of  suppurative  inflammation  (p.  470)  of  the 
serous  membrane,  characterized  by  the  production  of  a  large  amount  of 
flbrinous  exudate  and  pus,  are  included  under  the  term  chronic  suppura- 
tive pleurisy,  pericarditis,  peritonitis,  etc. 

Chronic  hyperplastic  or  productive  inflammation  of  the  serous  mem- 
branes, also  called  progressive  hyaloserositis,  is  attended  In'  but  little 
exudate,  often  none,  and  is  characterized  by  the  production  of  a  large 
amount  of  flV)rous  tissue  which  forms  a  distinct  layer,  sometimes  i  cm. 
to  2  cm.  thick;  the  process  may  be  patchy  or  diffuse.  The  amount  of 
serum  present  in  these  cases  is  usually  small.  In  some  instances  the 
tendency  to  adhesion  is  slight,  while  in  others  large  areas,  and  sometimes 
all  of  the  cavity,  may  be  obliterated  by  complete  fusion  of  the  parietal 
and  visceral  layers  of  the  affected  serosa.  W.  Hale  White  refers  to 
cases  in  which  it  is  possible  to  remove  the  abdominal  viscera  intact,  as 
a  single  mass,  transverse  section  of  which  discloses  the  intestine  held 
open  by  the  thickened  investing  peritoneum.  The  liver  and  spleen  are 
sometimes  adherent  to  the  abdominal  wall  and  tmiformly  invested  in 
a  dense  white  layer  of  hyalofibrous  tissue.  In  other  cases  adhesions 
are  absent;  the  affected  serosa  is  covered  by  a  white  or  grayish-white 
fibrous  tissue  2  mm.  to  5  mm.  in  thickness  and  sometimes  thicker;  an 
organ  may  be  completely  invested  in  such  hyaloflbrous  tissue,  render- 
ing the  surface  white  or  grayish-white,  often  resembling  an  iced  cake — 
the  "Zuckergussleber"  of  the  German  writers. 

Often  the  peritoneum,  pericardium,  and  pleurse  are  affected,  hence 
the  name  multiy)le  or  polyserositis.  When  the  condition  is  restricted 
to  one  organ  (spleen  or  liver),  the  term  fibrous  capsulitis  is  sometimes 
applied,  although  it  is  questionable  whether  true  caj)sular  inflammation 
is  really  a  manifestation  of  this  process.  Histologically  the  thickene<l 
membrane  possesses  the  structural  characters  of  a  chronic  progressing 
inflammation.  The  new  tissue  is  composed  of  lamellae  of  hyaline  fibrous 
tissue  interspersed  with  formative  cells  in  various  stages  of  fibroblastic 
transformation;  often  the  capsule  of  the  organ  may  be  distinguished 
from  the  new  tissue  on  the  surface,  the  latter  appearing  as  an  organized, 
superimposed  stratum  on  a  slightly  altered  capsule.  The  blood-vessels 
of  the  newly  formeil  tissue  are  often  surrounded  by  mantles  of  cells 
indistinguishable  from  small  mononuclear  leukocytes.  The  condition 
may  or  may  not  be  associated  with  fibrous  hvj)erjilasia  of  the  interstitial 


474 


SPECIAL  PATHOLOGY 


tissue  in  the  enveloijed  organ.     There  is  no  necessary  relation  between 
the  two. 

With  regard  to  the  cause  of  the  condition  we  are  almost  totally 

ignorant.      The    ana- 
A  tomic     changes     and 

certain  of  the  clinical 
phenomena  indicate 
that  the  process  de- 
pends upon  the  pro- 
longed action  of  some 
irritant  the  nature  of 
which  is  unknown.  I 
am  strongly  inclined 
to  agree  with  Nicholls, 
who  is  almost  per- 
suaded that  the  pro- 
cess is  bacterial  in 
origin.  In  some  re- 
spects it  resembles 
the  chronic  produc- 
tive form  of  tubercu- 
losis, and  it  is  not  im- 
possible that  some 
cases  are  due  to  the 
tubercle  bacillus.  The 
absence  of  anatomic 
tubercles,  giant  cells, 
and  even  inability  to 
demonstrate  bacilli, 
do  not  necessarily 
constitute  conclusive 
proof  of  its  nontu- 
berculous  nature.  It 
is  possible  that  the 
chronic  productive 
serositis  without  ad- 
hesions may  be  differ- 
ent from  the  adhesive 
form,  but  the  reasons 
for  recognizing  them 
as  distinct  processes 
do  not  appear  con- 
vincing. 

Strongly  resem- 
bling the  foregoing 
are  pericardiomedias- 
tinitis, or  mediastino- 
pericarditis,  and  peri- 
carditis externa,  which 
are  closely  allied,  if 
not  identical  conditions.  The  names  given  are  applied  to  processes 
characterized   by    a    chronic   indurative   inflammation    extending   from 


Fig.  239. — Lung.  Chronic  Lnterstitial  Pneumonia,  Bronchiectasis, 
Hyaloserositis,  and  a  Terminal  Catarrhal  Pneumonia  Due  to 
Mixed  Lnfection  by  the  Tubercle  Bacillus  and  Pneumococcus. 

A  ,  A.  Greatly  thickened  pleura.  B.  Dilated  bronchi.  C.  One  of  many 
broad  strata  of  fibrous  tissue  irregularly  traversing  the  organ.  D.  Large 
caseous  lymph-node  near  hilum  of  lung  and  immediately  adjacent  to  the 
aorta,  a  section  of  which  is  shown  just  above.  The  aorta  is  the  seat  of 
slight   atheroma. 


SEROrS   MKMBKANKS.  475 

the  pericardium  into  the  mediastinal  tissues,  which  often  become  firm 
and  resisting  and  closely  attached  to  the  sternum  and  costal  cartilages. 
The  condition  may  or  may  not  be  associated  with  the  ordinary  form  of 
ptTK-arditis.  whicli.  for  purposes  of  distinction,  is  calle<l  pericarditis  in- 
terna. When  an  inrtammation  of  a  serous  membrane  terminates  in  acl- 
hesions  which  firmly  unite  the  apj)osed  serous  surfaces,  the  process  is 
sometimes  called  obliterative.  and  hence  it  is  possible  to  speak  of  ob- 
literative  ])leurisy.  obliterative  pericarditis,  obliterative  peritonitis,  etc.; 
such  manifestations  are  also  called  chronic  adhesive  inflammations. 

In  addition  to  the  foregoing  forms  of  chronic  pericarditis,  it  is  neces- 
sary to  recognize  certain  lesions  which  are  the  results  of  past  acute  in- 
flammatorv  conditions;  by  some  these  are  grouped  with  the  chronic 
inflammations.  In  some  cases  it  is  evident  that  the  inflammation  began 
with  an  acute  process  which  continued,  and  at  the  time  of  examination 
had  lost  all  of  its  acute  characters,  but  is  continuing  as  a  chronic  lesion. 
This  tvpe  belongs  with  the  chronic  forms  described  above.  In  other 
cases  the  process  has  long  ceased  to  be  active,  there  is  no  evidence  of 
progression,  the  alterations  remaining  exactly  as  they  were  left  when 
the  active  stages  of  the  acute  process  subsided.  The  condition  present 
mav  be  that  of:  (i)  Partial  or  complete  adhesion;  (2)  large  masses  of 
fibrin  whipped  off  in  the  serum  may  not  have  undergone  absorption, 
but  sometimes  are  perpetuated  as  caseous  or  semisolid  collections 
too  large  to  be  vascularized;  (3)  caseous  areas  resulting  from  the 
absorption  of  the  fluid  portion  of  a  past  pus  collection  or  from  tubercu- 
losis of  the  membrane:  (4)  calcareous  masses  in  the  newly  formed  in- 
flammatorv  tissues. 

Tuberculosis  of  the  serous  membranes,'  like  tuberculosis  elsewhere, 
is  manifested  by  the  occurrence  of  many  lesions,  some  of  which  bear 
no  resemblance  to  the  others.  It  may  be  acute  or  chronic.  The  source 
of  the  infection  is  usually  some  organ  covered  by  the  serosa  or  some 
contiguous  structure  from  wdiich  the  bacilli  reach  the  membrane.  In 
the  peritoneum,  tuberculosis  of  the  intestine,  lymph-nodes,  uterus  or 
its  appendages,  or  the  abdominal  wall  (including  the  vertebrae)  may  in- 
fect the  serosa.  The  cases  of  alleged  primary  tul)erculosis  of  the 
peritoneum  must  be  regarded  with  suspicion.  According  to  Bottomley.- 
Borschke  obser\-ed  primary  infection  once  in  226.  and  Munsterman 
once  in  46  cases.  An  acute  miliary  tuberculosis  of  the  peritoneum  may 
result  from  a  hematogenous  dissemination  of  the  bacillus,  and  occa- 
sionallv  the  peritoneum  is  infected  from  the  thoracic  serosae.  Tuber- 
culosis of  the  pleura  is  usually  due  to  infection  from  the  underlying  lung, 
although  it  has  been  suggested  that  the  bacteria  may  enter  the  apex  from 
the  cervical  Ivmph-nodes.  the  latter  infected  by  way  of  the  tonsils  and 
pharynx.     Tuberculous  pleurisy  secondary  to  mediastinal,  esophageal, 

'  MacCallum,  •'Bull,  of  Johns  Hopkins  Hosp.."  igoi.  W.  Hale  White,  "Clin- 
ical Tour  ■'  Aug.  21.  1901."  Xicoloff,  These  de  Paris.  1Q04.  Thayer.  "Bull,  of 
lohns  Hopkins  Hosp.."  Mav.  1904.  p.  149.  Scagliosi.  "Deut.  med.  Woch..'' June 
0  1904.  Xorris,  "Univ.  of  Penna.  Med.  Bull.."  July-August.  1904.  Ipscn. 
"Virchow's  Arch.."  Sept.  i.  1904.  Bd.  177.  p.  "^/O.  LonK>-ear.  "Amer.  Jour,  of 
Obstetrics.  '  Nov..  1904.  Roscnbach.  Nothnagcl's  Encyclopedia.  American  edition. 
"  Diseases' of  the  Bronchi.  Pleura,  and  Lunjjs."  190.^  p.  962.  Cornet.  Nothnagcl's 
Encyclopedia.  American  edition,  "Tuberculosis,  Acute  and  Chronic  Miliary  Tu- 
berculosis." 1004,  p.  195.  . 

'  •  Med.  and  Surg.  Reports  of  the  Boston  City  Hospital,     1900.  eleventh  series. 


476  SPECIAL   PATHOLOGY. 

and  vertebral  lesions  is  less  common.  This  statement  is  made  with  the 
understanding  that  infections  from  the  peribronchial  lymph-nodes  be- 
long with  those  due  to  extension  from  the  lung  and  not  with  those 
arising  from  the  mediastinum.  Hematogenous  infection  of  the  pleura 
occasionally  occurs. 

Tuberculous  pericarditis  is  rarely,  if  ever,  primary;  usually  the 
infection  is  an  extension  from  tuberculosis  of  contiguous  structures, 
especially  the  lymph-nodes  near  the  base  of  the  heart.  The  pericardium 
may  also  be  affected  from  the  pleura,  adherent  lung,  mediastinal  tis- 
sues, esophagus,  and  peritoneum.  In  a  large  percentage  of  cases  peri- 
carditis is  due  to  hematogenous  infection.  Sometimes  the  lesion  is 
a  part  of  an  acute  general  miliary  tuberculosis.  The  last  statement 
also  applies  to  tuberculosis  of  the  meninges.  Meningeal  infection 
may  occur  from  contiguous  structures,  such  as  the  bodies  of  the  verte- 
brae, middle  ear,  or  other  foci  in  the  bony  walls  enclosing  the  brain  and 
cord.  Tuberculous  thecitis  may  be  due  to  inoculation,  but,  in  the  large 
majority  of  cases,  is  an  infection  from  the  blood.  The  same  is  true  of 
bursitis'  due  to  the  tubercle  bacillus.  In  the  joints,  tuberculosis  is 
commonly  the  result  of  extension  from  contiguous  bone.  There  can 
be  no  doubt  that  in  all  these  cases  colonization  of  the  tubercle  bacillus 
is  favored  by  trauma  or  any  other  antecedent  condition  which  weakens 
the  resistance  of  the  tissues. 

Morbid  Anatomy  of  Tuberculosis  of  the  Serous  Membranes. — It  is 
possible  to  recognize  acute  and  chronic  types  of  the  affection;  the 
former  will  be  considered  first.  An  eruption  of  tubercles  in  a  serous 
membrane  may  be  attended  by  the  accumulation  of  a  clear  serum  in  the 
cavity  and  no  recognizable  fibrinous  deposit  on  the  surface  of  the  mem- 
brane. In  such  cases  the  tubercles  appear  to  be  in  the  subserosa,  and 
usually  are  easily  recognized  as  grayish-white  dotlets  scarcely  a  milli- 
meter'in  diameter;  as  a  rule,  they  are  palpable.  These  are  the  cases 
which,  when  the  peritoneum  is  involved,  appear  to  be  greatly  benefited  by 
operative  procedure.  In  other  cases  of  tuberculous  serositis  the  affected 
membrane  is  covered  by  a  shaggy  coat  of  fibrin  indistinguishable  from 
that  seen  in  the  ordinary  type  of  acute  serofibrinous  pleurisy  or  peri- 
carditis. Norris  found  this  form  in  seven  of  the  eighty-two  cases  of 
pericarditis  which  he  studied.  The  quantity  of  fluid  is  often  excessive; 
the  peritoneum  may  contain  four  to  eight  liters,  and  the  pleura  half 
as  much;  Hirtz  reported  a  case  in  which  2700  c.c.  of  blood-stained  serum 
was  present  in  the  pericardium.  Sometimes  the  effusion  is  hemor- 
rhagic and  distinctly  fibrinopurulent  exudates  are  occasionally  en- 
countered. 

The  chronic  forms  of  tuberculous  serositis  may  be  sequences  of  the 
acute,  but  often  arise  insidiously.  A  chronic  serous  inflammation,  or 
at  least  a  chronic  inflammation  of  the  serosa  with  an  abundant,  clear, 
straw-colored,  serous  exudate,  occurs  particularly  in  the  peritoneum; 
many  patients  recover  from  this  form.  In  another  type  of  the  affection 
the  structural  changes  resemble  those  of  a  chronic  productive  adhesive 
serositis.  Multiple  adhesions  form,  or,  in  some  cases,  the  cavity  of 
the  affected  serosa  may  be  obliterated  by  firmly  organized  fibrous  tissue 
in  which  but  few  tubercles  and  no  caseous  areas  can  be  demonstrated. 
Ipsen  has  been  able  to  collect  twelve  cases  of  tuberculosis  in  man  possess- 
ing the  anatomic  characters  of  the  bovine  form  of  the  affection.     In 


SEROUS   MEMBRANES.  477 

some  of  these  instances  the  lesions  on  the  serosa*  resemble  the  changes 
seen  in  cattle,  which  consist  of  nodular  masses  of  fibrous  tissue  with 
little  or  no  tendency  toward  caseation.  The  pedunculated  and  sessile 
nodules  described  by  MacCallum  resemble  this  type.  In  still  another 
tjroup  of  tuberculoses  large  nodules  with  caseous  centers  and  fibrous 
peripheries  are  irregularly  distributed  over  the  affected  serosa.  In 
the  case  of  tuberculous  mediastino-pericarditis  reported  by  Ellis'  the 
mediastinal  tissues,  pericardium,  and  heart  were  fused  in  a  single  mass, 
and  large,  caseous  nodules  surrounded  the  bronchi,  trachea,  and  large 
vessels.  The  cavities  of  both  pleura*  were  obliterated.  The  caseous 
nodules  varied  in  diameter  from  0.2  cm.  to  2  cm.,  and  at  points  the 
tuberculous  ])rocess  involved  the  myocardium.  It  is  interesting  to 
note  that  in  this  case  the  examination  of  a  large  number  of  sections 
failed   to  .1i<>-'<>^e  a  single  characteristic  tubercle  or  even  a  giant  cell; 


^  .^A-v- 


:-•  Ol: 


-  f^  ^^^?  "'-^'^^->  ^'fi^^'   ''^^'  :  "'^i^  ?r>^^^ 


Fig.  240.— .\ciTE  TUBERCULOUS  Pericarditis.  Vertical  Section  of  Inflammatory  E.xudate. — (Schmaus.) 

X  250  diameters. 
a.  Subpcricardial  fat.     b.  I.ayer  of  granulation  tissue  that  extends  to  the  layer  of  fibrin,  d.     c.  c.  TubercJes  contain- 
inK  If i.mi -cells.     Other  tubercles  are  shown,  in  some  of  which  degenerative  changes  arc  iK-ginning  to  evince 

ihemsi-Jvfs. 

the  new  tissue  consisted  of  lymphoid  and  fibrous  structures  in  which 
caseation  had  run  riot.  Tubercle  bacilli,  however,  could  be  demon- 
strated. 

Cytodiagnosis  offers  aid  in  determining  the  character  and  origin 
of  exudates  m  the  serous  cavities.     The  method  is  discussed  on  p.  291. 

Actinomycotic  serositis  has  been  reported,  but  the  condition  is 
rare;  it  is  usually  secondary  to  actinomycosis  of  some  viscus  covered 
bv  the  peritoneum  or  pleura.  The  lesion  is  commonly  chronic  and  the 
fungus  mav  be  demonstrated  in  the  exudate  or  granulation  tissue. 
Actinomvcotic  pleurisy  is  usually  due  to  infection  from  the  underlying 
hmg;  the  same  is  true  of  the  pericardium;  less  frequently  the  latter 
structure  is  involved  secondarily  to  the  mediastinal  tissues.  Actino- 
'  "Proceed,  of  Path.  Soc.  of  Phila.,"Jan.  2q.  IQ04. 


478 


SPECIAL   PATHOLOGY. 


myeotic  lesions  of  the  serous  membranes   are  often  strictly  localized 
to  the  area  in  which  infection  occurred. 

Various   serous  membrane   inflammations   have  been   attributed   to 
syphilis,  and  in  the  meninges  the  chronic  productive  meningo-encepha- 


FiG.  241. — Chronic,  Adhesive,  Ixdlrative,  and  Caseous  Tuberculous  Mediastixopericarditis.  Heart 
AND  Adjacent  Mediastinal  Structures.     (Four-ninths  natural  size.) 

A.  Trachea  slightly  distorted  by  pressure.  B.  Left  bronchus,  compressed  by  enlarged  peribronchial  lymph- 
nodes.  C.  Aorta;  the  arch  is  displaced  to  the  right,  the  middle  of  the  arch  is  elongated  largely  at  the  expense 
of  the  descending  portion.  It  is  probable  that  a  large  part,  but  certainly  not  all,  of  this  distortion  is  postmortem. 
D.  One  of  several  caseous  nodes  on  the  mediastinal  aspect  of  the  pericardium;  some  of  these  mxlules  are  in- 
distinguishable from  caseous  masses  that  have  arisen  in  the  pericardial  synechia.  £.  Area  of  caseous  tubercu- 
losis, occupying  fissure  between  the  left  auricle  and  corresponding  ventricle.  F.  Caseous  mediastinal  (peri- 
tracheal) lymph-nodes.  G.  Thickened  and  adherent  parietal  layer  of  the  pericardium.  H.  Thickened 
visceral  layer  of  the  pericardium  (epicardium).  The  space  between  F  and  G  is  occupied  by  tirm,  grayish, 
slightly  hyaline  fibrous  tissue  in  which  are  embedded  many  caseous  areas.  /.  Caseous  mass  e.xtending  into 
the  myocardium.  Even  in  this  short  incision,  through  the  lateral  wall  of  the  left  ventricle,  several  points 
of  myocardial  invasion  can  be  seen. 


litis  is  clearly  of  syphilitic  origin.^     Eruptions  of  leprous  nodules  may 
occur  on  the  pleura  and  are  usually  secondary  to  pulmonary  infection. 
Air  in  the  serous  cavities  is  always  regarded  as  a  source  of  danger 
'  See  Diseases  of  the  Nervous  System. 


SEROUS   MEMBRANES.  479 


and  is  usually  followed  l»y  evidences  of  infection.  It  was  once  believed 
that  air  was  an  irritant  capaV^le  of  producing'  inflammation.  Clinical 
and  experimental  evidence  shows  that  sterile  air  j^nves  rise  to  no  struc- 
tural alteration  in  the  serosa,  although  the  viscera  (especially  the  lung) 
may  he  profoundly  influenced  by  the  pressure  induced  by  the  gas. 
Lundie'  reported  an  instance  where  air  was  present  in  the  pleura  and 
pericardium  on  at  least  two  occasions  and  at  no  time  was  there  any 
evidence  of  inflammation.  Air  is  often  introduced  into  the  serous 
cavities  for  diagnostic  or  therajieutic  purposes,  and  if  sterile,  does  no 
harm.  Gas,  present  in  most  instances,  is  the  result  of  wounds  admitting 
air  from  the  outside,  or  traumatic  ruptures  or  penetration  of  some  hollow 
viscus;  in  either  case  the  gas  is  accompanied  by  infection  which  rapidly 
produces  inflammation  that  is  usually  suppurative.  In  some  cases 
ulceration,  gangrene,  or  other  pathologic  processes  perforate  the  serous 
covering  of  a  hollow  viscus,  admit  air  and  infection,  and  give  rise  to 
serositis.  Gas  may  arise  in  the  serous  cavities  as  a  result  of  infection 
by  aerogenic  bacteria.  The  organisms  present  are  usually  the 
Bacillus  aerogenes  capsulatus  or  other  gas-producing  bacteria,  and  in 
some  cases  the  colon  bacillus  alone.  May  and  Gebhardt^  suggest  for 
this  tvpe  the  name  zymotic  peritonitis,  pneumothorax,  or  pneumoperi- 
cardium. This  form  is  occasionally  seen  m  the  ])eritoneum.  but  most 
of  the  peritonitides  associated  with  the  presence  of  air  are  due  to  per- 
foration of  the  stomach  or  intestine.  Most  of  the  cases  of  pneumo- 
thorax are  the  result  of  tuberculosis  of  the  lung.  Biach  found  that 
of  918  cases  of  pneumothorax,  715  were  due  to  tuberculosis,  65  were 
associated  with  gangrene  of  the  lung,  45  accompanied  empyema,  and 
32  followed  trauma.  Fussell  and  Riesman'  were  abL^  to  collect  56 
cases  thought  not  to  be  tuberculous;  many  of  these  ifollowed  trauma. 
Bovaird^  reported  2  cases  of  pneumothorax  resulting  from  rupture 
of  areas  of  bronchopneumonic  consolidation.  T\vo  others  were  due 
to  ruptured  abscess  and  the  fifth  was  supposeO  to  have  resulted  from 
the  bursting  of  an  emphysematous  bleb.  Tlte  condition  sometimes 
follows  violent  respiratory  effort,  as  coughing,  particularly  in  per- 
tussis."^ 

Pneumopericardium  is  almost  always  the  result  of  penetration  of  the 
sac  from  without.  (Jf  the  38  cases  collected  by  James,«  4  were  thought 
to  be  due  to  infection  by  gas-forming  bacilli;  in  7  the  perforation  was 
in  the  esophagus  and  in  two  gastric  ulcer  penetrated  the  pericardium. 
In  the  case  reported  by  MuUer  pyopericardium  {)erforated  the  lung.  In 
most  cases  infection  accompanies  the  entering  air.  and  pneumopericar- 
dium is  converted  into  a  pyopneumopericardium. 

Hemopericardium,  hemothorax,  and  hemoperitoneum  are  usually  due 
to  trauma,  particularly  crushes  and  penetrating  wounds  of  the  cavities. 
The  condition  may  also  result  from  ruptured  aneurysm,  and  a  variable 

'"Edinburgh  Med.   Jour.."  iSqi,  No.   1805. 
»  "Deut.  Arch.  f.  klin.  Med."  Ixi. 

*  "Amer.  Jour,  of  Med.  Sci.,"  Aug..  1902,  p.  218. 
*"Arch.  of  Pediatrics."  Nov.,  IQ03. 

*  For   fuller  literature   concerning   pneumothorax   consult    Edmunds.       Hru 
Med.  Jour,"  Nov.  21.  1003,  p.  1322.     Wel)er,  "Zeit.  f.  TuV)erk.  u.  Heilstw.."  vol. 
iv.   No.  6.      Trask,    •lour.   Amer.   Med.    Assoc."  March.  5.  1904.  p.  641.     Emer- 
son. "Johns  Hopkins  Hospital  Reports."  1903.  vol.  xi.  pp.  i  to  445. 

*  "Amer.  Med.."  July  2.  1904.  p.  23. 


480  SPECIAL  PATHOLOGY. 

quantity  of  blood  may  be  found  mixed  with  the  contained  serum  in 
scurvv,'  pernicious  anemia,  hemorrhagic  septicemias,  purpura,  phos- 
phorus poisoning,  leukemia,  and  allied  dyscrasias.  In  the  latter  group 
of  cases  petechiae,  and  subserous  hemorrhages  of  a  larger  size,  ai-e  usu- 
ally present. 

Tumors  of  the  serous  membranes  may  be  primary  or  secondary;  the 
former  may  be  benign  or  malignant.  Most  of  the  benign  tumors  are 
situated  in  the  omentum,  in  which  myxoma,  lipoma,  fibroma,  chon- 
droma, and  even  osteoma  may  occur.  Hellier^  reports  a  lymphangioma 
of  the  omentum  and  peritoneum  which  simulated  ovarian  tumor.  It  is 
probable  that  the  congenital  multilocular  cystoma  of  the  omentum  ob- 
served bv  Young,-  and  a  similar  case  reported  by  Hearn,=*  were  of  this 
tvpe.  Important  among  the  abdominal  tumors  are  the  retroperitoneal 
neoplasms^  and  cysts.  In  this  location,  myxoma,  lipoma,  and  sarcoma 
occur;  Steele  has  been  able  to  collect  ninety-six  cases  belonging  to  the  last 
group.  Aside  from  the  cysts  arising  from  the  solid  viscera  of  the  abdom- 
inal cavity,  (i)  serous,  (2)  blood,  (3)  chyle,  (4)  dermoid,  and  (5)  parasitic 
cysts  are  sometimes  observed.^  In  the  case  reported  by  Richardson  the 
cyst  contained  eight  pints  of  milky  fluid.  Liquid  accumulations  in  the 
lesser  omental  cavity  are  sometimes  called  pseudo-cysts  of  the  abdomen. 
Hydatids  are  the  most  common  of  the  parasitic  cysts,  although  cysti- 
cerci  are  also  observed. 

The  most  frequent  primary  tumor  of  the  serous  membrane  is  endo- 
thelioma." This  may  give  rise  to  distinct  nodules,  but  frequently  is  a 
diffuse,  flattened  growth  resembling  the  thickening  produced  by  chronic 
hyaloserositis.  The  pleura  is  usually  involved;  the  meninges  of  the 
brain  and  cord  are  second  in  point  of  frequency ;  the  tumor  is  not  com- 
mon in  the  pericardium  or  peritoneum;  it  sometimes  affects  the  burscC 
and  tendon-sheaths.  There  has  been  considerable  discussion  as  to 
whether  it  arose  from  the  surface  cells  of  the  serosa  or  from  the  endo- 
thelium of  the  lymph-vessels.  Histologically  the  structure  so  closely 
resembles  the  alveolar  types  of  cancer  that  many  of  these  neoplasms  are 
reported  as  instances  of  primary  carcinoma  of  the  serosa.  The  resem- 
blance of  the  process  to  chronic  inflammation  of  the  serous  membranes 
is  intensified  by  the  occurrence  of  exudates,  which  are  usually  hemor- 
rhagic, or  rapidly  become  so.  The  malignancy  in  different  cases  varies; 
sometimes  life  is  prolonged  for  years,  and  in  other  cases  the  condition 
terminates  fatally  in  a  few  months.  The  tendency  to  metastatic  de- 
posits is  usually  slight. 

The  secondary  tumors  of  'the  serous  membranes  may  be   carcinoma- 

'  "Brit.  Aled.  Jour.,"  Xov.  12,  1904,  1311. 

^  "Lancet,"  Jan.  21,  1905,  p.  157. 

'  "Annals  of  Stirgerv,"  1897. 

^Adami,  "Montreal  Med.  Jour.,"  1897,  vol.  xxv.  Douglas,  "Jour.  Amer. 
Med.  Assoc,"  March  26,  1898.  Steele,  "Amer.  Jour,  of  Med.  Sci.,"  March,  1900. 
and  June,  1904. 

*  For  literature  of  these  cvsts  see  Blum,  "Centralbl.  f.  d.  Granzgebieten  d. 
Med.  u.  Chir.,"  1902,  vol.  v.'  McMurtry,  "  N.  Y.  Med.  Jour.,"  Dec.  31,  1904, 
p.  1256.      Richardson,  "  Boston  Med.  and  Surg.  Jour.,"  Feb.  9,  1905,  p.  151. 

*  Scagliosi,  "Deut.  med.  Woch.,"  1904,  xxx,  1715,  No.  47.  Hilber,  "Jahrbuch. 
f.  Kinderheilk.,"  Bd.  59,  H.  3.  Bassoe,  "Trans,  of  Chicago  Path.  Soc,"  Nov.  9, 
1Q03,  p.  31.  Nager, '^"  Zieg.  Beitr.,"  1904,  xxxvi,  H.  i.  Unger,  "Wien.  klin. 
Woch.,"  Dec.  24,  1903,  p.  1457.  Bonheim,  "  Munch,  med.  Woch., "April  26,  1904, 
p.  741.     Adler,  "X.  Y.  Acad,  of  Medicine,"  Oct.  20,  1904. 


SEROUS   MEMBRANES.  48  1 

tous  or  sarcomatous,  and  arc  usually  the  result  of  extension  from  a 
neoplasm  of  some  viscus  within  the  aflected  cavity  or  in  the  wall  of  the 
latter.  In  some  cases  the  secondary  nodules  are  distributed  over  the  serosa 
as  minute  elevations  resemblinj;  warts;  this  condition  may  simultaneously 
afTcct  all  of  the  serous  cavities  of  the  trunk.  When  due  to  cancer,  it  is  called 
carcinosis,  and  when  the  new  growth  is  sarcoma,  the  term  sarcomatosis 
IS  applied.  Colloid  cancer  of  the  j)eritoneum  is  usually  secondary'  to  a 
primary  growth  in  the  alimentary  canal,  although  Parkinson'  and  others 
have  reported  instances  in  which  the  growth  was  primary.  In  Parkin- 
son's case  the  patient  was  twelve  years  old,  at  which  age  the  disease  is 
exceedingly  rare. 

'  "Soc.  for  the  Studv  of  Disease  in  Children,"  May  15,  1003. 


3^ 


CHAPTER  VI. 

VASCULAR    SYSTEM. 

HEART.' 

Normal  Structure. — The  heart  is  essentially  a  hollow  muscle  divided 
by  partitions  into  two  distinct  sides,  between  which,  normally,  there 
is  no  communication;  each  side  is  further  divided  by  a  perforated 
septum  into  two  cavities,  known  respectively  as  an  auricle  and  a  ven- 
tricle. The  opening  through  which  the  auricle  communicates  with  the 
ventricle  on  each  side,  called  the  auriculoventricular  opening  or  orifice, 
is  guarded  by  valves  that  open  toward  the  ventricle;  on  the  right  side 
the  valve  is  known  as  the  tricuspid,  on  the  left,  as  the  mitral.  The 
right  ventricle  communicates  with  the  pulmonary  arter}^  and  the  left 
ventricle  with  the  aorta,  the  two  orifices  being  guarded  by  valves  opening 
toward  the  vessels.  These  valves  are  each  composed  of  three  cusps, 
crescentic  or  semilunar  in  outline,  and  known  as  the  semilunar  valves 
of  the  pulmonary  artery  and  of  the  aorta  respectively.  The  exterior 
of  the  heart  is  covered  by  the  pericardium,  to  which  reference  has 
already  been  made  (serous  membranes,  p.  452);  the  interior  is  lined 
by  a  flattened  layer  of  connective-tissue  cells  (endocardium)  applied 
almost  directly  to  the  cardiac  fiber,  with  but  little,  if  any,  loose  con- 
nective tissue  intervening;  the  valves  are  composed  of  two  layers  of 
the  endocardium,  reinforced  by  fibrous  tissue,  in  which  are  a  few  elastic 
fibers.  The  valves  of  the  right  side,  having  less  work  than  those  of  the 
left,  are  much  the  thinner,  containing  relatively  less  fibrous  tissue. 
The  endocardium,  including  most  of  the  tissue  that  enters  into  the 
formation  of  the  valves,  is  nonvascular,  probably  receiving  its  nutrition 
from  the  blood  flowing  over  it.  The  cardiac  muscle  is  of  the  striped 
variety,  but  differs  from  voluntary  striped  muscle;  the  fibers  are  usually 
said  to  possess  no  sarcolemma,  and  they  inosculate  by  branched  fila- 
ments, passing  from  one  to  another;  there  is  no  bundling  of  the  fibers, 
and  the  individual  elements  are  smaller  than  those  of  the  purely  voluntary 
muscle.  Marceau^  has  shown  that  the  mammalian  heart  possesses  a 
higher,  and  more  complicated,  development  than  the  heart  of  some 
other  vertebrates.  Nourishment  for  the  organ  is  supplied  by  the 
coronary  arteries,  the  circulation  in  which  is  in  some  respects  peculiar. 
The  usual  teaching  that  these  are  terminal  vessels  is  not  correct,  although 
the  anastomosis  between  the  two  trunks  is  never  free;  in  some  hearts 
there  is  no  communication  between  the  branches  of  the  right  and  left 
coronary  arteries.  Galli-^  has  shown  that,  in  many  organs,  the  anasto- 
mosis is  present,  although  never  abundant.     Meigs*  believes  that  the 

'  For  method  of  removing  the  heart  and  completing  its  dissection  see  pp.  11 
and  12.  ^ 

^  "Ann.  So.  nat.  Serie  8  Zool.,"  vol.  xxix,  1903,  p.  199. 

^  "Miinch.  med.  Woch.,"  July  7,  1903,  p.  1146. 

^"Proceed,  of  the  Path.  Soc.  of  Phila.,"  1898,  p.  186;  references  to  earlier 
papers. 


VASCULAR   SYSTEM, 


483 


capillaries  actually  enter  the  muscle-fibers.  The  connective  tissue  of 
the  normal  myocanlium  is  scanty  and,  except  in  the  vessels,  the  amount 
of  elastica  is  so  small  as  to  be  scarcely  demonstrable. 

Size  of  Xormal  Heart. — The  heart  is  about  the  size  of  the  fist  of 
the  individual;  its  weight  in  the  male  varies  between  285  gm.  and 
450  gm.  (10  and  15  ounces),  with  a  mean  between  340  gm.  and  390 
gm.  (11  and  13  ounces).  The  heart  of  the  adult  female  weighs 
between  200  gm.  and  400  gm.  (7  and  13  ounces);  mean,  between  285 
gm.  and  300  gm.  (9  and  10  ounces).  The  taller  the  individual,  the 
heavier  the  heart.  In  forming  an  estimate  as  to  the  normal  weight 
of  the  heart,  the  size  of  the  body  and  the  amount  of  work  ref|uired 
of  the  organ  must  be  taken  into  consideration.  The  laborer  weigh- 
ing So  kilos  will  almost  certainly  possess  a  heart  weighing  more 
than  that  of  a  clerk  whose  body-weight  is  the  same.  The  relation 
between  the  cardiac  and  body-weights  is  not  sufHciently  constant  to 
afford  a  basis  for  a  positive  opinion  in  a  doubtful  case.  There  are  so 
many  factors  to  be  considered,  the  work,  the  nutrition,  the  age,  the 
height,  the  sex,  etc.,  that  no  arbitrary  rule  can  be  laid  down  to  fit  all 
conditions.  The  observer  must  weigh  all  obtainable  facts  and  for- 
mulate his  conclusion  afterward;  even  then  he  mav  be  in  doubt  in 
certain  cases.  The  left  ventricular  w'all  is  about  1.25  cm.  (^  of  an  inch) 
in  thickness,  the  right  about  0.4  cm.  (^  of  an  inch).  Measurement  alone 
affords  insufficient  evidence  upon  which  to  base  an  opinion  as  to  the 
presence  or  absence  of  hypertrophy;  the  wall  of  a  widely  distended, 
hypertrophied  heart  may  be  thinner  than  the  contracted  normal  myo- 
cardium. The  ventricular  wall  is  thickest  at  its  middle  and  thinnest 
at  the  apex. 


Diamp:ters 

OF    C 

ARDIAC 

Oi 

XIFICES.- 

-{After 

IIa»iiUo, 

n.) 

Male. 

Female. 

Greatest. 

I>east. 

A 

vcrage. 

Greatest. 

Least. 

Average 

Aortic . 

Mitral 

Pulmonary 
Tricuspid,. 

Artery,  . 

Inch 

'■5 

2    2 

Inch 
0.9 
I.I 
I.O 

1-3 

Inch 

1.0 

1-4 
1.2 

i.S 

Inch 
1.0 

1-3 
1-7 

Inch 
0.8 
1.0 
1.0 
14 

Inch 

0.0 

1.2 

I.I 

1-5 

The  taller  the  subject,  the  larger  the  orifices. 


MALPOSITION  OF  THE   HE.VRl. 

(a)  coxgexital. 

1.  Cervical  Heart. — Heart  in  the  neck;  the  condition  may  be  com- 
plete or  ]iartial.  and  is  more  frequent  in  the  lower  animals  than  in  man. 

2.  Abdominal  Heart. — Through  faulty  development  of  the  diaphragm 
the  heart  may  sink  into  the  abdominal  cavity;  usually  a  fetus  so  affected 
dies,  but  Holt's  patient  was  five  months  old  and  appeared  otherwise 
healthy.  Occasionally,  the  diaphragm  does  not  develop  immediatelv 
under  the  pericardium,  and  when  the  heart  does  not  sink  through  the 
opening,  an  abdominal  viscus  may  ascend  into  the  pericardium,  a  re- 
sult induced  by  the  difference  l)etween   the  pressures  within  the  two 


484 


SPECIAL  PATHOLOGY. 


cavities.  When  there  is  an  opening  in  the  diaphragm  and  any  of  the 
abdominal  viscera  enter  the  thoracic  cavity,  the  changed  relations  and 
altered  pressure  practically  always  force  the  heart  out  of  position.  As 
the  diaphragmatic  fenestrum,  through  which  such  a  hernia  may  occur, 
is  usually  on  the  left  side,  the  heart  is  displaced  toward  the  right;  such 
a  malposition  is  essentially  similar  to  acquired  ectopia  resulting  from 
diaphragmatic  hernia. 

3.  Pectoral  Heart. — The  heart  may  lie  anterior  to  the  chest-wall; 
the  wall  ma}"  be  absent,  or  it  may  have  partly  closed  behind  the  mis- 
placed heart;  in  rare  instances  there  may  be  no  pericardium,  and  less 
frequently  the  heart  is  extracorporeal, — /.  c,  outside  the  body, — the 
integument  having  partly  united  behind  it.     Such  conditions  are  not 

compatible  with  pro- 
longed extrauterine 
life,  and  are  usually 
associated  with  other 
iissural  malformation 
of  the  thoracic  and  ab- 
dominal walls. 

4,  Dexiocardia.^ — A 
heart  on  the  right  side 
is  compatible  with  life, 
and  is  recognized  by 
insurance  companies  as 
not  in  any  way,  of 
necessity,  increasing 
the  risk.  Vehsemeyer"- 
states  that  but  twenty 
cases  of  true  dexiocar- 
dia  have  been  reported. 
It  is  usually  associated 
with  transposition  of 
the  abdominal  viscera, 
the  liver  going  to  the 
left  side,  etc.,  the  com- 
bination of  transposed 
organs  being  known  as 
the  situs  inversus .^ 
This  condition  is  also 
called  transposition,  inversion,  lateral  inversion  of  the  viscera,  hetero- 


FiG.  242. — Pector.\l  Heart. 
The  chest  wall  has  partly  closed  behind  the  misplaced  organ,  which  is  con- 
nected with  the  interior  of  the  body  by  a  pedicle  composed  of  the 
large  vessels.     The  chUd  lived  twenty-three  and  a  half  hours.     (The 
illustration  is  from  a  photograph.) 


1  "Deut.  med.  Woch.,"  March  iS,  1897.  See  also  Gamier,  "La  Presse  Med.," 
July  12,  1899,  p.  15.  Magnan,  Perpere  and  Clayeux,  "C.  R.  Soc.  de  Biol.,"  tome 
V,  1903,  p.  1460.  Baldenweck,  "La  Tribune  Med.,"  Aug.  6,  1904.  Fraser,  "Edin- 
burgh Med.  Jour.,"  Oct.,  1904.  Le  Goic,  "Rev.  de  Med.,"  1904,  p.  631.  Reichel- 
mann,  "Deut.  Zeit.  f.  Chir.,"  1904,  Bd.  74,  p.  354. 

2  Ballantyne,  "Scottish  Med.  and  Surg.  Jour.,"  Nov.,  1S97,  p.  1020.  Arneill. 
"Amer.  Jour,  of  Med.  Sci.,"  Nov.,  1902,  p.  8S5.  Conklin,  " Anatomischer  Anzei- 
ger,"  1903,  Bd.  xxiii,  No.  23.  Pritchard,  "Soc.  for  the  Study  of  Diseases  in  Chil- 
dren," Jan.  15,  1904.  Saigol,  "Indian  Med.  Gazette,"  Nov.,  1903.  Siewert, 
"Berl.  iclin.  Woch.,"  Feb.  8,  1904.  Hartland,  "Lancet,"  April  9,  1904,  p.  1017. 
Fraser,  "Edinburgh  Medico-Chirurg.  Soc,"  July  6,  1904.  Riechelmann,  "Munch. 
med.  Woch.,"  Oct.  25,  1904.  Little,  "Johns  Hopkins  Med.  Soc,"  Nov.  7,  1904, 
report  in  "Med.  News,"  1904.  Kita'j,  "Med.  Soc.  of  Prague,"  Nov.,  1904. 
Habermann,  "Miinch.  med.  Woch.,"  July  26,  1905,  p,   1348. 


VASCULAR   SYSTKM.  485 

taxy,  and  situs  visccrum  inversus.  In  t\i)if  cases  the  organs  are  so 
arranj.,'ed  that  if  o])served  in  a  mirror  they  appear  in  their  normal  positions 
and  relations.  Ballantyne  discusses  many  theories  that  have  been  ad- 
vanced explainintj  the  condition;  none  is  satisfactory.  Transposition 
of  all  the  organs  is  very  much  more  common  than  i)artial  heterotaxy. 
Pic  in  iSq5  collected  iqo  cases  of  more  or  less  complete  transposition. 

Wandering  heart,  mobile  heart,  and  cardioptosis'  are  names  applied 
to  cases  in  whuh  the  heart  shows  unusual  degrees  of  mobility.  In 
such  cases  changes  in  posture  are  attended  by  conspicuous  alterations 
in  the  location  of  the  apex  of  the  organ.  Baric  refers  to  a  case  in  which 
the  movement  amounted  to  14  cm.  Abrams  records  an  instance  in 
which  the  patient  voluntarily  could  displace  the  apex  from  the  fifth 
to  the  seventh  intercostal  space.  In  many  of  these  cases  the  condition 
is  congenital,  and  the  proof  that  it  is  ever  acquired  is  not  conclusive. 
Rummo  thinks  that  it  may  be  acquired,  but  is  due  to  congenital  ab- 
normal predisposition  and  results  from  altered  tone  in  the  great  vessels 
bv  which  it  is  suspended;  deficiency  in  the  elasticity  of  these  structures 
may  also  be  the  cause. 

Any  one  of  these  malpositions  may  be  partial  or  complete,  no  two 
cases  being  equally  marked. 

(b)    acquired    MALPOSITION'. 

The  heart  may  be  displaced  Ijy  pressure  applied  by  neighboring  or 
adjacent  organs:  c.  g.,  by  hydrothorax  pushing  the  organ  toward  the 
unaffected  side;  under  this  head  should  be  included  the  malpositions 
due  to  aneurysm  and  mediastinal  disease. 

Emphysema  of  both  sides  pushes  the  heart  downward;  emphysema 
affecting  one  lung  displaces  the  heart  to  the  opposite  side.  Pleurisy, 
with  contraction,  or  a  contracting  fibroid  pneumonia,  may  pull  the 
heart  toward  the  affected  side.  Vegas  and  Aguilar-  record  an  instance 
in  which  dexiocardia  was  due  to  hydatid  cysts  of  the  left  lung  and 
pleura.  Diaphragmatic  hernia  displaces  the  heart  to  the  right  and 
similar  ectopia  results  from  eventration  of  the  diaphragm.  The  last- 
named  condition  is  a  peculiar  malformation  of  the  diaphragm  charac- 
terized by  absence  of  muscle  on  one  side,  permitting  the  affected  area 
to  ascend  into  the  thoracic  cavity;  the  lung  on  the  side  involved  is 
collapsed  and  the  heart  displaced.  The  stomach,  intestine,  and  spleen 
usually  occupy  the  abnormal  dome-shaped  cavity.  In  hypertrophied 
hearts  the  axes  are  more  nearly  parallel  with  the  axis  of  the  body  and 
nearer  the  median  line. 

M.\LI'()R.\I.\T1()X   ()I-   Till-:    Hi:.\KT' 

I.  Walls,  including  the  septa: 
(a)  Single  cavity. 

•  Barie.  "La  Presse  .Med,"  Jan.  27,  1004,  p.  57:    lyihlioRraphy. 

*  "Rev.  de  la  Soc.  med.  arjjentina,"  September-October,  1904. 

'  For  recent  review  of  cardiac  njalfomiations  see  Thorcl,  "  Lubarsch  and  Oster- 
tag's  Ergcbnisse  d.  allg.  Path.  u.  path.  Anat.,"  Neuntcr  Jahrg.,  I  AVjt.,  1905.  p. 
5S5;  bibliography.  Robinson,  "Bulletin  of  the  Aver  Clinical  Laboratory  of  the 
Penna.  Hosp.,"  Jan.,  1905.  No.  2,  p.  45.  See  also  Sektoen,  "Amer.  Jour,  of  Med. 
Sci.."  Feb..  1901,  vol.  cxxi,  p.  163.  Saillant.  "Soc.  M6d.  des  H6p.,"  1905.  Gar- 
nier,  "La  Presse  Med.."  Dec.  2,  1903,  p.  S30.  Wright  and  Drake,  "Trans,  of 
Assoc,  of  Ainer.  Phys.,"  1903. 


486 


SPECIAL  PATHOLOGY 


(6)  Arrest  of  cardiac  development  with  a  single  auricle  and  a  single 
ventricle,  a  condition  permanent  in  the  chelonia  and  scaly  reptiles. 

(c)  Single  auricle  with  perforate  septum  between  the  ventricles. 

(d)  Single  auricle,  or  a  patent  foramen  ovale,  an  attempt  at  closure 
of  the  septum  between  the  auricles,  with  normal  ventricles. 

2.  Blood-vessels. 

As  in  intrauterine  life  the  vessels  are  developed  from  five  branchial 
arches,  it  is  possible  to  have  innumerable  malformations  of  the  great 
vascular  trunks.     The  following  are  most  frequent : 


Fig     24S  — MALFORilATIOX   OF    THE    HEART.  FiG.    244-— HEART    SHOWING    ABSENCE    OF    .ANTERIOR 

„  ,  ,     ,    ,         ^„       R     p,t„i^„=:  Portion  of  Auricitlar  Septum. 

A.    Fenestrum   in  undefended    space,      is.    Patulous  .  ,  .   ,     ,  in 

ductus  arteriosus.      (Child  one  year  old.)  (Drawing  is  two-thirds  the  natural  size.) 

The  anterior  portion  of  the  septum  is  lacking,  the  re- 
mainder being  largely  membranous  in  structure. 
The  oval  light  area  below  and  slighdy  to  the  right 
of  the  opening  probably  corresponds  to  the  fora- 
men ovale,  although  this  may  be  included  in  the 
opening.  The  patient  had  no  cardiac  symptoms 
and  during  her  fatal  illness  (pneumonia)  there 
was,  at  no  time,  a  suspicion  of  cardiac  abnormality. 
.\ge  thirty-two  years. 

(a)  Patent  septum  between  the  pulmonary  artery  and  aorta,  a 
condition  permanent  in  the  crocodile.  The  fact  that  the  aorta  and 
pulmonary  artery  develop  from  a  single  trunk  renders  the  condition 
possible. 

(b)  Transposition  of  the  vascular  trunks,  the  pulmonary  artery 
arising  from  the  left  heart  and  the  aorta  from  the  right.  In  some 
cases  the  transposition  of  the  vascular  trunks  is  also  associated  with 
transposition  of  the  ventricles,  constituting  what  Rokitansk}'  called 
corrected  transposition. 


VASCULAR  SYSTEM. 


487 


(c)  Double  Aorta. — In  development  there  are  two  primitive  aortas, 
a  right  and  a  left;   ordinarily  the  right  disappears,  but  it  may  not  do  so. 

(d)  Patulous  Ductus  Arteriosus. — When  a  stenosis  of  the  pulmonary 
artery  develops  before  occlusion  of  the  ductus  arteriosus,  the  com- 
munication between  the  aorta  and  pulmonary  artery  may  remain  per- 
manent. There  is  little  difference  between  this  and  a,  except  the 
location,  the  latter  being  immediately  at  the  heart. 

(e)  Stenosis  of  the  pulmonary  artery  is  probably  the  most  frequent 
cardiac  abnormality,  excepting,  of  course,  patulous  foramen  ovale.  The 
degree  of  stenosis  varies,  and  may  be  situated  immediately  at  the 
valvular  orifice  or  slightly  beyond  this  point,  or  may  be  manifest  in 
the  trunk  some  distance  from  the  orifice.  Occasionally,  stenosis  affects 
the  conus  arteriosus.    Stenosis  may  involve  the  aorta. 


Fig.  245.— Heart,  Great  Vessels.  Avn  Lunos  from  a  Case  of  Tra.nsposition  of  the  Vascolak  Trunks. 
Child  lived  thirty-four  days,    .\utopsy  by  Dr.  Ellis.    Philadelphia  Hospital  Specimen. 

.  .\orta  which  arises  from  the  nKht  ventricle.  B.  Right  ventricle  laid  open.  C.  Innominate.  D.  Common 
carotid.  E.  SubclaWan.  F.  Left  branch  of  the  puImon.ary  artery,  the  right  branch  can  be  seen  p.-issinK 
under  the  aorU,  and  from  the  point  wlicre  the  right  and  left  pulmonary  arteries  arc  given  off  by  the  mam  tnink 
(G).  the  ductus  arteriosus  (//)  arises  and  p:issi-s  upwards  to  the  aorta  CI).  /.  Left  aunclc.  /.Right  aunrle. 
K.  Left  pulmonary  vein.  L."  Left  coronarv  artery  which  arises  0.7  cm.  above  the  ongin  of  the  abnomKiUv 
tjaced  aorta.  M.  Left  ventricle.  Notice  that  the  right  ventricular  wall  is  the  thicker  of  the  two. 
lung.    O.  Right  lung. 


N.  Left 


(/)  Atresia  of  the  pulmonary  artery  or  of  the  aorta  is  possible  only 
with  persistent  communication  between  the  two  vessels  beyond  the 
point  of  occlusion. 

3.  Valves. — These  lieing  developed  from  the  endocardium,  may  be 
in  excess  as  to  number  of  leaflets,  or  the  reverse;  a  leaflet  may  be  re- 
dundant or  deficient.  Care  must  be  taken  not  to  confuse  the  results 
of  antenatal  endocardial  disease  with  malformations. 

Hypoplasia  of  the  hejirt  is  occasionally  observed.  The  organ  is 
small. — may  be  less  than  one-half  the  normal  size  and  weight, — and 
usually  possesses  proportionately  small  vessels.  The  vessels  may  be 
hvpoplastic  without  the  heart  showing  marked  abnormality.  The  organ 
mav  be  absent. 

Causes. — Malformation  of  the  heart  is  dependent  upon  arrest  or 
perversion  of  devclojiment.     The  stage  in  its  evolution  at  which  this 


488  SPECIAL  PATHOLOGY. 

occurs  largely  determines  the  character  of  the  malformation.  When 
cardiac  development  is  arrested  early,  the  organ  manifests  the  widest 
deviations  from  the  normal.  When  it  is  delayed  until  later  in  intra- 
uterine life,  or  when  the  usual  circulatory  changes  at  birth  fail  to  take 
their  normal  course,  malformation  is  usually  not  marked,  and  com- 
monly gives  rise  to  no  phenomena  leading  to  a  suspicion  of  its  presence 
later  in  life. 

iVside  from  arrest  of  development,  as  a  cause  of  cardiac  malformation, 
there  can  be  no  doubt  that  antenatal  endocarditis  may  give  rise  to 
changes  in  the  valve  leaflets  or  in  the  orifices  closely  allied  to  those 
seen  as  a  result  of  postnatal  endocardial  inflammation. 

Course  and  Termination. — Aside  from  those  malformations  which 
mechanically  preclude  the  possibility  of  postnatal  circulation,  almost 
no  cardiac  deformity  has  been  described  that  may  be  not  compatible 
with  a  more  or  less  prolonged  extrauterine  existence.  The  accom- 
panying lesions  and  associated  phenomena  are  due  to  circulatory  in- 
efficiency, as  manifested  by  tendency  toward  stagnation  and  the  occur- 
rence of  faulty  aeration.  The  mere  mixing  of  arterial  and  venous 
blood  may  produce  no  symptoms  or  alterations  in  other  organs  or 
tissues.  If  the  blood  can  be  kept  circulating  with  sufficient  activity 
to  secure  aeration  and  to  prevent  venous  distention,  the  patient  may 
escape  any  manifestation  of  the  condition.  The  clubbing  of  the  digits, 
cyanosis  (morbus  coeruleus),  thick  lips,  and  stubby  nose  with  thickened 
alae,  may  all  be  taken  as  evidences  of  disturbed  nutrition.  The 
polycythemia  may  be  truly  remarkable,  as  in  the  case  reported  by 
Baunholtzer:  pulmonary  stenosis  was  present,  and  the  blood  examina- 
tion showed  9,447,000  erythrocytes  and  160  per  cent,  hemoglobin.  The 
relatively  high  specific  gravity  of  the  blood  of  the  new-born  (1060  to 
1070)  often  persists.  Holt  collected  242  cases  of  malformation  of  the 
heart,  in  4  of  which  there  was  an  associated  acute  endocarditis.  Rob- 
inson^ has  been  able  to  collate  17  cases  of  acute  endocarditis  compli- 
cating congenital   malformations;    he  adds   two  original   observations. 

General  atrophy  of  the  heart  occurs  as  the  result  of  general  wasting, 
with  or  without  lessened  work,  the  organ  being  very  much  decreased 
in  size  and  weight.  A  specimen  in  the  writer's  laboratory  weighs  less 
than  three  ounces.  The  condition  can  usually  be  differentiated  from 
hypoplasia  by  the  fact  that  the  blood-vessels  remain  approximately 
normal  in  size,  while  the  corrugations  of  the  pericardium  and  endo- 
cardium indicate  the  diminution  in  volume. 

Local  atrophy  of  the  heart  aflEects  the  left  ventricle,  and  is  probably 
a  sequence  of  disuse.  A  stenotic  mitral  orifice  permits  but  little  blood 
to  flow  into  the  left  ventricle  and  gives  it  but  little  work.  The  nutrition 
is  also  in  most  cases  below  the  normal.  The  condition  is  usually  accom- 
panied by  an  unusual  dilatation  of  the  right  side,  which  may  also  be 
hypertrophied.  Wasting  of  the  left  ventricular  wall,  under  the  fore- 
going circumstances,  is  comparable  to  the  hypoplasia  observed  in  the 
left  ventricle  as  a  result  of  atresia  of  the  aorta,  or  of  the  right  ventricle 
when  the  pulmonary  artery  is  similarly  affected,  in  both  cases  the 
auricular  septum  being  patulous  or  absent. 

Brown  atrophy  of  the  heart  is  due  to  persistent  congestion  of  the 

*  "Bulletin  of  the  Aver  Clinical  Laboratory  of  the  Penna.  Hospital,"  Jan., 
1905,  No.  2,  p.  45. 


VASCULAR   SYSTEM. 


489 


niuscle,  and  is  associated  with  old  age,  inanition,  and  allied  conditions. 
The  ori,'an  is  of  a  dark  chocolate  or  maroon  color,  hard  and  tough, 
diminished  in  size  and  weight,  with  tortuous  vessels  and  wrinkled 
endocardium,  due  to  diminution  in  surface.  Hcmatoidin  or  hemofus- 
cin  is  deposited  in  the  muscle-cell  as  a  granular  pigment,  near  the  ends 
of  the  nucleus  (polar  pigmentation);  the  liber  is  shrunken,  and  there 
is  also,  probably,  a  numeric  decrease.  The  exact  relation  of  this  pig- 
mentation to  wasting  of  the  muscle-fibers  is  not  known.  McCallum' 
states  that  Schiefferdecker  regarded  polar  pigmentation  as  normal  in 
the  heart  of  individuals  after  the  tenth  year.  According  to  Gutch,' 
there  is  a  notable  reduction  in  the  weight  of  the  organ  before  diminution 
in  the  size  of  the  fibers  becomes  demonstrable.  The  muscle-tibers  may 
waste  to  the  point  of  disappearance.  The  fibrous  tissue  may  l)e  notably 
increased,  and  occasionally  distinct  areas  of  induration  may  be  observed. 
(See  Chronic  Myocarditis.) 


£  /)  c 

Fio.  246. — Fatty  I.nfiltration  of  the  Heart  and  Partial  Pekkardial  .\iiiitsii>N. 
.•l..l,.l.   Columns  of  fat   projecting  into  the  myoc.irdium.     B,  B.    Parietal   pcricarfiium  which  is  adherent  to 
the  apex  of  the  lieart  from  C  to  D.     E,  E.    Extrapericardial  fat. 


I  _  Hypertrophy  will  be  considered  after  valvular  disease.  (See  p.  515.) 
M  Fatty  infiltration  of  the  heart  occurs  in  general  ol)esity;  after  the 
permanent  changes  incident  to  pericarditis;  in  chronic  alcoholism; 
occasionally,  in  the  aged  and  the  insane.  There  is  enormous  increase 
in  the  subpericardial  fat;  fat -cells  infiltrate  between  the  muscle-fibers, 
and  probably  incommode  their  action.  Often  the  fat  hangs  as  polypoid 
masses  from  the  apex  of  the  organ  or  along  the  groove  of  the  ven- 
tricular septum.  From  the  margins  of  the  auricles  tuberous  masses 
of  fat,  sometimes  2  cm.  in  thickness,  hang  like  pendulous  new  growths. 
Some  believe  that  atrophy  of  the  fiber  may  be  induced;  during  the 
early  stage  of  the  process  this  is  not  probable,  as  the  fibers  in  the  mass 

'  Anatomischcr  .\nzeiger,  "Centralbl.  f.  die  gesamte  wissenschaftliche  Anat- 
omie."  1897,  Bd.  xiii,  No.  23. 

*   'Jour,  of  Path,  and  Bact    "  Ttmo.  100 1. 


490  SPECIAL  PATHOLOGY. 

are,  usually,  histologically  normal.  The  condition  is  sometimes  spoken 
of  as  lipomatosis  of  the  heart.  It  should  not  be  forgotten  that  this 
condition  constitutes  a  most  frequent  cause  of  sudden  death,  the  over- 
crowded muscle-fibers  failing  to  contract,  or  the  fat,  having  penetrated 
between  the  muscle-fibers,  weakened  the  interlacing  network  and 
led  to  rupture.  The  columns  of  fat  may  extend  through  the  cardiac 
wall,  A  marked  overgrowth  of  the  fat,  and  persistence  of  the  causes 
that  lead  to  its  accumulation,  not  infrequently  terminate  in  an  asso- 
ciated degenerative  change  in  the  muscle-fibers.  Recently  there  has 
been  a  tendency  to  consider  fatty  infiltration  and  fatty  degeneration 
as  identical  processes.  While  freely  admitting  considerable  doubt  as 
to  the  exact  nature  of  the  change  in  each  case,  none  could  consider 
identical  the  changes  represented  by  Fig.  133,  page  226,  and  Fig.  142, 
page  244.  In  some  cases  of  lipomatosis  the  muscle-fiber,  even  where 
the  fat  is  intercalated,  is  normal  in  color  and  texture,  and  often  is 
firm  at  autopsy.  This  condition  is  clearly  distinct  from  the  soft,  flabby 
organ,  the  muscle  of  which  looks  like  washed  meat,  and,  when  sub- 
jected to  the  proper  reagents,  the  fibers  are  found  to  contain  a  substance 
indistinguishable  from  fat;  in  most  of  the  latter  group  of  cases  there 
is  no  increase  in  the  subpericardial  fat  nor  are  columns  of  adipose  tissue 
intercalated  between  the  muscle-fibers. 

Lardaceous  Disease. — ■Albuminoid  or  amyloid  infiltration  of  the  heart 
may  occur  in  the  blood-vessels  of  the  organ  and  in  the  myocardium. 
The  heart  is  undernourished  and  anemic;  milky  opacity  of  the  endo- 
cardium of  the  right  auricle  is  the  most  common  macroscopic  phe- 
nomenon, although  any  of  the  cavities  may  exhibit  the  change.  It 
responds  to  the  usual  stains,  but  can  rarely  be  detected  except  by 
the  microscope.  As  a  rule,  the  alterations  in  the  muscle-fiber  are 
inconspicuous,  the  amyloid  deposit  being  restricted  to  the  blood-vessels 
and  the  connective  tissue  between  the  fibers.  Sometimes  the  deposit  of 
lardacein  is  nodular  rather  than  diffuse.  Such  a  case  was  reported  by 
Steinhaus  ;^  the  amyloid  and  hyaline  nodules  were  irregularly  distributed 
in  the  myocardium. 

Calcareous  infiltration  of  the  heart  may  occur  around  the  auriculo- 
ventricular  orifice,  usually  of  the  left  side,  in  the  valves,  in  the  heart 
muscle,  and  under  the  pericardium.  If  any  of  these  structures  have 
been  inflamed,  infiltration  of  the  inflammatory  products  with  lime  salts 
is  likely  to  ensue.  Deposit  of  lime  salts  is  not  infrequent  in  areas  of 
myocardial  sclerosis  and  in  old  infarcts  and  other  necrotic  areas.  It 
is  also  a  common  occurrence  in  connection  with  tuberculous  and  syphil- 
itic lesions  of  the  myocardium.  In  some  instances  the  extent  of  the 
calcareous  infiltration  was  beyond  anything  that  could  have  been 
anticipated.  In  the  case  reported  by  BramwelP  the  ventricular  wall, 
muscle  columns,  and  even  the  papillary  muscles  were  affected.  Many 
similar^  but  probably  less  marked  cases  have  been  recorded.  In  Du- 
four's  patient  the  deposit  was  nodular.  An  interesting  observation 
in  connection  with  these  cases  is  the  slowness  of  the  pulse,  which  some- 
times ranges  between  30  and  40, 

*  "Zeit.  f.  klin.  Med.,"  vol.  45,  Nos.  5  and  6. 

2  "Edinburs^h  Hospital  Reports,"  vol.  iv,  p.  175. 

3  Pessel,  "Munch,  med.  Woch.,"  June  10,  1902.  Fowler,  "Brit.  Med.  Jovir.," 
April  23,  1904,  p.  952.     Dufour,  "La  Bulle.  Med.,"  Jiine  11,  1904. 


VASCULAR  SYSTKM.  491 

Pigmentary  Infiltration  of  the  Heart. — By  some,  brown  atrophy 
is  considered  as  a  form  of  infiltration  and  is  described  under  this  title. 
(See  p.  4^*^) 

Granular  degeneration  of  the  heart,  or  cloudy  swelling,  is  probably 
an  initial  stage  in  a  form  of  fatty  degeneration.  (Sec  Fig.  139,  p.  242.) 
It  occurs  in  infectious  processes,  such  as  septicemia,  erysipelas,  diph- 
theria, beri-beri,  scarlet  fever,  and  typhoid  fever;  in  hyperpyrexia, 
as  that  of  thermic  fever;  and  in  exhausting  diseases  generally,  such 
as  pernicious  anemia.  The  influence  of  bacterial  toxins  in  the  pro- 
duction of  the  process  can  not  be  doubted.  It  may  be  associated  with 
pericarditis  or  endocarditis,  either  as  a  result  of  the  inflammation  or 
dependent  upon  the  same  cause.  The  heart  muscle  is  softer  than 
normal,  is  slightly  edematous  to  the  touch,  and  is  grayish  and  cloudy, 
in  striking  contrast  to  the  bright  red  of  the  normal.  Rigor  mortis  is 
absent  in  advanced  cases.  The  muscle-cells  are  more  or  less  loaded 
with  granular  debris,  albuminoid  and  not  fatty,  at  this  stage,  as  is 
shown  by  the  granules  clearing  up  when  treated  with  acetic  acid,  and 
not  being  soluble  in  alcohol  or  ether. 

Fatty  degeneration  of  the  heart  occurs:  (i)  As  a  general  process 
invading  the  entire  organ  or  the  whole  of  one  ventricle;  (2)  secondary 
to  some  local  lesion,  and  restricted  to  a  small  area;  (3)  due  to  poisons, 
as  phosphorus. 

I.  Diffuse  or  General  Fatty  Degeneration  of  the  Heart} — This  form 
arises  from  the  same  causes  as,  and  is  probably  merely  a  later  stage 
of,  granular  degeneration.  It  is  frequently  associated  with  arsenic, 
phosphorus,  chloroform,  and  alcohol  poisonings,  and  other  toxic  con- 
ditions. More  or  less  fatty  degeneration  of  the  heart  is  observed  in 
gout,  diabetes,  and  chronic  parenchymatous  nephritis,  particularly  when 
uremia  is  present.  A  varying  quantity  of  fatty  degeneration  will  be 
found  in  the  wasted  hearts  of  chronic  pulmonary  tuberculosis.  The 
papillary  muscles  and  columnae  cameae  of  the  left  ventricle  show  the 
change  to  the  best  advantage;  they  are  light  brown  in  color,  and  run- 
ning across  them  are  yellow  striae,  giving  them  a  brindled,  streaked, 
or  flecked  appearance — "tabby-cat"  or  "tiger-heart";  in  some  instances 
the  muscle  is  pale  yellow  rather  than  brown,  at  other  times  brownish- 
vellow — the  "faded-leaf"  color,  or  "thrush  breast"  appearance;  in 
the  cut  wall  the  fiber  lines  just  below  the  pericardium  are  lost,  and 
the  tissue  appears,  as  a  rule,  uniformly  yellow.  Looking  through  the 
pericardium,  or,  better,  the  endocardium,  the  muscle  shows  yellow  and 
red  striae,  the  latter  being  the  unaffected  fibers.  The  process  is  diffuse 
Itut  not  universal,  comparatively  normal  fibers  lying  next  to  more  or 
less  altered  ones.  The  cardiac  wall  may  be  thinned  as  a  result  of  dila- 
tation, and  the  orifices  may  be  dilated.  The  specific  gravity  of  the 
muscle  is  lessened.  The  myocardium  can  usually  be  readily  pinched 
through.  Microscopic  or  even  macroscopic  hemorrhages  into  the  heart- 
wall  mav  be  present.  Under  the  microscope  the  affected  fibers  are 
loaded  with  minute  oil  globules  not  larger  than  a  red  corpuscle.     They 

'  Satterthwaite,  "Med.  News,"  Feb.  2,  1901.  Robinson,  "  Phila.  Med.  Jour.." 
Mav  II,  1901,  also  "Amer.  Jour,  of  Med.  Sci.,"  June.  1901.  Pratt,  "Johns  Hop- 
kin's  Hosp.  Bull.,"  Oct.,  1004.  Bolton.  "Lancet,"  Feb.  4,  1905.  P-  278.  Cowan, 
'  lour,  of  Path,  and  Bact.,"  June,  IQ02.  vol.  viii,  p.  177.  Thorel,  "Lubarsch  and 
Ostertag's  Ergebnisse  d.  allgem.  Path.  u.  path.  Anat.."  Neunter  Jahr.  I.  Abt. 
1Q03.  p.  612. 


492 


SPECIAL  PATHOLOGY. 


gt^. 


^y  «^*  ••.-- 


^ 


differ  from  granular  fibers  in  that  the  fat  is  darkened  by  osmic  acid, 
and  may  be  dissolved  in  ether.  (See  Demonstration  of  Fat,  p.  244.) 
Dunharn'  believes  that  the  notable  swelling  present  in  the  fibers,  during 
the  earlier  stages  of  the  process,  may  be  due  to  the  fact  that  the  fiber 
takes  up  nutritional  substances  that  it  can  not  properly  convert;  this 
belief  is  in  line  with  the  conviction  of  other  observers  that  the  process 
partakes  of  some  of  the  characters  of  an  infiltration.  According  to 
Cowan,  the  cement  substance  between  the  cells  and  the  nuclei  never 
becomes  fatty.  In  some  cases  fat  droplets  can  be  demonstrated  in 
the  capillary  endothelium,  and  in  such  instances  the  myocardial  change 
is  usually  most  marked  immediately  around  the  affected  vessels  (para- 
arterial  or  peri-arterial  form). 

The  termination  of  the  granular  and  fatty  metamorphoses  is  likely 
to  be  the  same:    (a)  sudden  syncope  and  death  from  failure  to  contract; 

(b)  gradual  failure  by  reason  of 
•    ,.„,.:.._;_-;r.5-^ .  increasing    incompetency    to 

maintain  the  circulation.  Rup- 
ture of  the  heart  is  not  common 
in  diffuse  or  general  fatt}^  de- 
generation of  the  organ,  as  the 
cardiac  muscle  has  not  the  power 
so  to  raise  the  intracardiac 
pressure  as  to  endanger  the 
weakened  walls.  It  is  probable 
that,  in  the  granular  stage,  re- 
generation and  recovery  may 
ensue;  this  becomes  less  likely 
as  the  fatty  stage  advances. 
Clinicians  commonly  maintain 
that  repair  is  possible  even  when 
fatty  change  is  advanced.  Under 
such  circumstances  it  is  held 
that  the  destroyed  fiber  is  ab- 
sorbed and  the  adjacent  fibers 
undergo  hypertrophy,  and  in 
that  way  compensate  for  the 
tissue  that  has  been  lost.  As  it 
is  not  improbable  that  in  cardiac 
hypertrophy  new  fibers  are  formed,  with  the  associated  enlargement  of 
existing  fibers,  the  possibility  of  a  similar  change  following  the  subsidence 
of  the  disorder  at  present  under  consideration  must  be  admitted. 

2.  The  second  form  of  fatty  degeneration  is  sometimes  spoken  of  as 
partial  or  local.  It  is  due  to  a  local  ischemia,  such  as  results  from  ath- 
eroma, calcification,  embolic  plugging,  or  thrombosis  of  some  branch  of 
the  coronary  arteries,  which  are,  to  a  certain  extent,  terminal.  The 
lesion  is  manifested  by  the  presence  of  a  softened  spot  in  the  ventricular 
wall,  pale  yellowish-brown  in  color,  frequently  greasy  to  the  touch,  and 
occasionally  containing  oil  globules,  visible  macroscopically.  Some- 
times the  degenerated  area  is  surrounded  by  a  zone  of  hyperemia.  The 
rapidity  with  which  the  process  develops  varies  in  different  cases,  de- 
pending upon  the  promptness  with  which  the  cause  acts.  When  there 
^"Med.  Record,"  Feb.  16,  1901. 


;..»o:' 


Fig.  247. — Fatty  Degexeratiox  of  the  Heart. 
(Specimen  fi-xed  in  osmic  acid,  rendering  the  fat 
globules  black.) 

Near  the  center  of  the  drawing  are  a  number  of  red  blood- 
cells.  {From  a  case  oj  pernicious  anemia  in  the  Jej- 
jerson  Medical  College  Hospital,  seri'ice  oj  Professor 
J .  C.  Wilson.) 


VASCULAR   SYSTIiM.  495 

has  been  a  sudden  occlusion  of  tlie  l)lood-sui»i)ly.  the  process  will  com- 
monly be  rapid.  On  the  other  hand,  when  the  local  change  is  brought 
about  by  gradual  encroachment  ui)on  the  lumen  of  the  coronary  artery 
or  a -branch,  the  lesion  is  delayed,  and  opportunities  are  afforded  for  an 
associated  overgrowth  of  fibrous  tissue.  As  a  rule,  the  degenerative 
change  is  limited  to  a  single  focus,  which  is  located  on  the  anterior  aspect 
of  the  left  ventricle  near  the  apex.  Less  commonly,  a  corresponding 
point  on  the  wall  of  the  right  ventricle  is  involved.  The  degenerated 
area  is  rarely  large,  as  the  conditions  that  bring  it  about,  if  affecting  a 
considerable  extent  of  the  cardiac  w^all,  usually  cause  death  before  the 
manifestation  of  any  degenerative  lesion.  Occasionally,  more  than  one 
area  is  involved.  Microscopically,  the  changes  already  described  are 
more  marked  than  in  the  general  variety,  as  the  patient  usually  lives 
longer,  and  the  small  focus  advances  further.  The  process  may  be  fol- 
lowed by:  (a)  Rupture,  which  is  rare  in  the  general  degeneration;  (6) 
aneurvsmal  bulging;  (t)  fibroid  processes  may  convert  the  mass  into 
cicatricial  tissue;  (d)  the  area  may  be  so  small  as  to  give  no  determining 
phenomena.     (See  Infarction  of  the  Coronary  Arteries.) 

3.  The  third  form  of  fatty  degeneration, — that  due  to  poisoning. — 
toxic  Jegeticratioii  of  the  heart  lunscle,  results  most  commonly  from  phos- 
phorus," but  occasionally  from  arsenic  and  antimony.  It  presents  the 
changes  already  given,  and  responds  to  the  general  stain  and  chemic 
tests  of  the  ordinary  fatty  degeneration ;  if  an  opinion  is  to  be  given  in 
a  suspected  poisoning  case  as  to  the  presence  or  absence  of  fatty  degenera- 
tion, it  must  be  formed,  if  it  is  possible  to  form  such  an  opinion,  while 
the  tissue  is  fresh.  The  term  toxic  degeneration  is  not  altogether  appro- 
priate, as  the  degenerative  changes  resulting  from  various  infections  are 
essentially  of  toxic  origin. 

Hyaline  degeneration  of  the  heart  differs  from  the  albuminoid  or  gran- 
ular ehan,i,^e  in  that  the  heart  muscle-tibers  are  converted  into  a  hyaline, 
vitreous  substance  resembling  the  material  that  results  from  the  vitreous 
change  in  other  muscles,  known  as  Zenker's  degeneration.  When  present, 
the  structural  alteration  has  been  discovered  by  the  microscope  and  not 
by  macroscopic  evidences.  In  hyaline  degeneration  the  muscle-tibers 
may  be  fragmented;  the  separation  of  the  fragments  may  be  at  the  junc- 
tion of  the  muscle-cells  or  directly  through  the  cell -wall.  When  this 
condition  is  present,  Renaut  has  proposed  the  name  segmentary  myocar- 
ditis, or  myocardial  segmentation  or  fragmentation,'  Bulig  is  of  the 
opinion  that  many,  if  not  all.  mstanccs  of  segmentation  and  fragmen- 
tation are  artifacts  produced  by  the  microtome  knife.  Strekeisen 
believes  that  the  fragmentation  is  dependent  u])on  violent  cardiac  con- 
tractions during  the  agonal  period.  He  holds  that  a  preliminary 
weakening  of  the  muscles  is  not  necessary  to  the  occurrence  of  frag- 
mentation, as  shown  by  the  frequency  with  which  it  occurs  when 
death  has  been  due  to  accident  and  when  no  associated  lesions  can 
be  detected. 

Postmortem  Changes  in  the  Myocardium. — Peculiar  patches  of  a  yel- 
lowish or  grayish-yellow  color,  situated  immediately  under  the  pericar- 

'  Thorel.  "Lubarsch  and  Ostertajj's  Ergebnisse  d.  allgem.  Path.  vi.  path. 
Anat.."  Xeunter  Jahr.  I.  Abt.  1Q03.  p.  622.  Buhlig.  "Jour.  Med.  Research." 
May,  1002.  MacCalKim.  ' Anatomischer  Anzeiger."  1897.  xiij,  p.  6oq.  Giaco- 
melli.  "  Rif.  Med."  Nov.   7,,  4,  and  5,  igo2. 


494  SPECIAL  PATHOLOGY. 

dium,  have  been  noticed.  They  usually  contain  bacteria,  but  not  the  tis- 
sue reactions  incident  to  an  infection.  The  change  resembles,  in  a 
limited  way,  an  embolic  process.  Weber  regards  the  condition  as  a 
postmortem  change  in  an  area  of  infection,  which  infection  occurred  just 
before  death. 

Myocarditis,  or  inflammation  of  the  cardiac  muscle,  may  be  acute 
or  chronic,  local  or  diffuse,  and,  though  primary  types  have  been 
described,  it  is  probably  always  secondary  to  some  other  affection. 
With  regard  to  the  genesis  of  the  condition,  one  of  the  first  difficulties 
encountered  is  differentiation  of  inflammation  from  some  of  the  degener- 
ative changes  described  in  previ  us  pages.  The  scope  of  this  work  does 
not  permit  a  discussion  of  the  clinical  and  pathologic  phases  of  the 
subject.  It  may  be  stated,  however,  that  clinicians  and  pathologists 
are  not  agreed  as  to  the  line  that  may  be  drawn  between  myocardial  de- 
generations, necrosis,  and  inflammations.  There  are  points  at  which  the 
three  conditions  appear  to  become  indistinguishable.  For  the  purpose 
of  this  work  acute  myocarditis  may  be  divided  into  the  simple  and 
suppurative,  and  the  chronic  myocarditis  into  the  fibroid,  and  fibro- 
elastic  or  elastic  types. 

The  term  acute  parenchymatous  myocarditis  has  been  applied  to  the 
lesior  s  that  I  have  characterized  above  as  degenerative.  Theoretically 
in  this  form  the  alteration  is  restricted  to  the  muscle-fiber  with  no  im- 
portant alteration  and  no  cellular  infiltration  in  the  interstitial  tissue. 
The  condition  possesses  no  anatomic  feature  or  clinical  character  by 
which  it  may  be  separated  from  some  of  the  myocardial  degenerations. 
For  these  reasons  my  inclination  is  to  suppress  the  term. 

Acute  nonsuppurative  or  simple  myocarditis  ^  is  observed  in  acute  in- 
fectious diseases,  particularly  those  due  to  organisms  incapable  of  pro- 
ducing suppuration.  The  condition  is  observed  in  rheumatism,  diph- 
theria, influenza,  chronic  uremia,  smallpox,  and  occasionally  in  pneu- 
monia, typhoid,  malaria,  and  syphilis.  The  essential  feature  in  its  pro- 
duction seems  to  be  intense  toxemia,  and  apparently  the  condition  may 
occur  without  the  presence  of  bacteria  in  the  myocardium.  In  cases 
reported  by  Sellentin  bacteria  were  not  found  in  the  aft'ected  myocardium 
nor  was  there  evidence  of  infection  in  other  tissues.  According  to 
Escudero,  the  myocarditis  of  influenza  may  be  of  the  acute,  nonsuppura- 
tive type,  in  which  case  it  is  toxic,  or  mixed  infection  may  give  rise 
to  the  suppurative  lesion.  It  has  been  observed  in  tuberculosis  even 
when  there  was  no  evidenc  of  the  tubercle  bacillus  in  the  myocardial 
structures. 

^  The  following  references  on  acute  myocarditis  may  be  consulted:  Thorel, 
"L^-'  ^rsch  and  Ostertag's  Ergebnisse  d.  allgem.  Path.  u.  path.  Anat.,"  Neunter 
Jah.  .  Abt.  190:!,  632.  Hektoen,  "Jour. of  Path,  and  Bact.,"  Jan. ,1896.  Freund, 
"Ben.  klin.  Woch.,"  Dec.  5  and  12,  189S.  Gibson,  "The  Practitioner,"  Jan., 
1901.  Bianchini,  "  Riv.  di  patol.  nerv.  e  ment.,"  1901,  No.  9.  Aubertin  and 
Babonneix,  "Gaz.  des  Hop.,"  Aug.  8,  1901.  Merklen,  "La  Presse  M6d.,"  Dec.  4, 
1901.  Stengel,  "Jour.  Amer.  Med.  Assoc."  Dec.  14,  1901.  Fisher,  "Brit.  Med. 
Jour.,"  Sept.  27,  1902,  p.  949.  Cowan,  "Jour,  of  Path,  and  Bact.,"  Aug.,  1903, 
p.  87.  Guido,  "Brit.  Jour,  of  Child.  Dis.,"  vol.  i,  No.  12.  Sotti,  "Arch,  per  le 
So.  med.,"  1904,  vol.  xxviii;  also  "  Giornale  della  R.  Accad.  di  Med.  di  Torino," 
February-March,  1904.  Carpenter,  "Lancet,"  Oct.  i,  1904,  p.  94?-  Schmaltz, 
"Miinch.  med.  Woch.,"  Aug.  9,  1904.  White  and  Smith,  "Boston  Med.  and  Svirg. 
Jour.,"  Oct.  20,  1904.  Sellentin,  "Zeit.  f.  klin.  Med.,"  1904,  Bd.  liv,  p.  298.  Es- 
cudero, "Argentina  Med.,"  Nov.  19,  1904. 


VASCULAR  SYSTKM.  495 

Morbid  Anatomy. — The  heart  is  usually  softer  than  normal  and,  as 
a  rule,  pale.  In  some  cases,  however,  the  color  is  dark  and  beefy,  but 
rarelv  uniformlv  so.  When  local  or  nodular,  pale  grayish  areas  indif- 
ferentlv  outlined  may  sometimes  be  recognized.  Histologically  the 
muscle-tibers  are  swollen,  the  nuclei  obscured,  and  the  interstitial  tis- 
sue of  the  affected  area  contains  mononuclear  cells,  some  of  which  may 
possess  the  morphology  and  stain  reaction  of  plasma  cells.  In  advanced 
cases  areas  can  be  found  in  which  the  muscle-fibers  have  disappeared, 
the  space  so  created  being  occupied  by  mononuclear  cells.  The  per- 
centage of  these  cases  in  which  recovery  occurs  is  not  known,  nor  are  we 
in  possession  of  any  accurate  inform^^-on  as  to  the  later  changes  in 
patients  who  survive.  It  has  been  held  that  the  acute,  nonsuppurative, 
interstitial  mvocarditis  may  constitute  the  basis  of  a  chronic  fibroid 
lesion  that  develops  later.  There  can  be  no  doubt  that  the  cardiac 
svmptoms,  in  many  acute  infectious  diseases,  may  be  due,  at  least  in 
part,  to  acute,  nonsuppurative  myocardial  inflammation. 

Acute  suppurative  myocarditis — myocardial  abscess  or  metastatic 
abscess  of  the  heart — usually  follows  an  infection  of  the  cardiac  wall 
induced  bv  the  deposit  of  infected  emboli.  The  condition  is  most 
frequent  in  pyemia  and  septicemia,  and  particularly  in  such  mycoses 
of  the  blood  as  commonly  accompany  osteomyelitis,  suppurative  throm- 
bophlebitis, and  endocarditis  due  to  pyogenic  organisms.  In  other  cases 
the  infection  results  from  extension  of  bacteria  from  the  endocardium  or 
myocardium.  The  foci  of  suppuration  are  usually  situated  in  the  an- 
terior portion  of  the  left  ventricular  wall.  In  the  earlier  stages  they 
present  the  gross  appearances  of  an  infarct;  later,  pus  may  be  evident, 
and  may  burrow  toward  the  endocardium  or  the  pericardium.  The 
abscesses  are  rarely  large,  are  not  infrequently  microscopic,  but  may 
attain  a  diameter  of  0.25  to  0.5  cm.  The  adjacent  heart  muscle  usually 
shows  the  changes  incident  to  infective  processes  independent  of  actual 
bacterial  invasion. 

Chronic  interstitial  or  sclerotic  myocarditis^  (also  called  productive 
myocarditis,  fibrous  transformation,  fibrous  degeneration  of  the  myo- 
cardium, and  fibrous  infiltration)  is  a  chronic  process  associated  with 
the  formation  of  fibrous  tissue  in  the  myocardium. 

Causes. — Although  not  established  beyond  the  possibility  of  a  doubt, 
it  is  probable  that  acute  nonsuppurative  interstitial  myocarditis  may 
lead  to  the  chronic  fibroid  form.  The  most  frequent  cause  of  myocar- 
dial induration  is  disease  of  the  coronary  ar^'^ry  of  such  a  type  as  to  lessen 
the  blood-supplv  in  the  main  trunk  or  in  one  or  more  of  its  branches. 
This  influence  may  result  from  atheroma  of  the  aorta  so  situated 
as  to  involve  the  coronan,'-  artery  at  its  point  of  egress ;  a  nodula--  ring 
often  surrounds   the   coronarv  in   such   a  wav  as  clearlv  to  less*    ^th'> 

»  Thorel,  "  Lubarsch  and  Ostertag's  Ergebnisse  d.  allgem.  Path.  u.  path.  Anat.," 
Xeunter  Jahr.  I.  Abt.  1903,  p.  645.  Fujinami,  "Virchow's  Arch.,"  1900,  Bd.  159, 
p.  447.  Musser,  "Medical  News,"  Jan.  11,  1902.  also  April  19,  1902.  Cowan, 
'Jour,  of  Path,  and  Bact.,"  Dec,  1903,  p.  210.  Gibson.  "Lancet,"  Dec.  j.  1903- 
p.  1565.  Jackson,  "Boston  Med.  and  Siirg.  Jour.."  Sept.  29.  1904.  Aschoff. 
"Arch,  de  Med.  Exper.  et  d'Anat.  Path.."  ISiov.,  1904.  p.  984.  Marchiafava. 
"Revista  Crit.  di  Clin.  Med.,"  April  23.  1904.  Zuppinger,  "Arch.  f.  Kindcrheil- 
kunde,"  vol.  xxxv.  Camac,  "Johns  Hopkins  Hosp.  Bull.."  Feb..  1904.  vol.  xv. 
Coplin.  "Proceed,  of  Path.  Soc.  of  Phila.,"  n.  s..  vol.  vi.  Mouriquaud,  "See.  des 
Sci.  M6d.  de  Lyon,"  Feb.  i,  1905- 


496 


SPECIAL  PATHOLOGY. 


lumen  and  reduce  the  quantity  of  blood  that  enters  the  vessel.  In  other 
cases  the  sclerotic  process  affects  one  or  more  of  the  coronary  branches, 
producing  a  local  effect  on  nutrition  and  terminating  in  the  evolution 
of  a  more  or  less  circumscribed  area  of  so-called  fibroid  myocarditis. 
The  branch  usually  affected  is  the  anterior  interventricular  stem,  usually 
in  the  lower  third' of  the  course.  In  the  heart  from  which  the  diagram 
shown  in  Fig.  248  was  made  the  periventricular  branch  was  affected, 
and  at  this  point  a  notable  increase  in  fibrous  tissue  and  a  proportionate 
wasting  of  the  muscle  occurred,  giving  rise  to  slight  aneurysmal  bulging. 


Fig. 


24S. — Diagram   Showing    the    Distribution   of  the    Coronary  Artery   in    a    Case    of    Local 

Fibroid  Myocarditis. 

Aorta.  B.  Pulmonarv  artery.  C.  Superior  vena  cava.  D.  Posterior  interventricular  branch  of  the  right 
coronary  artery.  E.  Auriciilar  appendage.  F.  Right  auricular  branch.  G.  Right  coronary  artery.  H. 
Periventricular  branch.  /.  Right  marginal  branch.  /.  Posterior  interventricular  branch  of  the  right  coro- 
nary arterv.  K.  Left  coronary  arterj'.  L.  Terminal  branch  of  the  left  coronary  artery.  J/.  Anterior 
interventricular  branch  of  the  left  coronary  artery.  -V.  Occluded  artery  corresponding  in  position  to  the  left 
periventricular  branch.  The  left  marginal  branch  was  farther  to  the  side  and  could  not  be  indicated  in  this 
drawing  without  causing  confusion.  O.  Point  of  occlusion.  P,  P.  The  dotted  line  marks  the  border  of  the 
most  advanced  myosclerotic  area. 


So  constantly  is  fibroid  myocarditis  associated  with  disease  of  the  nu- 
trient vessels  that  Musser  has  suggested  calHng  the  condition  coronary 
arterv  disease.  It  may  also  accompany  chronic  endocarditis,  either 
associated  with,  or  independent  of,  valvular  incompetency  or  stenosis. 
Chronic  inflammations  of  the  pericardium,  congestion  of  the  cardiac 
veins,  increased  venous  tension,  such  as  is  seen  in  emphysema ,  in^-erstitial 
pneumonia,  and  chronic  pleurisy,  are  also  causes.  It  is  a  more  or  less 
constant  lesion  in  failing  compensation,  and  constitutes  one  of  the  mani- 
festations of  syphilis  and  of  malaria.     It  is  maintained  that  the  sclerotic 


VASCULAR  SYSTKM. 


40/ 


Fig.  249.— Arteriosclerotic  Disease  of  the  Coronary  Artery  Giving  Rise  to  Progressive  Obliteration 

OF  its  Lumen. 
Section  taken  from  sdcrolic  pcrivi-nlricular  branch  shown  in  Y'\%.  248.     The  clastic  lamella;  are  fragmentcfi,  the 

endothelium  has  iirolifirated,  and  a  forming;  tlirombus  is  rapidly  otcludinR  the  vessel. 
A.  Forming  thrombus  covered  at  most  points  by  endothelium.  B.  Channel  through  thrombus  with  partial  wasting 
of  adjacent  vessel  wall.  C,  C.  Transverse  .section  of  muscle-libt-rs.  showing  fragmentation  and  retraction 
from  the  myocardial  skeleton.  /).  Unusu;dly  conspicuous,  app.ircnily  swollen  clastica;  the  same  change  can 
be  seen  in  many  parts  of  the  field.  The  tine  stipple  effect  in  the  lower  part  of  the  figure,  and  especially 
marked  in  the  lower  right,  is  due  to  transverse  sectioning  of  elastic  fibers. 


Nv.. 


X 


Fic.  J50. — Chronic  MYocARDins. — (Schmaus.  .-. 

Cardiac   musclc-lil)crs.     6.6.  Newly  formed  tibrous  connective  tissue.     This  can  often  be  demon.stratcti  to  be  of 
different  ages,  and  in  the  older  parts  calcareous  change  may  have  iiccurred. 


33 


498  SPECIAL   PATHOLOGY. 

changes  of  myocarditis  may  be  consecutive  to  myocardial  degeneration 
and  necrobiosis  brought  about  by  various  bacterial  toxins.  The  librous 
increase  has  been  experimentally  produced  by  pyocyaneus-toxin  (Char- 
rin),  and  the  poison  of  the  diphtheria  bacillus  is  believed  to  lead  to 
lesions  of  the  muscle-fibers  followed  by  fibroid  increase  (Mollard  and 
Regaud).  It  is  generally  conceded  that  the  fibrosis  is  secondary  to 
alterations  in  the  muscle-fiber  and  not  the  reverse.  The  statement 
that  it  may  result  from  rupture  of  the  muscle-fibers  is  not  accompanied 
by  satisfactory  proof. 

Morbid  Anatomy. — The  preceding  review  of  the  important  causes  of 
fibroid  myocarditis  suggests  the  recognition  of  two  forms.  In  one  of 
these  the  process  is  more  or  less  sharply  outlined,  and  constitutes  what 
may  be  called  the  local  or  circumscribed  form  of  the  affection.  In  other 
cases  the  process  is  dififuse,  a  large  part  of  the  myocardium  is  affected, 
although  the  change  is  not  uniform.  To  this  condition  has  been  given 
the  name  diffuse  interstitial  myocarditis.  Weber  and  also  Huchard  have 
proposed  certain  subdivisions  based  upon  the  histology  of  the  affected 
tissues.  It  is  possible  to  recognize  a  perivascular  type  in  which  the 
fibrous  tissue  immediately  surrounds  the  blood-vessels  distributed  in  the 
myocardium.  In  other  cases  the  sclerosis  appears  to  bear  no  relation 
to  branches  of  the  coronary  artery,  and  for  this  the  name  dystrophic 
/i6ro5i5  has  been  proposed.  Letulle  was  the  first  to  call  attention  to  the 
fact  that  in  some  of  these  cases  the  new  tissue  is  largely  elastica,  and  for 
this  condition  he  proposed  the  name  elastic  myosclerosis.  Like  the  simple 
fibroid  types,  this  form  may  be  diffuse  or  circumscribed.  In  some  cases 
of  myosclerosis  the  involved  areas  are  extremely  hard,  and  for  such  the 
name  myosclerosis  dure  has  been  suggested ;  when  the  affected  areas  are 
soft,  the  condition  is  called  myosclerosis  ntolle. 

Local  or  circumscribed  fibrous  myocarditis  is  usually  attributed  to 
a  cause  that  has  affected  only  a  part  of  the  cardiac  wall,  such  as  the 
anemia  following  gradual  occlusion  of  a  branch  of  the  coronary  artery, 
infarction,  and  local  fatty  degeneration.  The  fibrous  area  may  be 
small,  irregularly  outlined,  and  less  than  one  centimeter  in  diameter. 
It  may  or  may  not  extend  through  the  heart-wall.  In  other  cases 
the  area  of  fibrosis  may  equal  one-third  of  the  ventricular  wall,  and  in 
some  instances  larger  areas  have  been  found.  The  process  is  most  fre- 
quent at  or  near  the  apex  of  the  left  ventricle.  When  full}'  developed, 
the  fibrous  area  is  dense,  like  a  cicatrix,  constituting  the  so-called  "heart- 
scar."  Some  of  the  collections  of  fibrous  tissue  probably  represent 
efforts  at  repair  in  areas  of  past  necrosis.  The  fibrous  tissue  may  contain 
-pigment  and  calcareous  matter,  and  muscle-fibers  may  be  absent.  The 
presence  of  pigment  is  suggestive  of  hemorrhagic  infarction.  When 
the  entire  thickness  of  the  heart -wall  is  involved,  and  even  sometimes 
when  only  a  part  has  become  fibroid,  aneurysmal  bulging  may  occur. 
The  more  or  less  sharply  outlined  margin,  at  times  observed,  has  led  to 
the  belief  that  some  of  these  heart-scars  are  really  gummata.  The  occur- 
rence of  scars  of  evidently  different  ages,  associated  with  the  presence  of 
absorbing  gummata,  would  certainly  seem  to  be  conclusive. 

In  the  diffuse  interstitial  myocarditis  the  fibrous  tissue  is  widely, 
but  not  uniformly,  distributed.  The  abundance  of  the  new  tissue  be- 
tween the  cardiac  muscle-fibers  has  to  a  certain  extent  justified  the  ap- 
pellation fibroid  infiltration.     Most  observers,  as  already  stated,  do  not 


VASCULAR   SYSTEM. 


490 


consider  the  increase  of  fibrous  tissue  an  evidence  of  past  or  existing 
inflammation,  but  rather  a  substitutive  fibrosis,  the  fibrous  tissue  having 
replaced  atrophied,  degenerated,  or  necrotic  muscle-fibers. 

M/.^rbid  Aiuitonty. — The  cardiac  muscle  is  usually  firmer  than  normal ; 
this  abnormal  density  is  not  uniform  in  distribution.  Occasionally, 
whitish  areas  of  sclerosis  may  l)e  recognized  in  the  ventricular  wall. 
White  lines  are  frequently  present  on  the  columna?  carneae;  the  tendons 
of  the  papillary  muscles  seem  to  be  projected  toward  the  cardiac  wall 
as  whitish  streaks,  often  extending  nearly  to  the  base  of  the  papillae. 
Under  the  microscope,  fibrous  tissue  can  often  be  demonstrated  in 
various  stages  of  development.  Not  infrequently  calcareous  infiltration 
is  present,  and  the  muscle-tibers  usually  show  some  granular  change, 


.4.  Endocardium  greatly  thickcnc<l  and  rich  in  elastica.     B.  .\ncry  «-ith  enormous  increase  in  elastica  and  pro- 
liferation in  intima.     Other  vessels  show  similar  changes.     C.  Vessel  practically  occluded  by  a  thriml.ii. 


and  occasionally  pigmentation.  Interference  with  function  is  always 
probable:  it  mav  1>e  .slight,  but  in  most  instances  dilatation  comes 
on  rapidly  and  gradual  failure  of  the  heart  takes  place. 

Local  or  circumscribed  elastic  myocarditis  does  not  differ  conspicu- 
ouslv  from  the  fibroid  form;  the  distribution  is  essentially  the  same  in 
both.  The  affected  tissue  is  softer,  lighter  in  color,  and  usually  more 
vascular  than  in  the  purely  fibroid  type.  When  approaching  the  peri- 
cardium or  endocardium,  especially  the  latter,  and  when  involving  the 
columna?  carneae,  or  papillary  muscles,  a  bright,  grayish,  shiny  appear- 
ance, resembling  mother-of-pearl,  is  produced.  Histologically  the  most 
striking  feature  is  the  encirmous  increase  in  the. elastica.     This  substance 


500 


SPECIAL  PATHOLOGY. 


can  be  seen  as  rather  coarse  wavy  fibrils,  the  direction  of  which  cor- 
responds to  the  course  originally  taken  by  the  muscle-fibers. 

Diffuse  elastic  myocarditis,  in  the  milder  cases,  gives  rise  to  no  gross 
alteration.  The  muscle  may  be  normal  in  color  and  elasticity ;  usually 
when  pinched  there  is  more  resistance  than  in  health.  In  some  cases  a 
slight  grayish  opacity  is  present  beneath  the  endocardium,  but  often  this 
is  not  marked ;  histologically  the  distribution  of  the  hyperplastic  elastica 
is  more  likely  to  be  nodular  and  perivascular  than  the  fibrous  tissue  of  the 
dystrophic  type.  The  origin  of  the  newly  formed  elastic  ^tissue  is  usually 
obscure ;   in  some  of  the  perivascular  lesions  it  may  be  possible  that  it 


Fig.  252. — Heart,  Elastic  Myocarditis. 
Transverse  section  of  a  muscle  column  at  the  point  where  it  joins  the  ventricular  myocardium. 
A.  \Vhat  appears  to  be  the  remains  of  a  central  vessel.  Around  this  are  arranged  the  concentric  laminae  of  svifollen 
and  at  points  fragmented  elastica.  The  tine  granules  between  the  strands  are  transverse  sections  of  elastica 
disposed  longitudinally.  B,  B.  Thickened  endocardium.  At  this  point  the  section  shows  the  elastica  to  be 
cut,  for  the  most  part,  transversely.  C,  C.  Points  of  hemorrhage  immediately  beneath  the  endocardium. 
The  lower  part  of  the  field  is  occupied  by  altered  myocardium.  Many  of  the  muscle-fibers  are  granular,  some 
appear  vacuolated,  and  the  interstitial  fibrous  tissue  is  increased. 

arises  from  the  elastica  of  the  blood-vessels.  The  relatively  broad  bands, 
that  can  sometimes  be  seen  immediately  beneath  the  endocardium, 
could  not  result  from  proliferation  of  the  elastica  of  the  normal  vessels, 
and,  as  Letulle  suggests,  must  have  arisen  from  the  elastic  skeleton 
of  the  myocardium.  It  is  reasonable  to  assume  that  in  elastic  myo- 
carditis the  propulsive  action  of  the  heart  is  less  disturbed  than  in  the 
fibroid  myosclerosis.  The  clinical  histories  of  some  of  the  cases  support 
this  suggestion.  In  some  cases  both  fibroid  and  elastic  myocarditis 
are  concurrent. 


VASCULAR   SYSTEM, 


50; 


Aneurysm  of  the  heart  results  from  any  of  the  preceding  conditions 
which,  at  any  one  point,  lessen  the  resistance  of  the  cardiac  wall.  Bulj^ing 
occurs,  the  wall  of  the  aneurysm  beini^  either  a  saccular  mass  without 
constriction  or  a  large  sac  communicating  with  the  ventricle  by  a  small 
opening.  A  specimen  in  the  writer's  lal)oratory  ])ossesses  a  sac  as  large 
as  an  egg,  its  wall  being  made  up  of  the  endocardium,  a  layer  of  fibrous 
tissue,  and  the  pericardium;  the  cavity  of  the  aneurysm  communicates 
with  the  ventricle  by  a  small  opening  near  the  apex  about  one  centi- 
meter in  diameter.  In  over  sixty  per  cent,  of  the  reported  cases  the 
aneurysm  is  in  the  left  ventricular  wall,  usually  near  the  apex.  Rarely, 
the  aneurysmal  dilatation  begins  in  the  septum.  When  the  aneurysm 
is  composed  of  a  dilated  pouch  communicating  with  the  ventricular 
cavity  through  a  small  opening,  thrombi  are  not  infrequentlv  present. 
As  a  result  of  roughening  in  the  wall  of  the  aneurysm  a  thrombus  may 
form,  even  when  there  is  no  opportunity  afforded  for  stagnation  of  the 
blood.  Sometimes  the  aneurysmal  wall  is  intensely  calcific.  The  author 
has  observed  a  case  in  which  the  whole  of  the  aneurysm  was  attached 
to  the  parietal  pericardium,  suggesting  the  possibility  of  pericardial 
adhesions  dragging  the  fibroid  wall  outward,  and  in  that  way  favoring 
the  local  dilatation,  the  cause  of  w^hich  must  be  principally  the  intra- 
ventricular pressure.  Rupture  occurs  in  nearly  all  cases,  and  death 
almost  instantaneously  follows. 

Diseases  of  the  blood-vessels  supplying  the  heart  do  not  commonly 
diflfer  from  similar  alterations  observed  in  the  arteries  elsewhere.  The 
fact  that  the  coronary  arteries  are  more  or  less  terminal,  in  the  sense 
that  abundant  anastomosis  is  not  afiforded.  leads  to  changes  in  the 
cardiac  wall  differing  somewhat  from  tissue  alterations  secondarv  to 
vascular  lesions  in  other  organs. 

Atheroma  of  tlw  coronary  arteries,  obliterative  arteritis,  and  fatty 
degeneration  of  the  intima  and  media  occur  under  the  same  conditions 
and  from  the  same  causes  as  observed  elsewhere.  Atheroma  and  ob- 
literative change  are  frequently  associated  with  syphilis,  and  mav  con- 
stitute a  part  of  the  fibroid  change  occurring  in  the  organ  in  this  disease. 
Both  atheroma  and  obliterative  arteritis  lessen  the  carrving  capacity 
of  the  vessel,  lower  the  nutrition  of  the  cardiac  muscle  in  the  area  bevond, 
and  favor  the  occurrence  of  fibroid  change.  Huchard  analvzed  145 
cases  of  angina  pectoris  in  which  the  postmortem  showed  that  in  128 
of  the  cases  the  coronary  artery  was  diseased. 

Fortunately,  the  coronary  arteries  are  rarely  the  sites  of  thrombosis 
and  embolism.  Atheroma  and  obliterative  change  favor  the  occurrence 
of  thrombosis.  Embolism  is  less  frequent.  With  the  occlusion  of  the 
artery,  the  nutrition  of  the  area  beyond  is  suspended,  and  later  that 
portion  of  the  myocardium  involved  undergoes  necrosis  terminating  in 
rapid  softening,  the  resulting  condition  constituting  a  form  of  what  the 
older  writers  called  myomalacia  cordis.  With  the  presence  of  infected 
emboli  in  the  blood,  and  possibly  as  a  result  of  mural  implantation  of 
bacteria  circulating  in  the  coronary  vessels,  metastatic  abscesses  are 
engendered  in  the  myocardium.  (See  Embolism,  p.  278;  also  Acute 
Suppurative  Myocarditis,  p.  495.) 

Aneurysm  of  the  coronary  artery  is  rare.  It  may  result  from 
atheroma  or  degenerative  <  hanges  \n  the  arterial  wall,  and  is  said  to 
occur  as  a  result  of  inflammation  or  degeneration  involving  the  adjacent 


502  SPECIAL  PATHOLOGY. 

muscle.  According  to  Griffith/  there  are  twenty -four  cases  of  coronary 
aneurysm  on  record;  in  seven  of  the  reported  instances  the  aneurysm 
was  multiple;  in  one  case  there  were  twelve.  Death  from  rupture  and 
consequent  hemorrhage  occurred  in  about  half  the  cases. 

Syphilis-  of  the  myocardium  may  attack  the  blood-vessels,  inter- 
stitial tissue,  or  muscle.  The  vascular  lesion  may  be  a  gummatous 
arteritis  or  the  ordinary  type  of  arteriosclerosis.  The  changes  in  the 
vessels  by  altering  the  blood-supply  may  produce  a  secondary  fibroid 
myocarditis.  The  last  lesion  sometimes  occurs  independently  of  marked 
coronary  disease  and  may  be  diffuse  or  distributed  in  small  nodes  (mili- 
ary gummata)  throughout  the  organ.  A  diffuse  syphilitic  degenerative 
change  of  the  muscle-fibers  of  the  heart  has  been  described.  A  most 
striking  manifestation  of  syphilis  is  the  cardiac  gumma.  The  older  of 
these  are  gray,  yellowish-gray,  or  hyaline,  contain  areas  of  necrosis 
which  are  sometimes  caseous,  and  may  attain  a  diameter  of  3  cm.  to 
4  cm.  The  lesion  is  usually  situated  in  the  left  ventricular  wall,  some- 
times along  the  septum  and  rarely  on  the  right  side.  Usually  cardiac 
gumma  is  solitary.  Amyloid  infiltration  and  hyaline  degeneration  of 
the  vessels  and  muscle-fibers  may  accompany  syphilis.  In  hereditary 
syphilis  diffuse  fibroid  induration  is  sometimes  present  and  gummata 
have  been  described.  Mracek  and  also  Hektoen  have  reported  instances 
of  multiple  foci  of  interstitial  myocarditis  due  to  hereditary  syphilis. 

Tuberculosis^  of  the  heart  may  involve  any  part  of  the  organ.  Fer- 
rand  and  Rathery,  Oettinger  and  Braillon,  and  others  have  recorded 
instances  of  tuberculous  endocarditis;  Tessier  was  able  to  collect  forty- 
seven  cases  in  which  endocardial  lesions  accompanied  tuberculosis. 
Anders  reported  the  seventy-second  case  of  tuberculosis  of  the  myocar- 
dium. It  is  doubtful  if  the  heart  is  ever  primarily  affected,  the  involve- 
ment usually  being  secondary  to  pulmonary,  peribronchial,  or  medias- 
tinal tuberculosis.  Anatomically  the  lesion  may  be  of  the  miliary  type, 
which  necessarily  represents  a  hematogenous  infection.  Many  years 
ago  Weigert  expressed  the  belief  that  the  heart  was  frequently  involved 
in  miliary  tuberculosis.  Tuberculous  pericarditis,  especially  the  case- 
ous form,  may  infiltrate  the  myocardium.  (See  Fig.  241,  p.  478.) 
The  most  frequent  manifestation  of  cardiac  tuberculosis  is  the  large 
solitary  caseous  or  calcareocaseous  mass  which  may  attain  a  diameter 
of  4  cm.  to  5  cm.  Any  part  of  the  heart  may  be  affected,  but  in  nearly 
half  of  the  cases  the  lesion  is  in  the  left  ventricle.  The  caseous  mass  is 
usually  situated  externally;  the  cardiac  wall  may  be  penetrated,  and 
the  cheesy  material  discharged  into  the  blood-stream,  giving  rise  to 
miliary   tuberculosis.     A  diffuse  fibroid  myocarditis  is  sometimes  seen 

1  "Brit.  Med.  Jovir.,"  Feb.  2,  190 1. 

'Weber,  "Med.  Record,"  Aug.  29,  1903,  p.  321.  Adler,  "Med.  Record,"  Feb. 
20,  1904,  p.  281.  Cecikas.  "Rev.  de  med.,"  Dec,  1904.  Stockmann,  "  Ueber 
Gummiknoten  in  herzfleische  bei  Erwachsenen,"  Bergmann,  Wiesbaden,  1904. 
Romanov,  "  Roussk.  Vratch,"  Nov.  6,  1904. 

'  Moser,  "Med.  and  Surg.  Reports  of  the  Boston  City  Hospital,"  eleventh 
series,  1900.  Crawford,  "Edinburgh  Med.  Joiir.,"  Sept.,  1901.  Heineman,  "Lan- 
cet," Dec.  28,  1901.  Anders,  "Jour.  Amer.  Med.  Assoc,"  Nov.  i,  1902,  p.  1081. 
Sotti,  "Arch,  per  le  Sc  med.,"  1904,  vol.  xxviii.  Raviart  and  Caudron,  "Echo 
Med.  du  Nord,"  Nov.  6,  1904.  Silbergleit,  "Virchow's  Arch.,"  Feb.  i,  1905,  Bd. 
179,  p.  283.  Schwarz,  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.,"  April  15,  1905. 
Ferrand  and  Rathery,  "La  Med.  Mod.,"  Feb.  18,  1903.  Oettinger  and  Braillon, 
"Soc  Med.  des  Hop.  de  Paris,"  July  15,  1904. 


VASCULAR  SYSTEM.  503 

in  tuberculosis  and  has  been  attributed  to  the  poison  of  the  tubercle 
bacillus.  Sotti  has  reported  two  cases  of  hemorrhagic  tuberculous  myo- 
carditis;   the  lesion  may  be  focal  or  disseminated  throughout  the  organ. 

Actinomycosis'  of  the  heart  is  rare,  is  usually  due  to  extension  from 
a  primary  lesion  in  contiguous  tissues,  and  may  be  attended  by 
numerous  tistuhc  o]'cnnig  externally. 

Tumors-  of  the  heart  are  of  infrequent  occurrence.  About  forty 
instances  of  primary  cardiac  neoplasm  have  been  reported.  Of  the  150 
collected  by  Cornib  in  1Q02,  secondary  growths  were  ten  times  as  fre- 
quent as  the  primary.  Sarcoma  is  the  most  rf)mmon  of  the  primary 
neoplasms,  although  rhabdomyoma,  myxoma,  fibroma,  and  chondroma 
have  Iteen  observed.  Secondary  tumors  of  the  organ  may  result  from 
extension  from  some  contiguous  viscus  or  mediastinal  tissues.  Most 
instances  of  secondary  tumors  of  the  heart  due  to  extension  have  been 
from  primary  cancers  of  the  esophagus.  By  the  blood-stream,  the  car- 
diac tumor  may  be  due  to  implantation  among  the  muscle  columns,  or 
invasion  bv  the  coronary  vessels.  Propagated  neoplastic  thromlii  may 
reach  the  heart  by  the  larger  veins.  Statistics  show  that  the  tumor 
most  likelv  to  give  rise  to  metastasis  in  the  heart  is  sarcoma  of  bone. 
Most  of  the  pedunculated  tumors  of  the  heart  attached  to  the  septum 
and  projecting  into  the  left  ventricle  are  more  or  less  perfectly  organized 
thrombi. 

Hydatid  cysts ^  of  the  heart  have  been  reported.  In  the  cases  recorded 
by  Altmann  and  by  Quill  death  resulted  from  cysts  blocking  the  pul- 
monary artery. 

Rupture^  of  the  heart  may  be  traumatic  or  pathologic:  I  think  we 
mav  exclude  the  so-called  idiopathic,  on  the  ground  that  the  normal  heart 
does  not  rupture.  Ruptures  resulting  from  blows  on  the  chest,  crushes, 
and  falls  are  more  frequent  on  the  right  side,  and  in  the  auricles,  owing 
to  the  fact  that  the  walls  of  these  cavities  are  thinner  than  the  left  ven- 
tricle, and  also  because  the  right  ventricle  is  so  situated  that  it  receives 
the  brunt  of  any  external  injury  transmitted  through  the  anterior  chest 
wall.  The  pathologic  ruptures  are  due  to  diseases  of  the  myocardium 
and  usuallv  (seventy-five  to  eighty  per  cent,  of  the  cases)  involve  the 
left  ventricle.  Three-fourths  of  the  pathologic  ru])tures  are  due  to  some 
form  of  fatty  disease  of  the  heart.  Infarction,  aneurysm,  abscess  of  the 
myocardium,  cysts,  and  tumors  account  for  the  remaining  cases.  The 
rupture  mav  be  sinfilc  or  multiple,  complete  or  partial.  As  many  as  six 
or  seven  distinct  ruptures  may  be  present.  With  a  rupture  extending 
through  the  wall  or  from  the  pericardium  nearly  to  the  endocardium,  or 
in  the  reverse  direction,  there  may  be  purely  intramural  tears  in  the 
muscle,  as  shown  by  hemorrhages  into  the  myocardium  at  the  point  of 

»  Schrotter.  XX  German  Conp.  Intern.  Med.  Wiesbaden,  April.  1902. 

»Geibel."  Central bl.  f.  allg.  Path.  u.  path.  Anat.,"  1899.  x.  848.  Curtis,  "L'Echo 
Med.  du  Nord."  July  10.  1904.  Sainmont,  These  de  Paris.  1903.  Cagnetlo. 
"Arch,  per  le  Sc.  Med.."  1904-  t-.     •       "u 

'Altmann.  "Intercolonial  Jour,  of  Australasia,"  Dec.  20,  1902.  Davies.  Hy- 
datid Disease,"  1894.  Masovic.  "Wien.  med.  Woch..  "  1904.  No.  9.  Quill.  "Jour, 
of  Royal  Army  Med.  Corps."  April.  1904. 

'  Ercklentz.  "Zeit.  f.  klin.  Med.  Berlin,"  xliy.  Nos.  5  and  6.  Grout.  "Amer. 
Med,"  April  12.  1902.  Revenstorf.  "Mittheil.  a.  d.  Grtnzgeb.  d.  Med.  u.  Chir." 
Bd.  xi,  H.  4.  p.  60^.  Hamilton,  "Phila.  Med.  Jour."  Jan.  24.  1903-  foott  and 
Hall,  "Lancet."  Jan.  16.  1904.  p.  152.  Winkler.  "La  Presse  M6d.."  Feb.  22,  1905. 
p.  117. 


504 


SPECIAL  PATHOLOGY. 


rupture.  Ruptures  are  not  of  necessity  fatal;  and  even  when  multiple, 
death  may  be  delayed  for  days  or  weeks.  A  rupture  of  any  size,  per- 
mitting rapid  evacuation  of  the  ventricle,  leads  to  sudden  death.  In 
the  smaller  ruptures,  that  leak  but  little,  recovery  is  possible.  The 
great  obstacle  to  recovery  from  rupture  of  the  heart  is  the  fact  that  the 
conditions  that  bring  about  the  rupture  lessen  the  reparative  power  of 
the  organ. 

Wounds^  of,  and  foreign  bodies- in,  the  myocardium  are  tolerated  by 
the  organ  about  as  well  as  similar  lesions  are  borne  by  other  structures. 
Stewart  has  been  able  toicollate  sixty  cases  of  cardiac  wound  operated 
upon,  with  recovery  of  38.5  per  cent.  The  dangers  are  hemorrhage  and 
infection,  and,  if  these  can  be  avoided,  cicatrization  is  accomplished 
with  little  difficulty.  Regeneration  of  the  myocardium  can  not  be  ex- 
pected. Foreign  bodies  are  occasionally  present  in  the  heart  without 
giving  rise  to  any  symptoms.  Bullets  healed  in  the  heart  wall  have 
been  reported  by  Riethus,  Brown,  and  others.  Brown's  patient  carried 
an  old-time  musket  ball  in  the  myocardium  of  the  left  ventricle  for 
thirty-six  years.  The  bullet  may  be  free  in  the  ventricular  cavity;  but 
usually,  when  so  situated,  it  becomes  entangled  in  the  spaces  between 
the  muscle  columns  and  is  attached  by  an  organized  clot. 


ENDOCARDIUM. 

The  normal  endocardium  is  composed  of  a  flattened  layer  of  connec- 
tive-tissue cells — histologically,  a  serous  membrane.  The  continuous 
flow  of  blood  over  its  surface,  and  the  difference  in  function  from  other 
serous  membranes,  render  a  separate  description  of  its  diseases  necessary. 
The  membrane  is  nonvascular  even  in  its  reflected  layers,  which,  rein- 
forced by  fibrous  and  elastic  tissues,  form  the  valves.  The  latter  struc- 
tures are  rich  in  lymphatics,  through  which  the  nourishment  of  the 
supporting  framework  is  maintained.  Recent  investigations  seem  to 
show  that  the  bases  of  the  mitral  and  tricuspid  leaflets  contain  some 
capillary  ramifications;  the  blood-vessels  do  not,  however,  approach 
the  free  edges  of  the  valves.  Immediately  beneath  the  endocardium 
ramifies  the  plexus  of  nerves  described  by  Krause. 

INFLAMMATION    OF    THE    ENDOCARDIUM ENDOCARDITIS.^ 

General  Considerations  ;  Classification. — That  part  of  the  endocar- 
dium sustaining  the  most  stress,  other  things  being  equal,  will  first  suf- 
fer and  suffer  most.  Recognition  of  this  fact  explains  the  infrequency 
of  the  process  on  the  right  side  in  adult  life,  and  the  rarity  of  intra- 
uterine disease  of  the  left  side;  it  elucidates  those  cases  of  secondary 
endocardial  inflammation  of  the  right  side,  in  adult  life,  when  extensive 
obstructive  or  regurgitant  lesion  of  the  left  side  raises  the  tension  and 
increases  work  of  the  right  heart.     When  the  inflammation  is  in  the  val- 

*  Stewart,  "Amer.  Jour,  of  Med.  Sci.,"  Sept.,  1904. 

=*  Editorial,  "  Phila.  Med.  Jour.,"  April  27,  1901.  Brown,  "Trans.  West  Vir- 
ginia Med.  Assoc,"  1902,  p.  720.  Riethus,  "Deut.  Zeit.  f.  Chir.,"  vol.  Ixvii.  Fis- 
cher, "Deut.  med.  Woch.,"  Aug.  28,  1902.  Koch,  "Berl.  klin.  Woch.,"  1904, 
July  II,  No.  28. 

3  Thorel,  "  Lubarsch  and  Ostertag's  Ergebnisse  d.  allgem.  Path.  u.  path.  Anat.," 
1903,   Neunter  Jahr.    I.   Abt.,   p.   683. 


VASCULAR  SYSTEM.  505 

vular  endocardium,  it  is  known  as  valvular  endocarditis,  or  valvulitis; 
when  on  the  auricular  or  ventricular  wall,  it  is  spoken  ot  as  mural  endo- 
carditis ;  the  latter  is  rare  except  in  the  malignant  and  atluroniatous 
forms.  In  the  adult  about  one-half  of  the  cases  of  endocarditis  attack 
the  mitral  leaflets;  of  the  remaining  fifty  per  cent.,  a])Out  ninety- 
four  per  cent,  involve  the  aortic  cusps;  the  remaining  cases  arc  divided 
between  the  valves  of  the  right  side,  the  tricuspid  being  the  more  com- 
monly affected. 

Inflammation  of  the  endocardium  may  be  aciilc  or  cliro)iic.  It  has 
been  customary  for  pathologists  and  clinicians  to  divide  the  acute  in- 
flammations of  the  endocardium  into  simple  and  nialig}ia)it.  It  was  be- 
lieved that  the  acute  sim])le  endocarditis  was  noninfective  in  origin,  and 
that  it  was  not  associated  with  the  presence  of  bacteria.  The  tendency 
at  present  is  to  regard  both  forms  as  dependent  upon  infection,  but  in 
that  type  previously  called  simple  endocarditis,  the  infection  differs  in 
degree,  or  possibly  in  character,  from  that  seen  in  the  ulcerative  variety. 
Both  pathologically  and  clinically,  cases  are  not  infrequently  seen  in 
which  the  clinical  history  and  morbid  anatomy  justify  the  term  simple 
endocarditis.  It  is  equally  true  that  we  occasionally  find  extensive 
lesions,  affecting  the  valves  and  mural  endocardium,  associated  w^th 
pyogenic  infection,  and  also,  although  less  commonly,  with  other  my- 
coses, clinically  and  anatomically  meriting  the  name  ulcerative  or  ma- 
lignant endocarditis.  Between  these  extremes  there  is  a  middle  ground, 
occupied  by  a  not  very  small  number  of  cases,  in  which  it  is  quite  impos- 
sible, either  anatomically  or  clinically,  to  separate  and  group  them  with 
one  or  the  other  of  the  foregoing  divisions.  The  possible  identification 
of  differences  once  believed  to  be  clearly  recognizable  is  further  compli- 
cated by  the  more  recent  introduction  of  the  term  acute  malignant 
rheumatic  endocarditis,'  and  applying  it  to  a  form  of  endocardial  in- 
flammation of  rheumatic  origin,  usually  terminating  fatally,  without 
the  tendency  to  suppurative  lesions  in  other  viscera,  and  unassociated 
with  the  rather  characteristic  temperature-curve  of  that  form  of  endo- 
cardial inflammation  that  we  have  been  in  the  habit  of  calling  malignant 
endocarditis.  It  is  to  be  presumed  that  the  easily  recognized  differences 
between  the  typical,  clearly  defined,  acute,  simple  endocarditis  and  the 
admittedly  malignant  endocarditis  must  depend  upon  the  character  of 
the  infection  and  upon  the  resistance  of  the  tissues  to  the  infective 
agent.  Thus,  infection  manifested  by  the  presence  of  staphylococci 
will  usually  be  ulcerative  in  type,  while  the  endocardial  inflammations 
accompanying  rheumatism  rarely  assume  the  general  characters  of  the 
ulcerative  form  of  endocarditis.  Bearing  the  foregoing  facts  in  mind, 
and  rememl)ering  that  the  so-called  acute  simi:)le  endocarditis  may  or 
may  not  terminate  in  the  malignant,  I  shall  adhere  to  the  customary 
division,  based  upon  the  belief  that  it  is  possible  to  recognize  an  acute 
simple  endocarditis  and  an  acute  malignant  endocarditis. 

The  chronic,  indurative,  sclerotic,  or  interstitial  endocarditis  is  still  to 
be  regarded  as  an  entity,  although  it  often  is  nothing  more  than  a  termi- 
nal stage  of  an  acute  process. 

'  Litten,  "  Berl.  klin.  VVoch.  "  18Q9.  The  same  observer,  more  recently  ("Deut. 
med.  Woch.."  May  22  and  29,  1902),  has  proposed  to  divide  acute  endocarditis 
into  (i)  benign.  (2)  septic  ulcerative,  (.5)  nonseptic  ulcerative.  In  the  latter  form 
evidence  of  ulceration  is  present,  but  patients  do  not  manifest  the  usual  phe- 
nomena of  sepsis. 


5o6  SPECIAL  PATHOLOGY 

Acute  Simple  Endocarditis. — Causes. — The  most  frequent  cause  of 
this  form  of  endocarditis  is  acute  articular  rheumatism.^  Litten's  sta- 
tistics show  that  in  30,000  patients  there  were  400  cases  of  endocarditis, 
thirty-five  per  cent,  of  which  were  due  to  rheumatism.  Although  there 
may  be  some  doubt  as  to  the  specificity  of  the  organism  found  in  rheu- 
matism, the  infectious  nature  of  the  disease  is  generally  accepted. 
Frequently  endocarditis  is  preceded  by  tonsillitis,  and,  as  this  may  be 
rheumatic,  such  cases  belong  with  those  due  to  the  first -mentioned  group 
of  causes.  The  fact  that  in  some  cases  of  endocarditis  following  ton- 
sillitis other  bacteria  have  been  observed  indicates  that  the  tonsil-  may 
be  the  portal  through  which  infection  occurs  in  types  of  the  affection 
other  than  pure  rheumatic  endocarditis.  The  endocarditis  accompany- 
ing or  following  pneumonia^  and  due  to  the  pneumococcus  is  sometimes 
of  the  form  at  present  under  consideration;  often,  however,  it  resembles 
the  ulcerative  or  malignant  type.  Kerchensteiner  believes  that  pneu- 
mococcus endocarditis  is,  anatomically,  midway  between  the  verrucose 
and  ulcerative  forms.  Endocarditis  of  this  type  may  follow  other  acute 
infectious  diseases,^  among  which  should  be  mentioned  diphtheria," 
scarlet  fever,"  mumps, ^  influenza,*  and  erysipelas.  The  association  of 
endocarditis  and  chorea^  is  probably  due  to  the  fact  that  in  certain  in- 
stances both  are  infectious  diseases;  streptococci  have  been  isolated 
from  the  blood  in  a  number  of  these  cases.  Debilitating  diseases  that 
depress  the  antimicrobic  functions  are  frequently  accompanied  by  endo- 
carditis; among  such  affections  should  be  mentioned  gout,  diabetes, 
and  renal  disease  and  degeneration,  especially  chronic  interstitial  neph- 
ritis. The  relation  of  trauma^"  to  acute  and  chronic  lesions  of  the 
endocardium  has  been  variously  estimated;  there  are,  however,  un- 
doubted instances  in  which  valve  rupture  and  subsequent  inflammation 
have  followed  violent  exertion  and  chest  injuries.  Pleasants  has  been 
able  to  collect  fourteen  cases  of  endocarditis  believed  to  have  been  of 
traumatic  origin;  to  these  the  three  reported  by  Sinnhuber  should  be 
added.  In  a  few  cases  endocarditis  had  resulted  from  transplacental 
infection."  Previous  attacks  increase  susceptibility  to  the  disease. 
Robinson^'  has  been  able  to  collect  seventeen  cases  of  acute  endo- 
carditis associated  with  congenital  malformation  of  the  heart. 

^  For  references  see  second  foot-note,  p.  112  ;  also  consult  Lewis  and  Longcope, 
"Amer.  Jour,  of  Med.  Sci.,"  Oct.,  1904,  p.  601.  Harrass,  "Munch,  med.  Woch.," 
Aug.  30,  1904.     Cole,  "Jour,  of  Infect.  Disease,"  Nov.  5,  1904,  p.  714. 

-  Gurich,  "Munch,  med.  Woch.,"  Nov.  22,  1904. 

2  Preble,  "Amer.  Jour,  of  Med.  Sci.,"  Nov.,  1904,  p.  783:    full  bibliography. 

*  Weaver,    "Ft.   Wayne   Med.   Magazine,"   Nov.,    1904. 
^  Jtunp,  "Pediatrics,"  Aug.,  1903. 

"Spencer,   "Lancet,"   Feb.  19,  1905,  p.  420, 

'  Tatschner,  "Wien.  med.  Woch.,"  July  30,  1904. 

*  Flexner,  "Univ.  of  Penna.  Med.  Bull.,"  Jan.,  1903,  p.  551;  also  Escudero. 
"Argentina  Med.,"  Nov,  19,  1904. 

^"Hirshberg,  "Jour,  of  the  Alumni  Assoc,  of  the  College  of  Physicians  and 
Surgeons,  Baltimore,"  April,  1903. 

'"Pleasants,  "Bull,  of  Johns  Hopkins  Hosp.,"  1903,  vol.  xiv,  p.  124.  Lib- 
man,  "N.  Y.  Path.  Soc,"  Oct.  8.  1902.  Strumpler,  "Miinch.  med.  Woch.," 
Julv  14,  1903.      Sinnhuber,  "  Deut.  med.  Woch.,"  1904,  xxx,  No.  32,  p.   1161. 

'"  Ballantyne,  "Manual  of  Antenatal  Pathology  and  Hygiene."  Fisher,  "  Re- 
ports of  the  Societv  for  the  Study  of  Diseases  in  Children,"  1902,  vol.  ii. 

12  "Bull,  of  the  Ayer  Clinical  Laboratory  of  the  Pennsylvania  Hospital,"  Jan., 
1905,  No.  2,  p.  45. 


VASCULAR  SYSTEM. 


507 


At  the  present  time  few  doubt  the  infectious  nature  of  acute  endo- 
carditis. A  number  of  bacteria,  mostly  micrococci,  have  been  found  in 
the  valves  and  superimposed  vegetation.  A])parently  the  same  organ- 
isms occur  in  the  so-called  acute  sim])le  endocarditis  and  the  malignant 
forms  of  the  afTection.  The  clinical  and  anatomic  differences  between 
the  two  classes  probably  depend  upon  the  pathogenic  cajiacity  of  the 
organism  or  the  varying  susceptibility  of  the  infected  patients.  All 
forms  of  acute  endocarditis  are  constantly  associated  with  morbid  proc- 
esses admittedly  of  microorganismal  origin,  and  an  extended  study  of 
the  aflfection.  by  recent  methods,  has  led  to  the  frequent  isolation  of 
bacteria  from  the  blood  during  life  and  from  the  cardiac  lesions  post- 


Fic.    253.  —  .\oRTic    Orifice    Laid    Ope.v,    Showing    the    Valve    Leaflets,    Acute    Endocarditis  — 

{Redrawn  from  Schnuius.) 

A .  Line  of  contact  with  beginning  formation  of  vcKeLiiions.     B.  More  advanced  and  larger  vegetations  closely 
simulating  in  appearance  an  ulcerative  lesion.     Between  the  Icatlcl  A  and  the  Icatlct  imnu-ii,ii<  K  .vI.om-  tlic 
letter  B  is  seen  a  single  vegetation  on  the  leaflet  B;  should  a  similar  lesion  occur  at  the 
on  the  leaflet  .4,  the  two,  coming  together,  could  coalesce,  or  the  continued  deposit  of 
adjacent  masses,  and,  by  organization,  would  produce  an  .i.lh.-iic.n  L.twcn  the  two  Ic.ii' 
ing  the  orifice. 

mortem.     The  attempts  to  establish  a  specitic  organism  for  endocar- 
ditis have  been  unsuccessful. 

Heiberg  and  Winge  in  1869  demonstrated  bacteria  in  the  lesions  of 
endocarditis.  Harblitz'  analyzed  the  records  upon  the  subject,  and 
believed  that  it  might  be  possible  to  differentiate  some  of  the  infections 
bv  the  character  of  the  lesion;  streptococcus  infections  produce  large 
vegetations  that  progress  slowly  and  are  accompanied  by  nephritis. 
In  the  pyemic  endocardial  lesions  containing  the  ordinary  staphylococci 
the  course  of  the  disease  is  usually  more  rapid,  the  valve  destruction 

'  Harblitz,  "Om  Endokardit,  dens  Pathologiske  Anatomi.  og  Aetiologi," 
1897.     Harblitz.  "Deutsch.  med.  Woe'-    "   ?■'••'■     -'     i'^'" 


5o8  SPECIAL  PATHOLOGY. 

greater  and  associated  with  more  wide -spread  infection.  Extended 
observations  have  shown  that  the  morbid  anatomy  is  insufficient  to  dif- 
ferentiate the  lesions  produced  by  one  germ  from  those  due  to  other  bac- 
teria, and  that  the  same  microbe  may  be  found  in  both  ulcerative  and 
verrucose  types  of  the  affection. 

In  addition  to  the  Diplococcus  rheumaticus/  the  organisms  usually 
found  in  endocarditis  belong  to  the  pyococcic  group,  and  include  the 
staphylococci,  streptococci,  pneumococcus,  and  gonococcus.^  According 
to  Preble,  there  are  one  hundred  and  thirty-two  reported  cases  of  pneu- 
mococcus endocarditis.  About  thirty  accurately  observed  instances  of 
gonococcal  endocarditis^  are  on  record.  Among  the  organisms  less  fre- 
quently found  are  the  colon  bacillus,  bacillus  of  Friedlander,  Bacillus 
typhosus.  Bacillus  diphtheriae,  Micrococcus  endocarditidis  rugatus 
(Weichselbaum),  Micrococcus  endocarditidis  capsulatus  (Weichselbaum), 
Micrococcus  zymogenes.  Bacillus  endocarditidis  griseus  (Weichselbaum), 
Bacillus  endocarditidis  capsulatus,  and  the  tubercle  bacillus.  Warfield 
and  Walker^  report  a  case  of  acute  ulcerative 
endocarditis  due  to  the  meningococcus. 

Morbid  Anatomy!" — The  alterations  observed 
in  this  condition  may  be  more  or  less  arbitrarily 
divided  into  two  stages,  the  first  of  which  terminates 
with  the  formation  of  vegetations.  Redness  and 
injection  are  not  present,  as  the  tissue  is  nonvascu- 
lar, (a)  The  milky  opacity  of  the  membrane  is  due 
^'^'Dms^oF^HE^MfxA^"  ^^  serum  and  leukocytes  infiltrating  the  lymph- 
v.^vE.  Section  AT  LixE  spaccs  of  the  affectcd  leaflet,  and  to  slight  roughen- 
gramm'aticO^-WJ-  ing  of  the  endothelial  surface;  the  latter  change 
ters^'*'*  ^  1°  d  1  a m e -  produccs  an  cff cct  similar  to  that  which  results  from 
fl,  a'.  Endocardium,  which  at  grinding  the  surfacc  of  glass.  {h)  Bogginess  or 
aSd'and  covereYbv  edema  of  the  valve  is  discernible  at  this  time,  and 
the  cap  of  fibrin,  d.   b.     is  due  to  the  infiltration  of  the  valve  tissue  bv  serum 

Interstitial  tissue  of  the  jii  ^  t.i-  r,  i  11' 

valve  with  newly  formed      and  Icukocytcs.     in  this  sottcned  and  boggy  con- 
ma?^n?f vfive lea^e't.'' ^      dition,  the  valves  pounding  against  one  another  at 
the  rate  of   from   120  to   150  times  a  minute,  (c) 
abrasion  or  even  laceration  may  occur.     The  line  of 
friction  is  the  line  of  contact,  and  in  this  line  the  roughened  points  de- 
velop.    A  microscopic  examination  of  the  valve  in  this  stage  will  show 
more  or  less  necrosis  of  the  endothelium,  associated  with  desquamation, 
and  in  some  cases  hyaline  degeneration  or  distinct  coagulation  necrosis. 
The  subendocardial  connective-tissue  cells  and  fibrils  are  not  infrequently 
swollen,  and  the  lymph-spaces  of  the  valve  may  contain  fibrin.     The 
elastica  of  the  affected  leaflet  is  swollen  and  may  be  fragmented. 

The  Production  of  Vegetations. — The  blood  passing  over  the  rough- 
ened line  of  abrasion  deposits  a  cap  of  fibrin  upon  the  rough  points ;  to 
this  are  added  cells  produced  by  proliferation  of  the  connective-tissue 

'  See  p.   112. 

^  See  p.    107. 

^  Harris  and  Johnston,  "Bull,  of  Johns  Hopkins  Hospital,"  1902,  vol.  xiii,  p. 
236. 

*  "Btill.  of  the  Aver  Clinical  Laboratory  of  the  Pennsylvania  Hospital,  "  Oct., 
1903,  No.  I,  p.  81. 

^  For  the  histology  of  endocarditis  see  Koniger,  Arbeit,  a.  d.  Path.  Inst.  Leip- 
sic,    1903. 


VASCULAR  SYSTEM. 


5oy 


elements  and  a  further  infiltration  of  leukocytes  into  the  afTected  valve. 
These  chanties  are  most  marked  beneath  the  area  of  rouj^heninp,  and 
increase  the  size  of  the  so-called  vegetation  or  cap  of  fihrin.  The  de- 
posited fibrin  may  be  granular,  fibrillar,  or,  less  frequently,  hyaline. 
The  distinctly  hyaline  form  of  fibrin  is  rarely  present;  when  found,  it 
occurs  as  small  irregular  collections  in  the  forming  vegetation.  It 
should  be  observed  that  structurally  and  genetically  the  developed  vege- 
tation is  essentially  a  thrombus.  It  may  contain  all  the  bodies  commonly 
found     in    thrombi, — 

fibrin,    leukocytes,    ery-  ^  ^ 

thocytes,  and  platelets, 
— and  is  subject  to  sec- 
ondary changes  identical 
with  those  occurring  in 
thrombi.  (See  Throm- 
bosis, p.  270.)' 

With  firm  vegeta- 
tions of  moderate  size 
the  lesion  is  called  endo- 
carditis verrucosa  ;  when 
the  collection  of  fibrin 
is  large  and  flabby,  the 
term  polypous  or  villous 
endocarditis  is  at  times 
apjilifd. 

Changes  iu  the  Fibrin 
Cap  or  Vegetation. — The 
vegetation  sometimes 
increases  by  layers  and 
may,  in  this  way,  be- 
come distinctly  strati- 
fied; it  may  be  redis- 
solved.  As  a  result  of 
its  large  size  vasculariz- 
ation, and  consequent 
organization,  are  often 
impossible;  the  bacteria 
present,  or  their  toxins,  yi,..i...i,..i.  p.ipiiiarymus( 
m a v   cause    softening  ?"''  .'";'•■■''•''  'hitkcninK.   j 

-  .  1-1  fibroKl  ihiclccninK.     1  he  whole  fri- 

(further  necrosis)  which 
terminates  in  fragmen- 
tation, the  resulting  |)ar- 
ticles  constituting  em- 
boli. If  near  a  corresi)onding  inass,  on  an  apposed  leaflet,  especially  at  the 
valvular  attachment,  cohesion  of  two  vegetations  may  constitute  the 
preliminary  step  in  the  formation  of  an  adhesion  (see  Fig.  256).  Organiza- 
tion of  the  mass  is  the  last  process,  and  by  some  is  considered  as  a  third 
stage.  Unless  the  inflammation  be  fulminatingly  rapid,  organization  has 
begun,  at  the  point  of  attachment  to  the  valve,  i>y  the  time  the  vegetation 
is  visible  to  the  unaided  eye ;  as  organization  progresses,  new  blood-vessels 
develop  from  the  base  of  the  valve,  are  projected  into  the  leaflet,  and 
finally  enter  the  vegetation  at  its    point  of    origin.      The  presence  of 


Kic.  255. — .\arkiiweu  Mitkai.  Okifice.  Showing  RtsuLTS  of  .\n- 
hesions  with  considerable  flbroid  thickening  (button-hole 
Mitral). 

dcs  and  tendons.  B  to  C.  .Arcn  of  .idhesinn 
/'  to  E.  Sciond  .irea  of  adhesion  and 
niafKin  of  the  valve  is  intensely 
indurated,  rcnderinK  the  leaflet  too  stitT  to  riose  rearlily  .ind.  as  a  ri- 
sult  of  the  .idhesions.  unal>le  to  o|ien  its  normal  lumen,  RJvinK  ris<-  lo 
Uith  stenosis  and  regurKitation.— (T^rom  specimrn  in  author's 
iiilUition  ) 


5IO 


SPECIAL   PATHOLOGY. 


sufficiently  active  pyogenic  and  some  other  bacteria  may  limit  or 
prevent  organization  and  give  rise  to  disintegration  and  softening. 

The  influence  of  these  changes  upon  the  structure  and  functions  of 
the  affected  valve  may  be  epitomized  as  follows:  (i)  At  an  early  stage 
the  thickening  or  swelling  muffles  the  valves  and  alters  the  sounds  pro- 
duced by  their  closure;  (2)  if  not  prevented  by  the  cap  of  fibrin  a  hole 
may  be  torn  in  the  valve' (fenestration),  or  traction  by  the  flowing  blood 
on  a  large  or  loosely  attached  vegetation  may  pull  it  away,  giving  rise 
to  a  fenestrum  at  the  point  from  which  the  fibrin  mass  was  detached; 

(3)  laceration  of  the  valve  leaflet,  a  further  process  than  fenestration; 

(4)  adhesions  of  valve  leaflets  (see  Fig.  256);  (5)  induration,  as  organiza- 
tion occurs;  (6)  contraction  of  the  valve  (see  Fig.  255);  (7)  calcareous 
or  atheromatous  changes  (see  Fig.  256);  (8)  dilatation  of  the  valve 
or  orifice  may  occur  early,  from  the  softening  and  edema  of  the  initial 
stage,  or  it  may  follow  the  atheroma;  (9)  a  single  valve  leaflet  may 
relax,  producing  what  is  sometimes  termed  an  aneurysm  of  the  valve. 

Acute  Malignant  Endocarditis.  ^ — (Synonyms,  Ulcerative,  Mycotic,  Bac- 
terial, or  Pustular  Endocarditis;  Arterial  Pyemia;  L' Endocardite  Vege- 
tante  Ulcereuse;   Endocarditis  Pycemica;  Diphtheric  Endocarditis ,  etc.) 

Causes. — -As  intimated  when  discussing  the  classification  of  endo- 
carditis, the  ulcerative  variety  possesses  no  causative  factors  that  dis- 
tinguish it  from  the  milder  form  just  described.  The  bacteriology  of 
the  two  conditions  is  essentially  similar,  although  in  cases  assuming  the 
virulent  type  pneumococcic,  streptococcic,  and  other  pyococcic  infections 
are  the  commonest.  The  disease  is  frequently  associated  with  pyemia, 
septicemia,  croupous  pneumonia,  puerperal  and  wound  infections,  ab- 
scesses, osteomyelitis,  and  other  processes  in  which  the  pyogenic  bac- 
teria are  usually  found.  The  simple  form  of  endocarditis  may  gradually 
develop  into  the  malignant  type.  Malignant  endocarditis  is  particu- 
larly prone  to  involve  the  sclerotic  valves;  Orth  holds  that  it  never 
affects  previously  sound  tissue,  and  the  number  of  cases  examined 
postmortem  in  which  the  acute  lesion  was  engrafted  on  sclerotic  leaflets 
differs  in  the  collected  series  of  cases,  but  is  always  high,  ranging  from 
sixty  to  eighty-eight  per  cent.  Occasionally  it  is  secondary  to  myo- 
cardial infection,  particularly  when  the  latter  results  from  infective 
embolism  of  the  coronary  artery. 

Ulcerative  endocarditis  may  affect  (i)  the  contact  line  of  tlie  valves, 
(2)  base  of  a  leaflet,  or  (3)  it  may  be  mural.  As  to  orifice,  Osier,  Sansom, 
and  Hamilton  accept  the  following  order:  (i)  Mitral;  (2)  aortic;  (3) 
aortic  and  mitral ;  (4)  heart-wall;  (5)  tricuspid;  (6)  pulmonary.  The 
valves  of  the  right  side  of  the  heart  are  more  frequently  affected  in 
this  form  of  endocardial  inflammation  than  in  the  acute  simple  endo- 
carditis. This  is  to  be  explained  by  the  fact  that  in  such  infectious  dis- 
eases as  suppuration,  erysipelas,  osteomyelitis,  puerperal  fever,  and  other 
infections  involving  the  genito-urinary  organs,  ulcerations  of  the  intes- 
tine, suppurative  processes  in  the  liver,  and  otitis  media,  the  venous  blood 
returns  to  the  heart  charged  with  the  bacteria,  and  hence  the  valves 

'  Herrick.  "Northwestern  Lancet,"  March  15,  1902.  Lenhartz,  "Miinch. 
med.  Woch.,"  July  9,  1901.  Robinson,  "Amer.  Jour,  of  Med.  Sci.,"  April,  1904, 
p.  623.  French,  "The  Practitioner,"  Dec,  1904,  p.  753.  Coleman,  "Amer. 
Jour,  of  Med.  Sci.,"  March,  1905.  Thorel,  "  Lubarsch  and  Ostertag's  Ergeb- 
nisse  d.  allgem.  Path.  u.  path.  Anat.,"  1903,  Neunter  Jahr.  I.  Abt.,  p.  718. 


VASCl'LAR  SYSTKM. 


5" 


first  subjected  to  the  danger  of  infection  are  those  of  the  right  side. 
Following  Virchow,  most  oV)servers  believe  that  the  infection  is  the 
result  of  direct  implantation  of  bacteria  upon  the  valve  segments, 
althoui,'h  Koster  has  strongly  urged  the  possibility  of  infection  through 
the  blood-vessels  of  the  leartet.  The  almost  com])lete  al»sence  of  blood- 
vessels in  the  normal  leaflet,  and  the  fact  that  bacteria  are  most  abundant 
in  the  periphery  of  the  lesion,  would  favor  the  view  rirst  given;  Roster's 
contention  is  supported  by  the  frequency  with  which  the  disease  affects 
valves  vascularized  as  the  result  of  antecedent  inflammation. 

Morbid  Anatomy. — Whether  preceded  by  simple  inflammation  or 
not,  necrosis,  ulceration,  and  loss  of  tissue  are  almost  constantly  present. 
Ulceration  in  the  sense  that  a  distinct  recognizable  or  anatomically 
perfect  ulcer  must  be  developed  is  not  at  all  necessary.  Bacteria  are 
invariablv  present  during  the  active  stage  of  the  process,  and  are  usually 
most  abundant  in  the  superficial  layers  of  the  vegetation,  although  they 
are  not  infrequently  present  at  the  bases  and  in  the  interstices  of  the 
valves.  Vegetations  are  usually 
large,  although  well-marked  cases 
have  been  reported  in  which  they 
were  small.  They  usually  manifest 
evidences  of  necrosis,  softening,  and 
fragmentation.  As  a  result  of  these 
changes,  embolism,  with  the  de- 
velopment of  suppurative  pro- 
cesses in  other  viscera,  usually 
accompanies  this  form  of  endo- 
carditis. The  necrotic  processes 
are  not  restricted  to  the  vegetation 
alone,  but  may  involve  the  affected 
leaflet,  which  is  sometimes  totally 
destroyed.  Mural  lesions  are  not 
infrequent ;  they  sometimes  depend 
upon  direct  inoculation  from  l)ac- 
teria  in  the  blood;  in  other  cases 
their  location  would  indicate  that 
the  vegetation  had.  by  contact,  in- 
oculated the  ventricular,  auricular, 

or  aortic  wall.  Cases  occur  in  which  it  is  possible  to  believe  that  the 
infection  involved  the  heart  muscle  as  a  result  of  dissemination  through 
the  blood  by  way  of  the  coronary  artery. 

Microscopic  abscesses  are  sometimes  to  be  recognized  in  the  valve 
tissue,  and  similar  areas  of  a  larger  size  are  occasionally  observed  in 
the  myocardium.  The  extension  of  the  infection  to  the  myocardium 
mav  lead  to  penetration  or  perforation  of  the  ventricular  septum,  aneu- 
rvsm,  or  rupture  of  the  heart.  The  calcific  deposits  occasionally  ob- 
served in  this  form  of  endocarditis  may  be  due  to  the  fact  that  the  lesion 
is  ingrafted  upon  an  old  endocardial  change  in  which  calcification  was 
present.  In  other  instances  there  is  reason  to  believe  that  the  infiltra- 
tion is  secondary  to  the  acute  process  with  which  it  is  found. 

The  structural  alterations  produced  by  this  form  of  endocarditis 
are  often  striking;  entire  leaflets  may  disappear  and  penetration  of 
the  cardiac  senta  ma\-  L'ive  rise  to  abnormal  communication  between  the 


Fig.  256. — Adjacext  Aortic  Cusps,  Showing  a 
Small    Vegetation-    Devf.lopisg   Jcst    Below 

THE  POIST  OF  A.V  OLO  .VdHESION. 

Calcareous  areas  are  indicated  by  the  white  areas  on 
the  valve  leaflet.  \  case  of  acute  en  'ocardial  in- 
flammation int;ratted  on  chronic  lesion. 


512  SPECIAL  PATHOLOGY. 

cavities.  The  disease  is  often  rapidly  fatal,  although  Herrick's  con- 
tention that  many  typical  cases  recover  is  now  generally  accepted. 
The  rapid  formation  and  prompt  necrosis  of  vegetations  induce  a  con- 
stant change  in  the  morphology  of  the  affected  valves  and  fibrin  masses, 
resulting  in  sudden  alterations  in  the  ph^^sical  signs,  usually  absent  in 
other  types  of  endocarditis.  In  some  cases  the  symptomatologv  is 
largeh^  restricted  to  the  heart  manifestations ;  this  form  of  the  affection 
is  called  the  cardiac  type.  In  other  instances  the  symptomatology  is  not 
unlike  typhoid  fever  {typhoid  type).  In  the  pyemic  or  septic  type,  the 
phenomena  are  those  of  pyemia  or  septicemia ;  embolism  and  metastatic 
abscesses  are  not  infrequent.  In  some  cases  definite  febrile  paroxysms, 
during  which  the  temperature  rises  sometimes  from  5°  C.  to  6°  C,  occur 
{pseudo malarial  type).  These  phenomena  are  due  to  the  influence  of 
bacterial  toxins,  derived  from  the  lesions  in  the  heart,  or  resulting  from 
the  pullulation  of  bacteria  in  the  blood-stream.  Septic  inflammations 
of  the  joints  are  not  uncommon;  endarterial  infection  which  may  ter- 
minate in  aneurysm,  and  rupture  of  the  affected  vessel,  sometimes 
occur;  these  and  other  indications  of  a  widely  distributed  infection 
justify  the  name  arterial  pyemia  given  to  the  condition  by  the  older 
writers.  Some  of  the  cases  belonging  to  the  cardiac  type  mav  drag 
along  for  weeks  or  even  months  (chronic  ulcerating  endocarditis) ; 
French  refers  to  an  instance  in  which  the  illness  lasted  297  days.  In 
the  cases  that  recover  there  is  usually  marked  valvular  distortion,  which 
may  also  involve  the  orifice,  permanently  crippling  the  heart. 

Chronic  Endocarditis. — (Synonyms,  Indurative,  Fibrous,  Sclerotic, 
Adhesive,  Interstitial,  or  Permanent  Endocarditis  and  Arteriosclerotic 
Valvulitis.) 

Chronic  induration  of  the  cardiac  valves  may  result  in  a  number  of 
conditions;  as  already  indicated,  the  acute  forms  of  endocarditis  may 
leave  the  valves  irreparably  damaged,  the  leaflets  thickened,  the  margins 
irregular  and  indurated  and  sometimes  adherent.  It  is  not  improbable 
that  minor  structural  alterations  in  the  leaflets  may  constitute  a  basis 
upon  which  a  chronic  sclerosing  process  is  implanted.  In  many  cases, 
however,  this  condition  occurs  without  any  antecedent  endocarditis. 
It  is  particularly  associated  with  affections  in  which  persistent  high 
tension  occurs.  Roy  and  Adami  showed  that  if  the  aortic  pressure 
be  raised  by  constriction  of  the  aorta,  edematous  blebs  might  develop 
in  the  aortic  leaflets  at  points  corresponding  to  the  location  of  the  most 
characteristic  lesions  of  chronic  fibroid  valvulitis.  It  is  probable  that 
this,  in  a  way,  explains  the  influence  of  increased  stress  on  the  valve 
leaflets  in  man.  The  hypertension  associated  with  arteriosclerosis  and 
contracted  kidney  is  a  frequent  cause.  This  form  of  valvular  disease 
is  often  seen  in  syphilitics  and  in  the  gouty,  and  is  common  in  alcoholics. 
Valvular  sclerosis  is  rare,  although  not  unknown,  in  youth,  and  occurs 
with  increasing  frequency  in  each  decade  after  the  fourth.  It  is  so  con- 
stantly associated  with  degenerative  changes  in  the  vessels  that  it  has 
been  called  arteriosclerotic  valvulitis. 

Morbid  Anatomy. — Chronic  sclerotic  changes  occur  in  both  mural 
and  valvular  endocardium;  in  the  former  the  change  is  rarelv  intense. 
The  valves  and  orifices  commonly  affected  are  those  of  the  left  side  of  the 
heart;  sclerosis  of  the  tricuspid  and  pulmonary  leaflets  is  exceedingly 
rare.     The  first  change  observed  is  a  grayish  opacity,  usually  developing 


VASCULAR   SYSTEM.  513 

along  the  line  of  contact  and.  on  the  aortic  leatlets,  often  radiating 
from  the  corpora  arantii.  Sometimes  the  thickening  forms  distinct 
lines,  parallel  with  the  free  edge,  giving  the  surface  of  the  valve  a  riy)- 
pled  appearance.  Occasionally  the  valves  remain  pliable,  constituting 
the  soft  variety  of  chronic  valvulitis.  Histologic  examination  of  such 
structures  shows  that  the  new  tissue  is  mostly  elastica;  this  type  is 
of  infrequent  occurrence  and  the  lesion  is  rarely  marked.  The  dense 
or  hard  form  is  more  common.  Histologic  examination,  in  the  earlier 
stages,  discloses  a  marked  connective-tissue  hyperplasia,  scantily  sup- 
plied with  fibroblasts.  The  interstitial  hbroid  change  develops  slowly, 
and  gradually  extends.  It  increases  the  thickness  and  lessens  the  plia- 
bilitv  of  the  valve,  sooner  or  later  contracts,  and  undergoes  calcareous 
change.  The  newly  formed  fibrous  tissue  freciuently  shows  necrotic  and 
degenerative  processes,  and,  when  fully  developed,  commonly  contains 
areas  of  calcareous  infiltration.  Degenerative  and  necrotic  changes  in 
the  overlying  endothelium  may  expose  the  calcareous  plaques;  the 
presence  of  projecting  spicules  of  calcific  matter 
leads  to  a  deposit  of  blood-platelets  followed  by  fibrin, 
so  that,  even  in  this  form  of  endocarditis,  small 
fibrinous  collections  (vegetations)  are  occasionally 
seen.  As  contraction  progresses,  curling  of  the 
valve  edges,  insufficiency,  and  stenosis  commonly 
develop.       In    figure    254   the    valve  leaflet   on   the 

extreme  right  is  beginning  to  show  slight   eversion.  

The  chordae  tendineae  thicken,  agglutinate,  or  shorten,     fig.  257.— .adherent 
so    that    the    muscle    may    appear    to    be    inserted  valve^leaflek. 

immediatelv  into  the  valve  cusp;    narrowing,   mar-  —(Rindfieisch.) 

ginal  thickening,  and  adhesion  lead  to  such  condi-     ^"'^'^^n^^-'^^iowm^rd 
tions  as  the  button-hole  mitral,  funnel   mitral,  etc.  up^^n    '"je^^aortk 

As  the  sclerosis  advances,  the  calcific  changes  become  aoru.   Two  leaf- 

more  marked,  and  eventually  the  valves  and  margins  !^^^re''con1rac5'cd; 

of  the  orifices  are  converted  into   hard,   calcareous.  thickened,  tverted. 

,,  .  ,  .    ,  ,  11  ,  .ind       unable       to 

tibroid  Structures,  with  scarcely  a  normal  element  re-  open    widdy    or 

maining.     The  mural  form  of  chronic  endocarditis  is  ''"'^ "^''''*- 

secondary  to  atheroma  or  interstitial  myocarditis,  and 
is  manifested  by  the  presence  of  hard,  fibroid,  or  calcareous  areas  on 
the  cardiac  wall. 

Results  of  Endocarditis. — ^When  the  valve  does  not  return  to  the 
normal,  which  in  rare  cases  may  occur,  the  changes  already  described 
lead  inevitablv  to  one  of  two  conditions  or  to  both. 

I.  Xarnnciiig,  Obstruction,  or  Stenosis. — This  condition  may  be 
brought  about  in  any  of  the  following  ways:  (a)  Vegetations  projecting 
into  the  lumen  when  the  valve  is  open;  (6)  stiffened  valves  that  do  not 
open:  (c)  contracted  valves  that  can  not  open,  but  subtend  the  orifice 
like  a  cord;  {d)  adherent  valves,  the  adhesions  preventing  opening; 
(f)  eversion  or  inversion  of  a  leaflet  either  as  a  part  or  as  a  whole;  (/)  a 
lacerated  leaflet  hanging  in  the  current;  (,s;)  contraction  of  the  orifice 
incident  to  a  circumferential  inflammation  at  the  base  of  the  valve,  or 
in  the  mitral,  the  free  margin;  {h)  loss  of  elasticity  of  the  orifice,  owing 
to  fibrous  or  calcareous  changes,  or  to  both,  without  of  necessity  con- 
tracting, but  being  inelastic,  is  practically  a  stenosis;  (i)  combinations 
of  these  processes. 


5^4 


SPECIAL  PATHOLOGY. 


2.  Insufjiciency  or  Incompetency  of  the  Valves,  Permitting  Regurgi- 
tation.— (a)  Valves  may  be  propped  open  by  a  vegetation;  (6)  valves 
may  be  too  stiff  to  close;  (c)  contracted  valves  can  not  close,  for  the 
same  reason  that  they  can  not  open;  (d)  inverted,  everted,  or  lacerated 
valves  can  not  close  the  orifice;  (e)  fenestra  below  the  line  of  contact 
permit  regurgitation ;  (/)  contraction  of  the  orifice  leading  to  wrinkling 
of  the  leaflets  is  by  some  supposed  to  be  a  cause;  (g)  relaxation,  dis- 
tention, or  dilatation  of  the  orifice  beyond  a  size  that  the  valve  can 
close.  This  condition  is  called  relative  insufficiency  and  may  be  due 
to  relaxation  of  the  opening  without  any  disease  of  the  endocardium. 

Influence  of  Stenosis  and  Instiffieiency  on  Cardiac  Work. — It  matters 
not  which  of  the  above  processes  occurs,  the  inevitable  consequence  will 
be  increased  work  for  the  heart,  and  this  must  lead  to  either  hyper- 
trophy or  dilatation.  It  is  not  possible,  in  the  space  available,  to  con- 
sider the  physics  of  the  normal  circulation,  with  which  it  is  presumed 
that  the  student  is  familiar,  nor  can  the  disturbance  brought  about  by 
stenosis  and  insufficiency  be  fully  reviewed.  It  is,  of  course,  evident 
that  either  of  these  conditions  affecting  the  orifice  through  which  the 
ventricle  is  normally  emptied,  more  profoundly  influences  the  func- 
tion of  that  structure  than  when  the  process  involves  the  orifice  through 
which  the  cavity  is  filled.  With  the  occurrence  of  aortic  stenosis  the 
work  of  the  left  ventricle  must  be  increased,  as  it  necessarily  requires 
more  force  to  deliver  loo  gm.  of  blood  through  an  orifice  50  mm.  in 
diameter  than  it  would  if  the  orifice  possessed  a  diameter  of  70  mm. 
Were  there  not  so  many  factors  to  be  taken  into  consideration,  it  would 
be  possible  theoretically  to  calculate  the  amount  of  increase  in  cardiac 
work  that  would  result  from  a  one-tenth  reduction  in  the  sectional  area 
of  the  aortic  orifice.  The  cardiac  work  is  also  increased  by  insufficiency 
or  regurgitation,  for  if  100  gm.  of  blood  has  been  delivered  into  the 
aorta  during  the  previous  systole,  and  if  25  gm.  returns  to  the  ventricle 
by  reason  of  insufficiency  in  the  aortic  valves,  the  ventricle  at  the  same 
time  receiving  its  normal  inflow  from  the  auricle,  it  must  be  apparent 
that,  in  order  to  assure  its  progress,  one-fourth  of  the  blood  is  being 
pumped  into  the  aorta  twice.  It  of  necessity  follows  that  the  heart  is 
doing  one-fourth  of  its  work  over,  which,  of  course,  implies  an  enormous 
increase  in  cardiac  labor.  The  same  hypotheses  applied  to  the  auricles 
would  not  yield  the  same  conclusions;  the  auricular  cavities  communi- 
cate directlv  with  their  respective  venous  systems,  so  that  the  venous 
system  of  the  side  in  question  must  always  be  considered  practically 
as  a  part  of  the  auricle.  Nevertheless,  it  is  evident  that  regurgitation 
through  the  mitral  orifice  must  increase  the  work  of  the  heart,  as  when 
the  left  ventricle  contracts,  a  part  of  its  force  loses  its  effectiveness 
through  the  fact  that  the  insufficient  mitral  permits  a  backward  flow  into 
the  auricle.  During  the  next  diastole  the  ventricle  should  receive 
its  normal  quota  of  blood  plus  the  blood  that  was  regurgitated  into 
the  auricle  through  insufficient  mitral.  This,  of  course,  means  in- 
creased work  for  the  ventricle.  Mitral  stenosis  acts  differently, — 
at  least,  when  marked, — as  already  referred  to  when  considering  local 
atrophy  of  the  heart.  (See  p.  488.)  In  the  presence  of  increased 
cardiac  work  brought  about  in  ways  that  have  just  been  mentioned, 
hypertrophy  or  dilatation  must  of  necessity  follow. 


VAScri.  \k  s^■s  Ti-.M.  515 

HVrERrRol'HV  AND  DILATATION. 

Hypertrophy—  Dilatation— 

Simple.  [  Simple. ] 

[Eccentric]  With  thickcninj;. 

[Concentric]  With  thinning'. 

Simple  hypertrophy  is  increased  weight  with  increased  functional 
power,  without  evident  alteration  in  the  size  of  the  cavity. 

Eccentric  hypertrophy  is  assumed  to  be  increased  weight,  with  in- 
creased (?)  functional  power  and  increased  cavity;  in  other  words,  it 
is  the  same  as  dilatation  with  thickening;  during  life  the  symptoms, 
if  any  presented  themselves,  were  those  of  dilatation  rather  than  hyper- 
trophy. 

Concentric  hypertrophy  is  assumed  to  be  hypertrophy  at  the  expense 
of  the  cavitv:  that  is,  increased  weight,  etc.,  with  diminution  in  the  size 
of  the  cavitv.  It  is  a  postmortem  change,  or  is  dependent  upon  the  con- 
ditions that  determine  death.  Allbutt  refers  to  it  as  a  "mythical  type" 
of  hypertrophv.  How  easily  one  may  be  misled  is  illustrated  by  the 
following  experiment : 

Obtain  three  bullocks'  hearts  immediately  on  slaughtering.  In 
one  heart  all  the  vessels  should  be  ligated  before  the  animal  is  bled  or 
the  vascular  svstem  opened;  let  the  second  heart  remain  empty. 
The  third  heart  is  to  be  distended  by  ligating  the  pulmonary  veins, 
sectioning  the  aortic  valves,  and  attaching  the  aorta  to  a  hydrant.  It 
is  best  that  all  the  hearts  possess  about  the  same  weight.  In  a  few 
hours,  when  rigor  mortis  has  ceased  to  act,  the  following  will  be  found: 
The  first  heart  is  an  example  of  hypertrophy  with  a  normal  cavity ;  the 
second,  hvpertrophv  with  diminished  cavity;  the  third,  hypertrophy 
^^•ith  increased  cavity.  As  death  may  arrest  the  heart  in  any  degree  of 
distention,  or  rigor  mortis  act  to  any  extent,  the  foregoing  conditions 
mav  all  be  found  in  any  hypertrophied  heart.  Simple  hypertrophy 
thereff>re  remains. 

Dilatation  with  thickening  is  admitted,  as  is  dilatation  with  thinning; 
but  simple  dilatation  implies  a  larger  cavity,  with  wall  of  normal  thick- 
ness, and  as  such  a  heart  must  weigh  more,  it  requiring  more  muscle 
to  surround  a  large  cavity  with  a  wall  of  a  given  thickness  than  a  smaller 
cavity,  as  the  normal,  the  condition  is  one  of  dilatation  with  increased 
weight  or  thickening. 

Causes  of  Hypertrophy  and  Dilatation. — Increased  work  with  abun- 
dant nutrition  is  followed  by  hypertrophy.  Overwork — that  is,  work 
beyond  the  nutrition  and  muscular  power  of  the  organ — leads  to  dila- 
tation. 7-1 

These  may  be  due  to  conditions  i>!lracardiac  or  extracardiac;  the 
former  is  sometimes  called  cardiopathy,  the  latter,  when  due  to  vascular 
influences,  is  known  as  eardiac  arteriopathy. 

Among  the  intracardiac  causes  are  included  those  valvular  lesions, 
alreadv  described,  which  persist  sufticiently  long  to  influence  materially 
the  amount  of  work  that  the  heart  is  called  ui)on  to  perform;  these 
include  both  obstruction  and  insufficiency.  There  has  also  been  de- 
scribed a  form  of  subvalvular  stenosis  characterized  by  narrowing  of 
the  aortic  area  of  the  ventricle  immediately  on  the  cavity  side  of  the 
aortic  orifice;   the  condition  is  called  suhvalvular  or  pre-aortic  stenosis  or 


5l6  SPECIAL   PATHOLOGY. 

siihvalvtdar  coistriction}  In  the  cases  reported  by  Shennan  and  Smart 
the  condition  was  associated  with  aortic  obstruction.  Myocardial 
sclerosis  is  sometimes  given  as  a  cause  of  cardiac  hypertrophy.  It  is 
probable,  however,  that  in  most,  if  not  all,  hearts  in  which  fibroid 
change  and  hypertrophy  are  concurrent  the  sclerosis  has  followed  the 
hypertrophy,  and  not  the  reverse.  Overstimulation  of  the  cardiac 
muscle  resulting  from  excessive  use  of  alcohol,  tea,  or  tobacco  is  also 
given  as  one  of  the  intracardiac  causes  of  hypertrophy;  it  is  presumed 
that  the  influence  of  these  agents  is  manifested  by  overstimulation  of 
the  motor  ganglia  of  the  heart  or  by  an  inhibiting  influence  on  the  regu- 
lating mechanism  of  the  organ. 

The  important  extracardiac  causes  increasing  the  work  of  the  heart 
are  usually  grouped  as  (i)  physiologic  and  (2)  pathologic.  The  physio- 
logic include  the  increased  work  demanded  in  individuals  performing 
hard  labor  and  in  athletes;  Cardiac  hypertrophy  is  usually  held  to  be  a 
phvsiologic  process  during  gestation.  There  has  been  considerable 
discussion  as  to  whether  either  of  these  factors  is  important  in  the  pro- 
duction of  cardiac  enlargement;  the  weight  of  authoritative  opinion 
seems  to  be  in  favor  of  according  them  a  certain  value,  which,  however, 
is  not  great.  The  most  important  of  the  pathologic  causes  are  the 
arteriopathies,  which  increase  the  blood-pressure.  These  include  nar- 
rowing or  hyperplasia  of  the  aorta,  arteriosclerosis,  and  especially  the 
latter  when  associated  with  chronic  interstitial  nephritis.  Pericardial 
adhesions,  and  other  forms  of  chronic  pericarditis,  necessarily  increase 
the  amount  of  work  demanded  of  the  heart.  In  addition  to  the  fore- 
going, there  are  instances  of  cardiac  hypertrophy  occurring  particu- 
larly in  infants,  and  often  congenital,  for  which  no  satisfactory  explana- 
tion can  be  given." 

Hypertrophy  of  the  left  ventricle  is  by  far  the  most  common,  but 
hypertrophy  of  the  right  occurs  not  infrequently.  Those  of  the  pre- 
ceding causes  that  may  here  act  are  apparent,  and  to  such  may  be 
added  :  ( i )  Rise  of  pressure  in  the  pulmonary  area  due  to  mitral  disease ; 
(2)  narrowing  of  the  pulmonary  blood-vessels,  as  in  congenital  stenosis 
of  the  pulmonary  artery;  reduction  in  the  vascular  area  of  pulmonary 
artery,  as  in  emphysema  and  interstitial  pneumonia;  (3)  valvular 
lesions  of  the  right  side;  (4)  tumors  and  aneurysms  pressing  upon  the 
pulmonary  artery. 

Morbid  Anatomy  of  Hypertrophy. — Hypertrophy  may  involve  the 
entire  myocardium  or  may  be  largely  restricted  to  the  wall  of  a  single 
cavity,  usually  the  left  ventricle.  When  the  entire  heart  is  involved,  the 
organ  is  both  lengthened  and  broadened.  Hypertrophy  of  the  auricle 
without  dilatation  rarely,  if  ever,  occurs.  When  the  wall  of  the  left 
ventricle  is  involved,  the  apex  of  the  heart  is  formed  by  the  myocardium 
of  that  side,  and  is  usually  displaced  toward  the  left.  Hypertrophy  of 
the  right  ventricle  broadens  the  heart  more  than  when  the  opposite  side 
is  involved;  the  lengthening  is  less  marked.  The  test  for  hypertrophy 
is  increased  weight;   hearts  weighing  over  1800  gm.  have  been  reported. 

1  See  Allbutt.  "A  System  of  Medicine,"  edited  by  Allbutt,  189S,  voL  v,  p. 
919.  Also  Shennan,  "Lancet,"  Jan.  7,  1905, p.  21,  and  Smart,  "Lancet,"  Nov. 
19,    1904,   p.    1417. 

2  Hedinger,  "Virchow's  Arch.,"  Bd.  178,  No.  2.  Simmonds,  "Miinch.  med. 
Woch.,"  Jan.  24,  1899. 


VASCULAR   SYSTKM.  517 

In  uncomplicated  hypertropliy  the  myocardium  it  often  redder  than  in 
health,  tirm.  and  resists  incision.  Frequently  there  is  an  associated 
fibroid  or  fatty  chancre,  in  which  case  the  muscle  is  paler  than  normal; 
if  fibroid,  the  density  is  increased;  if  fatty,  the  organ  is  soft.  Histo- 
logicallv  there  is  probably  a  numeric  increase  of  muscle  fibers,  and,  dur- 
ing the  active  stage,  both  the  new  and  the  old  fibers  are  larger  than 
normal. 

Life  History  of  Hypertrophy. — Hypertrophy  is  not  a  disease,  but  a 
definite  phvsiologic  process  with  the  distinct  object  of  meeting  a  demand 
for  more  cardiac  force:  just  as  any  muscle  responds  to  an  increased 
stimulus  for  energy,  the  heart  may  respond.  It  is,  however,  imperatively 
necessarv  that  the  demand  be  not  too  suddenly  developed,  and  that 
abundant  nutrition  be  supplied  to  attain  the  desired  end.  It  will  be 
observed  that  most  of  the  causes  already  given  are  progressive  in  char- 
acter and  permanent  in  action,  and  will,  therefore,  indefinitely  increase 
the  demand  for  work;  or  advancing  years,  with  the  concomitant  changes 
in  general  nutrition,  or  the  inroad  of  other  processes,  such  as  Bright's 
disease,  modifv  the  nutritional  value  of  the  blood  and  lessen  the 
available  food-supply  for  the  heart.  In  either  case  the  compensation 
that  nature  has  attempted  may  be  overthrown  by  the  wasting  that  the 
new  changes  induce.  In  the  earlier  stages  of  stenosis  and  insufti- 
ciencv  abundant  nutrition  and  slowly  increasing  work  favor  the  occur- 
rence of  hvpertrophy,  with  which  there  may  be  a  certain  degree  of  dila- 
tation. The  hypertrophy,  however,  exceeds  the  dilatation;  with  the 
increased  cavity  there  is  a  proportionate  increase  in  the  volume  of 
muscle.  Later",  dilatation  gains  on  the  hypertrophy,  compensation 
fails,  and  the  circulation,  possibly  for  the  first  time,  begins  to  manifest 
evidences  of  embarrassment.     Hypertrophy  then  passes  into  dilatation. 

Acute  dilatation/  or  dilatation  not  preceded  by  hypertrophy,  un- 
doubtedlv  occurs,  and  merely  shows  that  the  initial  nutrition  can  not 
supplv  the  initial  demand;  ordinarily,  this  is  met  by  the  reserve  force 
of  the  organ,  but  this  may  be  deficient  as  the  result  of  general  malnu- 
trition or  local  disease,  as  occurs  in  granular  degeneration  and  myo- 
carditis, or  the  work  suddenly  thrown  on  the  heart  may  be  beyond  the 
power  of  the  reserve  force;  in  either  case  the  inability  of  the  organ  fully 
to  perform  its  function  leads  to  a  gradual  accumulation  of  blood  within 
the  cavitv,  and  dilatation  results.  Acute  dilatation  occurs  in  mountain 
climbing,'  after  severe  exertion,  and  sometimes  during  excitement: 
suddenlv  developed  valvular  insufficiency,  as  from  laceration  or  rup- 
ture of  a  leaflet,  may  bring  about  the  same  result.  The  myocardium 
mav  vield  and  the  cavities  overdistend  under  the  influence  of  bacterial 
toxin's.  This  form  of  acute  dilatation  is  especially  observed  in  diph- 
theria, pneumonia,  rheumatic  fever,  typhoid,  influenza,  and  other 
infectious  diseases  characterized  by  toxemia.  In  some  of  these  con- 
ditions (diphtheria)  the  dilatation  develops  with  such  rapidity  as  to  cause 
practically  instantaneous  death.  Occasionally  the  myocardial  weakness 
comes  on' somewhat  insidiously  and  may  appear  during  convalescence: 
Clifford  Allbutt  has  particularly  called  attention  to  this  form  of  cardiac 
overdistention  following  typhoid  fever.     In  patients  exhausted  by  pro- 

•  De  la  Camp.  "Zeit.  f.  klin.  Med,"  vol.  51.  Nos.  i  and  2.  Stanley.  "Brit. 
Med.  lour.,"  Dec.  26,  1903,  p.  1636.  Menninger.  "Arch.  Schiffs-  und  Tropen 
Hvg.."  Nov..  1903.     Dawe  and  Austin,  "Lancet."  1904.  vol.  ii.  p.  49^^ 


5IO  SPECIAL  PATHOLOGY. 

tracted  illness,  such  as  tuberculosis,  or  profound  blood  dyscrasiee, — for 
example,  chlorosis,  pernicious  anemia,  and  leukemia, — a  moderate 
acute  or  subacute  dilatation  may  result  from  slight  exertion. 

Chronic  dilatation,  as  previously  mentioned,  usually  follows  hyper- 
trophy, when  compensation  can  no  longer  be  maintained. 

Morbid  Anatomy  of  Dilatation. — Most  common  on  the  right  side,  and 
most  marked  in  all  the  cavities  in  aortic  incompetency.  The  auricle 
never  hypertrophies  without  dilatation,  and  may  attain  an  enormous 
size.  Dilatation  of  a  cavity  leads  to  dilatation  of  the  orifices  that 
communicate  with  it,  and  hence  to  incompetency.  Opacity  of  the  endo- 
cardium has  been  noted.  The  muscle-fibers  not  uncommonly  show 
advanced  degenerative  change,  and  in  some  cases  a  well-defined  inter- 
stitial myocarditis  may  be  present.  Degeneration  of  the  cardiac  ganglia 
has  been  observed. 

Influence  of  Cardiac  Failure  on  the  Circulation  and  Nutrition  of 
Other  Organs. — Lesions  of  the  valves  or  orifices,  and  alterations  in 
the  texture  of  the  myocardium,  may  render  the  heart  unable  adequately 
to  propel  the  blood  onward,  in  which  case  accumulation  in  the  venous 
system,  distention  of  capillaries  within  organs,  chronic  congestion, 
malnutrition,  edema,  pigmentation,  and  other  conditions  follow.  In 
order  to  appreciate  the  extent  of  the  alterations  depending  upon  cardiac 
ineflficiency  it  is  necessary  to  consider,  briefly,  the  sequence  of  events 
resulting  from  disease  affecting  the  aortic  orifice;  for  present  purposes 
it  is  immaterial  whether  the  lesion  of  the  orifice  be  obstruction  or  re- 
gurgitation. In  either  case  the  increased  work  thrown  upon  the  left 
ventricle  will,  in  favorable  cases,  be  met  by  hypertrophy,  which,  under 
the  advancing  lesion,  becomes  inadequate,  the  myocardium  yields,  and 
dilatation  results.  AVhen  the  distention  of  the  left  ventricle  reaches  a 
certain  point,  the  valves  of  the  mitral  orifice,  if  not  already  involved, 
become  insufficient  because  of  the  increased  size  of  the  opening — relative 
insuflficiency.  This  condition  results  in  a  recoil  of  blood  into  the  left 
auricle  during  each  contraction  of  the  dilated  ventricle.  The  auricle 
now  receives  the  normal  quota  of  blood  coming  from  the  pulmonary 
veins,  and  also  that  regurgitating  through  the  mitral  orifice.  This  leads 
to  dilatation  of  the  auricle,  w^hich  may,  in  favorable  cases,  be  accom- 
panied by  slight  hypertrophy.  The  relatively  thin  wall  of  the  auricle  is 
not  equal  to  any  continued  stress,  and,  therefore,  the  hypertrophy  is 
rarely,  if  ever,  marked.  In  the  meantime  the  pulmonary  veins — the 
orifices  of  which  are  not  guarded  by  valves — encounter  the  blood  recoil 
resulting  from  the  relative  insufficiency  of  the  mitral;  the  increasing 
resistance  due  to  progressing  inefficiency  of  the  left  side  more  and  more 
influences  the  pulmonary  circulation,  first  by  raising  the  tension  of  the 
pulmonary  veins  followed  b}^  extension  into  the  capillaries,  and  eventu- 
ally the  pulmonary  arteries.  For  the  first  time  the  right  side  of  the  heart 
encounters  increased  tension  in  the  pulmonary  area,  and  must  therefore 
increase  its  capacity  for  work  or  yield  and  dilate.  Under  favorable 
conditions  the  wall  of  the  right  ventricle  hypertrophies,  raises  the 
pulmonary  tension  sufficiently  to  assure  delivery  of  the  requisite 
amount  of  blood  into  the  left  ventricle,  and  in  so  doing  subjects  the  pul- 
monary capillaries  to  the  deleterious  influence  of  persistently  increased 
tension.  Failing  nutrition,  and  continued  demand  for  force  beyond 
the  capacity  of  the  myocardium  of  the  right  wall,  lead  to  its  failure. 


VASCULAR  SYSTKM.  SIQ 

very  much  in  the  same  way  as  on  the  left  side.  The  resulting  dilata- 
tion of  the  right  cavity  causes  the  tricuspid  valves  to  become  inelHcient, 
regurgitation  occurs,   and  the  tension  in  the  systemic  veins  rises. 

In  the  meantime  the  congested  lungs  sutTer  from  the  haneful  influences 
of  a  flagging  circulation.  The  connective  tissue  and  clastiia'  increase,  here 
and  there  areas  of  circulatory  stasis  appear,  and  the  erythrocytes,  under 
the  influence  of  hemolysis,  disintegrate  and  yield  their  altered  pigment  to 
the  pulmonarv  parenchyma.  The  indifferently  nourished  bronchial  mu- 
cosa becomes  progressively  more  and  more  susceptible  to  infections,  and 
hence  chronic  bronchial  inflammation,  often  slight  but  usually  persistent, 
finds  a  permanent  abode  in  these  structures.  The  pigmentation  gives 
rise  to  a  brownish  color,  the  increase  in  interstitial  tissue,  and  the  bron- 
chial thickening,  render  the  lungs  firmer  than  in  health,  the  resulting 
condition  being  known  as  brown  induration.  The  sputum  contains 
leukocvtes  and  epithelial  cells  in  which  the  altered  pigment  is  often  pres- 
ent in  abundance.  While  the  condition,  just  described,  has  been  ])ro- 
gressing  in  the  lung,  important  structural  changes  have  been  taking 
place  in  other  organs.  Failure  in  normal  progression  through  the  right 
ventricle  necessarily  causes  a  rise  of  tension  in  the  larger  venous  trunks, 
and  this  in  turn  is  transmitted  to  the  capillaries  of  the  organs  drained. 
The  increased  capillary  tension  is  attended  by  changes  similar  to  those 
alreadv  described  as  occurring  in  the  lung.  In  the  liver  the  dilated  and 
distended  capillaries  increase  the  size  of  the  organ,  the  hemolytic  pro- 
cesses induce  pigmentation,  the  indifferent  nutrition  and  accumulation 
of  irritants  are  followed  by  connective-tissue  hyperplasia  (cirrhosis  of 
congestion),  and  degenerative,  necrotic,  or  atrophic  changes  give  rise  to 
wasting  of  the  parenchyma  cells  (red  atrophy);  all  of  these  combine  to 
render  the  hepatic  function  less  efficient  than  in  health.  As  the  capillary 
pressure  within  the  liver  rises,  the  portal  blood  encounters  increased 
resistance  within  the  hepatic  capillaries  and  the  consequent  tension 
is  transmitted  to  the  venules  and  capillaries,  the  confluent  branches 
of  which  form  the  portal  vein.  The  congested  spleen  increases  in  size, 
the  connective-tissue  content  of  the  organ  rises,  splenic  hemolysis 
increases,  and  pigmentation  of  the  parenchyma  progresses.  Such 
spleens  are  frequently  the  site  of  infarction.  Similar  influences  are 
manifested,  through  the  gastric  and  intestinal  veins,  on  the  capillaries  of 
the  intra-abdominal  alimentary  canal,  deleteriously  influencing  the  nutri- 
tion of  the  intestinal  mucous  membrane,  consequently  lessening  its 
secretory  and  absorbing  functions,  and  thereby  interfering  with  digestion 
and  attacking  nutrition  at  a  vital  point. 

While  the  tissues  drained  l)y  the  portal  circulation  are  undergoing 
the  changes  just  descril)ed,  the  increased  venous  tension  has  given  rise 
to  important  alterations  in  the  kidney.  Under  the  influence  of  the  rise 
in  venous  pressure,  and  consequent  capillary  slowing,  these  organs  de- 
velop changes  similar  to  those  that  have  been  described  in  the  lung, 
liver,  and  spleen.  The  renal  einthelium  is  ill-nourished,  the  connective 
tissue  proliferates,  the  consistence  of  the  organ  is  increased,  and  the  con- 
dition called  cyanotic  induration  is  gradually  produced.  The  fluid  out- 
put from  such  organs  may  not.  at  first,  be  altered  materially;  usually 
the  urine  is  increased  in  quantity.  Sooner  or  later,  however,  the  kid- 
neys become  unequal  to  the  task' of  secreting  the  toxic  substances  con- 
'  Pearce,  "PrDC.  of  the  Path.  Soc.  of  Phila.;"  July.  1901.  p.  215. 


520  SPECIAL  PATHOLOGY. 

tained  in  the  blood,  and  consequently  these  bodies  accumulate  in  the 
circulating  fluid. 

Cardiac  Edema. — The  rise  of  venous  tension  impedes  the  circulation 
in  the  extremities,  particularly  the  legs,  alters  the  endothelium  of  the 
capillaries,  and  eventually  gives  rise  to  edema.  This  same  tendency 
results  from  the  heightened  pressure  in  the  portal  circulation  inducing 
the  ascites  from  which  these  patients  commonly  suffer.  Transudates 
within  the  thoracic  serous  cavities  (hydro thorax  and  hydropericardium ) 
may  occur.  With  this  wide-spread  circulatory  disturbance  general  nu- 
trition suffers,  the  muscles  waste,  the  ability  to  combat  infections  is 
lessened,  and  the  patient  falls  a  prey  to  some  minor  infection,  pulmonary 
edema  and  infarction,  uremia,  or  other  legitimate  consequence  of  the 
circulatory  inadequacy. 

BLOOD-VESSELS.^ 
ARTERIES. 

The  normal  artery  is  composed  of:  (i)  Tunica  adventitia,  or  areolar 
sheath  of  fibrous  tissue.  (2)  Tunica  media;  (a)  in  the  larger  blood-vessels 
this  consists  of  elastica  and  resilient  fibrous  tissues  with  but  little  muscle- 
fiber;  (b)  in  the  arterioles  the  involuntary  fibers  predominate  and  but 
little  of  the  elastic  tissue  is  present,  (j)  Tunica  intiuia  is  histologically 
identical  with  the  endocardium,  and  is  known  as  the  endangium;  it 
lines  the  interior  of  all  the  blood-vessels  and  constitutes  the  wall  of  the 
capillary. 

Arteritis. — Inflammations  of  the  artery  may  involve  the  external 
coat  and  contiguous  tissues — periarteritis ;  the  internal  coat — endarter- 
itis; or  the  middle  coat — mesarteritis.  Many  of  the  conditions  ordi- 
narily described  as  inflammatory  and  grouped  under  the  term  arteritis 
are  composite  processes,  partly  degenerative  and  partly  inflammatory. 
In  other  instances  inflammatory  lesions  may  precede  degeneration  or 
degeneration  may  occur  in  the  cellular  accumulation  resulting  from  past 
inflammatory  processes. 

I.  Atheromatous  Arteritis. — (Synonyms,  Endarteritis  Chronica  No- 
dosa, Eiuiarteritis  Deformans.)  The  artificial  production  of  atheroma  by 
adrenalin  is  usually  construed  as  supporting  the  contention  that  the 
disease  is  due  to  hypertension.  The  affection  is  seen  particularh"  in 
connection  with  conditions  in  which,  at  some  time  or  another,  a  rise  in 
arterial  pressure  occurs.  It  is  not  certain,  however,  but  that  the  poisons 
giving  rise  to  the  hypertension  may  also  induce  degenerative  and  ne- 
crotic lesions  in  the  elastica,  which  is  always  involved.  This  form  of 
arteritis  has  been  thought  to  be  due  to  primary  sclerosis  of  the  vasa  vaso- 
rum.  The  condition  is  frequently  associated  with  chronic  interstitial 
nephritis,  syphilis,  gout,  and  rheumatism.  Overeating,  alcoholic  in- 
temperance, protracted  mental  stress,  and  excessive  sexual  indulgence 
are  accepted  as  causes.  The  disease  is  rare,  but  not  unknown,  in  the 
young ;  its  occurrence  increases  with  advancing  years  and  it  is  almost  in- 
variably present  in  adxilts  who  have  passed  the  half  century  mark.  The 
disease  appears  earlier  and  progresses  farther  in  men  than  in  women. 

*  The  important  literature  on  diseases  of  the  arteries  may  be  fovmd  in,  or 
traced  from,  article  by  Coplin,  "Proceed,  of  Path.  Soc.  of  Phila.,"  1904,  n.  s., 
vol.   vii,  No.   5,  p.    133. 


VASCULAR   ^V^  r  I-.  M 


:2i 


Morbid  Aiiaio»iy. — Atheroma  involves  particularly  the  larj^'cr  ves- 
sels, and  especially  the  arch  and  the  thoracic  and  abdominal  aorta,  in 
the  order  given.  All  of  the  larger  branches  of  the  arterial  tree  mav  be 
affected.  The  abdominal  branches  and  the  arteries  of  the  lower  limbs  are 
usually  more  susceptible  than  the  subclavian  and  its  branches.  The 
vertebral  and  larger  arteries  at  the  base  of  the  brain  are  not  infrequentlv 
affected.  It  is  particularly  prone  to  occur  around  smaller  branches  given 
off  by  larger  trunks;  at  such  points  it  gives  rise  to  elevated  rings  surround- 
ing the  lumen  of  the  afferent  vessel,  the  sectional  area  of  which  is  dimin- 
ished. By  reducing  the  blood-carrying  capacity  of  the  involved  vessels 
the  nutrition  of  the  organs  supplied  by  such  structures  is  necessarily 
affected.  Diffuse,  nodular,  and  linear  types  of  the  affection  have  been  des- 
cribed. The  first  manifestation  of  the  condition  consists  of  a  grayish  or 
milky,  semi-translucent  opacity  of  the  intima.  never  universal,  but  con- 
fined topatclie^  bore  and  there;  this  is  followed  by  elevation  of  the  patches, 


Fio.  258. — Heart  axd  Aorta  of  Rabbit,  .\i>rknalix  .\theroma,  and  Multiple  .\xedrysm.s. 
Part  of  the  left  ventricle  is  cut  aw.iy.     The  heart  shows  moderate  hypiTtrophy.     The  opened  aorta  is  the  seat  of 
the  following  lesions:   .1.  False  aneurysm  of  the  aorta  dissecting  in  the  media.     B.  Point  of  maximum  dila- 
tation; the  vessel  at  this  point  is  calcareous.     C.  Three  small  aneurysmal  sacs;  the  area  adjacent  is  calcareous. 
D.  Small  ancur>'5mal  sac  just  above  bifurcation  of  aorta.     (The  illustration  is  a  little  more  than  natural  size.) 


due  to  cellular  infiltration  and  thickening.  Fatty  changes  in  the  nodule 
give  rise  to  a  pale-yellow  spot  in  the  center,  wdiich  spreads  throughout 
the  entire  area  involved.  Deformity  of  the  vessel  is  manifested  by 
the  occurrence  of  button-like  elevations,  usually  most  marked  where  a 
branch  is  given  off,  and  irregular  dilations.  The  studies  of  Sailer  and 
Pf abler ^  indicate  that  the  vessels  are  elongated  as  well  as  dilated.  A 
central  necrosis  in  the  atheromatous  areas,  with  more  or  less  fatty  change, 
gives  rise  to  liquefaction.  This  may  terminate  by  involving  the  intima. 
which  exfoliates,  leaving  an  irregular,  so-called  atheromatous  ulcer; 
or  fibroid  and  calcareous  changes,  rarely  the  former,  with  absorption 
of  the  liquefied  part  of  the  mass,  may  perpetuate  the  condition  as  a 
fibrous  or  calcific  area,  corresponding  in  size  to  that  of  the  primary  infil- 
tration and  subsequent  necrosis.  Histologically  the  first  change  which 
I  have  been  able  t  >  detect  is  fragmentation  of  the  elastica  with  some 
'  "Amcr.  Jour,  of  Med.  Sci.,"  Oct..  ic)o.^.  p.  6i6. 


522 


SPECIAL  PATHOLOGY. 


swelling  between  the  fibers,  promptly  followed  by  the  accumulation  of 
mononuclear  cells  in  which  necrotic  and  degenerative  changes  give  rise 
to  Hquefaction.  The  process  terminating  in  the  formation  of  a  small 
cavity  containing  liquid  is  usually  referred  to  as  a  degeneration,  and  is 
regarded  by  some  observers  as  a  form  of  fatty  metamorphosis.     I  am 

convinced  that  it  is  a 
necrosis,  but  the  dis- 
tinction is  not  a  matter 
of  practical  importance. 
The  degeneration  com- 
mences near  the  media. 
The,  new  tissue  disinte- 
grates, forming  a  small 
cavity  filled  with  granu- 
lar debris,  oil  globules, 
and  occasionally  choles- 
terin.  Degeneration 
may  spread  to  and  in- 
vade the  media,  al- 
though extensive  in- 
volvement of  this 
stratum  is  not  .common. 
The  celkilar  infiltration 
of  the  arterial  wall  may 
be  first  manifest  or  most 
marked  a  r  o  xi  n  d  the 
branches  of  the  vasa 
vasorum. 

Atheroma  gives  rise 
to  loss  of  elasticity, 
weakening  of  the  wall, 
and  increased  liability 
to  aneurysm.  The 
arterial  tube  being  made 
rigid,  the  cardiac  work  is 
thought  to  be  increased, 
although  upon  this  point 
authorities  are  not  fully 
agreed. 

II.  Arteritis  obliter- 
ans^ is  observed  in  asso- 
ciation with  tertiary 
syphilis  and  contracting 
kidney,  and  is  present,  as 
a  local  process,  in  the 
vessels  supplying  areas 
of  tuberculosis.  Obliter- 
ative  changes  are  physiologic  in  the  vessels  of  the  fetus  which  become 

1  Bradford  and  Lawrence,  '"Jour,  of  Path,  and  Bact.,"  May,  iSgS,  p.  195. 
Gould,  "Lancet,"  March  15,  1902.  Morgan,  "Jour.  Amer.  Med.  Assoc,"  Nov. 
29,  1902,  p.  1359.  Branson,  "Path.  Soc.  of  London,"  Dec.  6,  1904.  Whitacre, 
"N.   Y.    Med.   Jour.,"   Jan.    28,    1905. 


Fig.  259. — .\oRTA,  Opened, 


Showing  Different  Types  of  .\th- 

EROMA. 

The  surface  is  most  extensively  altered  by  infiltration,  degeneration,  and 
necrosis.  Many  of  the  necrotic  areas  are  calcified  and  could  be 
fractured  by  bending.  A,  A,  A.  Elevated  obstructing  patches  of 
atheroma  surrounding  exit  points  of  small  branches.  B,  B.  Linear 
atheroma. 


VASCULAR  SYSTEM. 


523 


useless  at  birth,  and  in  the  arterial  supply  to  the  parturient  uterus,  after 
labor.  A  similar,  but  not  identical  process  occurs  in  the  branches  of 
ligated  vessels,  especially  those  not  i)articipatin},f  in  the  production  of 
any  succeeding  collateral  anastomosis. 

Morbid  A)iato»iy. — The  disease  is  y)rimarily  an  alTection  of  the 
smaller  vessels,  but  may  extend  centripetally,  producing  thrombosis  in 
the  larger  trunks.  The  affected  vessels  are  hard,  often  cord-like,  usually 
smooth  externally,  although  the  obliterating  7)rocess  is  rarely  symmetric 
internally.  Histologically  the  condition  is  characterized  by  extensive 
endothelial   proliferation   which   gradually  encroaches  upon   the  lumen 


Fig.  260. — Obi.itkkativk  Ksdartkritis.— (T/fc  lisxiif  jrom  whith  ilnrwiiig  -was  maile  U'lis  rcnunrd  jmm  iirar  a 

cancer  «j  the  jiuc.  mid  prcpured  in  Ihe  Inhoratory  oj  the  Jcjjerson  Medical  College  Hospital  by  Dr.  Tliomas  Leidy 

Rhoads.)     i-inch  ohjcctivc.  i -inch  ocular. 
Specimen  lixctl  in  corrosive  sutilini;ile,  infiltrateil  with  p;iraffin.  stained  with  hematoxylin  .and  eosin.  and  mounted 

in  balsam,     a.  .\dventitia.     b.  Media,     c,  c.  Ehislic  lamina,     d.  Irregularly  thickened  inlima.     The  gros.* 

specimen  was  hard,  cord-like,  but  not  ncxlular. 


and  at  the  same  time  greatly  thickens  the  vessel  wall.  It  is  not 
generally  believed  that  the  final  obliteration  of  the  vessel  results  from  a 
progressive  hyperplasia  of  the  intima,  but  that,  as  the  lumen  narrows,  a 
thrombus  forms,  completing  occlusion  of  the  artery.  In  specimens  that 
I  have  examined  there  was  rarely  any  conspicuous  alteration  in  the 
elastica.  In  some  cases  the  internal  elastic  lamina  is  reduplicated,  but 
this  I  have  often  observed  independently  of  vascular  disease.  The 
absence  of  changes  in  the  elastica  and  the  fact  that  degeneration  and 
necrosis    appear  never  to  involve  the    newly  formed  tissue  constitute 


524 


SPECIAL  PATHOLOGY. 


the    conspicuous  differences  between  this   affection  and  arteriosclerosis 
and  atheroma. 

The  obhterative  change  gives  rise  to  ischemia,  which  may  be  pro- 
gressive and  sometimes  terminates  in  gangrene.  In  the  case  reported 
by  Morgan  gangrene  occurred  in  the  four  extremities  and  necessitated 
amputation  of  both  legs  and  one  hand.  In  the  case  reported  by  Branson 
all  the  palpable  peripheral  arteries  were  indurated;  one  renal  artery  was 
involved  and  the  kidney  supplied  by  the  vessel  was  shrunken.  The 
figures  accompanying  Bradford's^  report  of  a  case  of  endarteritis  of  the 
renal  arteries  strongly  resemble  the  condition  under  consideration. 
The  reporter,  however,  does  not  call  it  an  instance  of  obhterative  end- 
arteritis ;  the  interlobular  arteries  were  thrombosed  and  the  cortex  of  the 
kidney  necrotic.  This  form  of  arteritis  may  be  associated  with  Reynaud's 
disease.  The  cause  of  the  obhterative  change  is  unknown ;  it  is  sometimes 
associated  with  svphilis,but  clearly  all  cases  are  not  of  syphilitic  origin. 

III.  Arteritis  infectiosa-  properly  embraces  all  of  the  infectious  dis- 
eases that  mav  involve  the  arteries.  It  is  customary,  however,  not 
to  include  tuberculosis  and  syphilis  in  the  group,  but  to  apply  the  name 
to  the  more  acute  inflammations  due  to  infectious  agents.  The  con- 
dition is  practically  always  of  bacterial  origin,  and  Gilbert  and  Lion 
have  shown  that  ^it  may  be  produced  experimentally  by  bacterial 
toxins.  As  an  affection  beginning  on  the  intima  it  is  nearly  always  the 
accompaniment  of  some  condition  attended  by  the  presence  of  bacteria 
in  the  circulating  blood.  In  such  cases  it  is  not  certain  whether  the 
infection  results  from  mural  implantation,  or  bacterial  embolism  of  the 
vasa  vasorum.  The  condition  is  of  frequent  occurrence  in  pyemia  and 
may  be  associated  with  ulcerative  endocarditis.  Thayer  has  especially 
studied  its  occurrence  in  typhoid  fever,  and  it  is  known  to  be  present 
occasionally  in  pneumonia,  influenza,  puerperal  fever,  and  other  infectious 
diseases,  including  gonorrhea.  Guyot  maintains  that  the  rheumatic, 
goutv,  diabetic,  and  even  the  arteriosclerotic  endarteri tides  are  really 
of  infectious  origin.  In  other  cases  the  affected  vessels  are  involved  as 
a  result  of  periarterial  disease,  such  as  abscess  and  other  suppurative 
conditions  contiguous  to  the  arteries. 

Morbid  Anatomy. — In  the  tmiral  variety  of  infectious  arteritis  the  in- 
itial lesion  is  in  the  intima,  the  endothelium  of  which  roughens,  followed 
bv  implantation  of  platelets  and  a  deposit  of  fibrin.  This  rapidly  con- 
verts the  lesion  into  a  thrombo-arteritis,  and  the  subsequent  manifesta- 
tions are  those  of  thrombosis  and  embolism. ^  The  interstitial  variety 
may  be  due  to  extension  of  the  mural  form,  infection  of  the  media  by 
the  vasa  vasorum,  or  involvement  of  the  vessel  wall  from  the  exterior. 
In  these  cases  leukocytic  infiltration  is  often  marked  and  softening  of 
the  vessel  may  lead  to  rupture  or  to  the  development  of  an  aneurysm. 
When  infection  involves  the  artery  by  extension  from  a  contiguous 
tissue  the  resulting  lesion  is  called  secondary  arteritis,  and  partakes  of 
the  essential  features  of  the  inflammatory  process  which  caused  it. 

^  "Jour,  of  Path,  and  Bact.,"  May,  1S98,  p.  195.  .      _ 

2  Hoist,  "Norsk  Magazin  for  Laegevidenskaben, "  April,  1901.     Coplm,      Pro- 
ceed, of  Path.  Soc.  of  Phila.,"  Mav,  1904,  p.  133.     Witte,  "  Zieg.  Beitr.,"  1905,  Bd. 
37,  H.  I.     Guvot.   "L'Arthritis,  Maladie  generale,  Microbienne  et  Transmissible, 
2   ed.,  Paris,    1905.     Allbutt,   "Lancet,"  July   18,1903,  p.  139.     Thayer,    "Bull, 
of  Johns  Hopkins  Hospital,"  Oct.,  1904. 

^  See  pp.   270  and  27S;    also  examine  Fig.   146,  p.   274. 


VASCULAR   SYSTEM.  525 

IV.  Endarteritis  Verrucosa,  or  \\\uiy  Endarteritis,  is  a  rare  condi- 
tion, and  probably  results  from  the  organization  of  thrombi  on  the  wall 
of  the  vessel;  it  usually  atTccts  the  larger  vessels — the  aorta  or  the  iliac 
or  femoral  arteries. 

Morbid  Anatomy. — Smooth  warty  growth  on  the  interior  of  the  vessel, 
the  same  color  as  the  intima,  and  jirojecting  into  the  lumen.  The  mass 
is  at  first  composed  of  young  cell  elements,  and  later,  for  the  most  part, 
of  fibrous  tissue  covered  by  endothelium. 

V.  Periarteritis  Simplex  {Charcot)  is  a  non-suppurative  condition 
affecting  the  vessels  of  the  brain,  and  leading  to  miliary  aneurysm. 
While  the  cause  is  not  established,  syphilis  seems  able  to  induce  the 
change.  It  first  attacks  the  adventitia  as  a  small  cell  infiltrate,  which 
invades  the  media  later,  and  the  intima  last,  if  at  all.  The  softening 
weakens  the  vessel  and  leads  to  aneurysm.  The  disease  is  most  common 
in  the  smaller  arteries,  but  may  invade  the  capillaries  or  the  larger  arteries 
of  the  base. 

VI.  Periarteritis  Nodosa.' — This  condition  has  been  described  as 
occurring  in  the  vessels  of  the  heart  (coronary  artery),  stomach,  kidney, 
spleen,  and  muscles.  As  a  rule,  the  smaller  vessels  alone  are  involved. 
Macroscopically,  the  irregular  nodular  enlargements  vary  in  size  from 
I  or  2  mm.  in  the  smaller  vessels  to  0.5  cm.  in  the  larger.  It  has  been 
thought  that  the  affection  did  not  involve  the  blood-vessels  of  the 
brain,  but  recent  studies  by  Schrotter-  would  indicate  that  the  cerebral 
vessels  may  be  affected.  The  vessels  are  dilated  in  some  areas,  and 
at  other  points  contracted.  An  abundant  cellular  infiltration  occurs 
in  the  outer  coat  of  the  vessel;  the  media  becomes  fatty,  but  the  intima 
is  not  affected.  The  small  sac-like  dilatations  not  uncommonly  contain 
clots. 

VII.  An  endarteritis  cartilaginosa^  has  been  described.  The  lesion 
is  obliterative  in  character  and  affects  particularly  the  intracranial  ar- 
teries. The  intima  and  media  may  be  slightly  infiltrated  by  mono- 
nuclear cells;  the  conspicuous  change,  however,  is  the  encroachment 
upon  the  lumen  by  tissue  consisting  of  a  hyaline  matrix  in  which  are  cells 
indistinguishable  from  those  of  cartilage — some  resembling  chondro- 
blasts — and  associated  with  the  presence  of  more  or  less  fibrous  tissue. 

Arteriosclerosis.'* — Under  the  name  arteriosclerosis  have  been  con- 
sidereil  a  number  of  conditions,  either  associated  or  occurring  indepen- 
dently. Many  writers  on  the  subject  have  grouped  the  lesions  already 
described,  and,  by  reason  of  the  fact  that  they  are  occasionally  associated, 
assumed  that  they  were  but  different  expressions  of  a  general  process. 
Gull  and  Sutton  apparently  intended  to  restrict  the  process  to  changes 

'  Schreiber,  Inaug.  Diss.  KOnigsberg.  1Q04.  Veszpremi  and  Joneso,  "Zie- 
gler's  Beitr.,"  1903,  Bd.  xxxiv,  p.  i.  Ferrari,  "Zicgler's  Beitr.,"  1903,  Bd.  xxxiv, 
P-  350. 

'■■^^iener  klin.  "Wochcn."  .-Vpril   15,   1899. 

'  MarVmrg.  "Centralbl.  f.  allgem.  Path.  u.  path.  .\nat.,"  1902,  Bd.  xiii. 

*  Coplin,  '■  Proc.  Path.  Sue.  of  Phila..  "  May,  1904,  n.  s..  vol.  vii,  p.  133.  Josue. 
"La  Presse  Mtd.."  .May  4.  1004.  ]•.  2S1.  Furst,  "Wien.  med.  Presse,"  Dec.  18, 
1004.  Ribbert.  "Centralbl.  f.  allgem.  Path.  11.  path.  Anat.,"  Dec.  31,  1004,  p. 
003.  Savill,  "Trans.  Path.  Soc.  01  London,"  1904,  vol.  Iv.  p.  37^.  Rzcntkowski. 
"Berl.  klin.  Woch.."  1904,  No.  31.  Prym,  "Virchow's  .Arch..^'  1004.  Bd.  177, 
p.  485.  lores,  "Virchow's  -Xrch.."  IQ04,  Bd.  17S,  p.  367.  Ehlers,  "Virchow's 
Arch,"  1904,  Bd.  178.  p.  427.  Sawada,  "Deut.  med.  Woch.,"  1904,  p.  425. 
Dunin.  "Zeit.  f.  klin.  .Med  ."   1904.  hi.  Nos.   5  and  6- 


526 


SPECIAL  PATHOLOGY 


in  the  capillary  and  arteriole  walls  associated  with  an  increase  in  fibrous 
tissue;  to  this  condition  they  gave  the  name  of  arteriocapillary  fibrosis. 
As  the  clinical  studies  of  the  affection  were  extended,  it  was  observed 
that  atheroma,  periarteritis  simplex,  etc.,  were  not  infrequently  asso- 
ciated with  changes  in  the  arterioles  and  capillaries.  This  led  to 
grouping  all  these  conditions  under  the  one  term — arteriosclerosis. 
Thoma  concluded  from  his  studies  of  the  process  that  it  was  not  to  be 
restricted  to  the  arteries,  but  that  it  involved  the  whole  circulatory  ap- 
paratus, and  hence  he  termed  the  condition  angiosclerosis.  Having 
considered  the  changes  observed  in  atheroma,  arteritis  obliterans,  and 
the  forms  of  periarteritis,  an  idea  may  be  formed  as  to  what  is  meant  by 
arteriosclerosis.  In  the  clinical  sense,  it  is  assumed  that  all  of  the  fore- 
going are  but  different  manifestations  of  the  same  process. 


1*^ 


K^ 


k^ 


Fig.  261. — Coronary  Artery,  Showing  Arterial  Sclerosis. 
A.  Adventitia.     B.  Media.     C.  Intima.     D.  Degenerating  newly  formed  tissue  which  at   E  shows  advanced 

softening. 

Old  age  is  said  to  be  one  of  the  causes ;  the  presence  in  the  blood  of 
the  poisons  of  gout  and  rheumatism,  and  of  the  irritant  bodies,  whatever 
they  may  be,  which  induce  chronic  interstitial  inflammation  of  the  kid- 
ney are  important  factors.  The  excessive  use  of  nitrogenous  food,  the 
abuse  of  alcohol,  poisoning  by  lead  (chronic  form),  and  the  poison  of 
syphilis  are  active  causes. 

That  atheroma,  obhterative  changes,  and  arterial  degenerations  are 
largely  due  to  increase  in  the  blood-pressure  is  indicated  by  the  fact 
that  under  normal  conditions  the  pulmonary  artery  is  rarely  involved, 
but  in  mitral  stenosis,  with  increased  intravascular  tension  in  the  lung 
and  marked  rise  in  the  blood-pressure  of  the  pulmonary  artery,  the  vessel 
not  infrequently  shows  atheroma;   and  in  cases  in  which  the  right  ven- 


VASCULAR  SYSTEM.  527 

tricle  hypertrophies,  and  thereby  further  raises  the  pressure,  atheroma 
may  be  widely  distributed  in  the  pulmonary  artery  and  its  branches. 
Exactly  what  raises  the  blood-pressure  of  the  left  side  is  not  always 
easily  determined.  The  method  by  which  it  is  raised  is,  of  course,  more 
readily  comprehended.     Thus,  if  it  be  assumed  that  the  heart  increases 


Fig.  262. — .Vrtery,  Early  Stage  of  .\rtf.riosclerosis. 
Stained  especially  for  the  demonstration  of  the  elastica;  Weigert's  method,  followed  by  Mayer's  carmalum  and 
picroindulin.  .1.  Broken  and  curled  elastica  which  at  places  shows  fraumcntation.  B.  Fibrohyaline  thickening 
of  the  intima:  within  this  stratum  can  be  seen  short  crinkled  fragments  of  elastica  that  have  been  regarded 
by  some  authors  as  efforts  at  regeneration.  Fragmentation  of  the  clastic  lamina  lis  particularly  marked 
just  above  the  leader  from  letter  B.  The  media  in  this  vessel  appears  much  broader  than  normal,  but  it 
is  most  difficult,  if  not  impossible,  to  say  that  it  is  hypx^rtrophied. 


Fig.  263. — .\rtery.  .\rteriosclerosis. 
Stained  especially  for  the  demonstration  of  the  elastica; 
Weigert's  methixl.  followcil  l>y  carmalum  and 
picroindulin.  .-1.  Fragmented  and  separated  elas- 
tica. B.  F'ragmentefl  and  curled  |clastica;  note 
the  swelling  of  the  isolate*]  fragment  and  the  curled 
end  at  B.  C.  Unusuiilly  crinkled  elastica  resulting 
from  vielding  and  recoil  due  to  solution  in  con- 
tinuity at  A  and  B.  D.  From  just  below  the  leader 
from  D  to  upper  part  of  drawing  there  is  no  break 
in  the  elastica.  It  will  be  ot»cr\e<l  that  in  that 
part  of  the  vessel  still  possessing  a  practically  nor- 
m.iJ  elastica  there  is  no  thickening  of  the  intima  and 
subintimaJ  stratum,  while  the  are.i  of  altered 
da.stica  is  ovcrl.aid  by  a  fibrohyaline  newly  formed 
tissue  containing  bits  of  elxstic  tissue.  There  is 
some  fragmentation  of  the  cxtern.il  ehustic  lamina 
which  is  present  in  this  specimen  l>ut  absent  from  the 
arteries  from  which  Figs,  j^i  and  j'j4  were  made. 


V'  il}  •!: 


t^iit^ 


Fic.  264. — .\rtery,  .-Vdva-nted  .■Vrterioscxerosis. 
Stained  especially  for  the  demonstration  of  the  elastica; 
Weigert's  method.  followc<l  by  carmalum  and 
picroindulin.  In  this  specimen  little  more  than 
irregular  fragments  of  the  elastic  lamina  are  pres- 
ent. The  endothelium  no  longer  forms  a  sep- 
arate layer,  but,  as  the  result  of  proliferative 
changes,  the  inner  stratum  is  composed  of  young 
connective-tissue  cells.  There  mav  lie  some  doubt 
as  to  whether  this  vessel,  iluring  life,  transmitted 
blood. 


its  outj)ut  of  l>lood  into  the  aorta,  and  at  the  same  time  there  is  no 
yielding  in  the  arterioles  throughout  the  body,  the  arterial  tension  must 
rise.  On  the  other  hand,  if  the  heart  continue  its  normal  output,  and 
there  be  contraction  of  the  arterioles,  a  similar  rise  in  pressure  must  be 
brought  about.     That  heightened  tension  has  something  to  do  with  the 


528  SPECIAL  PATHOLOGY. 

evolution  of  arteriosclerosis  is  indicated  by  possible  experimental  pro- 
duction in  animals  of  lesions  resembling  those  observed  in  this  form  of 
arterial  disease  in  man.  (See  Fig.  258,  p.  521.)  Dunin  has  found  that 
in  fully  developed  clinical  arteriosclerosis  the  blood-pressure  may  be 
below  normal;  prior  to  the  occurrence  of  degenerative  changes  in  the 
myocardium  the  tension  is  usually  above  the  normal,  and  when  intersti- 
tial nephritis  is  present  the  arterial  pressure  is  frequently  extremely 
high,  sometimes  reaching  250  mm.  of  mercury. 

Morbid  Anatomy. — In  describing  arteriosclerosis  it  may  be  assumed 
that  if  atheroma  be  properly  a  part  of  the  affection,  which  I  am  in- 
clined to  doubt,  it  is  a  late  manifestation.  My  own  observations,  and 
they  are  supported  by  the  studies  of  Jores,  have  led  to  the  conviction 
that  the  initial  change  is  in  the  elastica,  particularly  of  the  smaller  ar- 
terioles. In  the  earliest  stage  the  internal  elastic  lamina  is,  at  points, 
broken,  and  often  distinct  intervals  can  be  observed  between  the  ends 
of  severed  fibers.  In  such  areas  edema  and  mononuclear  infiltration 
quickly  appear,  followed  by  the  formation  of  new  connective  tissue  inter- 
calated between  the  elastic  lamina  and  the  endothelium  of  the  vessel. 
Later  the  fragraentation  of  the  elastica  becomes  still  more  marked  and 
the  encroachment  upon  the  vessel  lumen  by  the  newly  formed  tissue 
progressively  advances.  In  the  young  proliferate  and  in  the  area 
occupied  by  the  normal  elastic  lamina  there  appear  innumerable  fine 
fibrils  which  elect  the  elastica  stain;  these  are  evidently  of  recent  pro- 
duction, and,  while  others  speak  with  confidence  of  their  origin,  I  can 
not  say  with  certainty  whether  they  are  formed  from  the  new  cells  or 
from  the  pre-existing  elastica.  Analogy  would  justify  the  assumption 
that  the  latter  explanation  is  the  correct  one.  The  different  changes  in 
the  elastica  are  represented  in  figures  262,  263,  and  264.  This  somewhat 
immature  fibrous  tissue  matrix,  containing  the  irregularly  distributed 
elastica,  evidently  constitutes  the  hyalofibrous  tissue  recognized  by 
Gull  and  Sutton  as  present  in  the  walls  of  the  arterioles.  The  encroach- 
ment on  the  lumen  of  the  vessel  lessens  the  sectional  area  and  diminishes 
the  amount  of  blood  which  it  is  able  to  transmit ;  this  results  in  starva- 
tion of  the  tissue  beyond.  Savill  has  strongly  urged  that  there  is  a  dem- 
onstrable increase  in  the  muscle  of  the  affected  vessel,  and  clinical  phe- 
nomena (angina  pectoris,  arteriosclerotic  colic,  intermittent  claudica- 
tion) indicate  that  sclerotic  arterioles  may  be  spasmodically  contracted. 
I  believe  it  was  first  suggested  by  Hippolyte  Martin  that  atheroma 
might  depend  upon  arteriosclerotic  changes  in  the  vasa  vasorum,  and 
possibly  this  is  the  case. 

The  Influence  of  Arteriosclerosis  on  the  Nutrition  of  Organs.^ — The 
weight  of  the  brain  is  diminished,  the  nerve  cells  degenerated,  the  vessels 
tortuous,  and  in  some  cases  miliary  aneurysms  are  present;  degen- 
erative changes  have  been  described  in  the  ganglion  cells  of  the  cortex. 
In  the  spinal  cord,  perivascular  sclerosis,  which  is  usually  slight,  and 
degenerative  changes  in  the  motor  cells  have  been  observed  Inter- 
stitial'fibroid  change  in  the  peripheral  nerves,  associated  with  sclerosis 
of  the  nutrient  vessels,  has  been  described.  I  have  already  referred  to 
myocardial   changes  produced  by   sclerosis   of  the   coronary   arteries. - 

'  For  changes  in  the  nervous  system,  see  Spiller,  "Proc.  Path.  Soc.  of  Phila.," 
May,  1904,  p.  156.  Changes  in  the  gastro-intestinal  tract,  see  Longcope,  ibid., 
p.   165. 

^  See  Fibroid  Myocarditis,  p.  495. 


VASClT.Ak 


529 


An  arteriosclerotic  cirriiosis  of  tlie  liver  has  been  descnbeii,  but  it  is 
]>robable  that  the  fibroid  liver  and  vascular  chani^es  are  coincident  and 
due  to  the  same  cause,  and  that  the  hepatic  induration  is  not  the  result 
of  the  vascular  lesion.  Upie's  studies  indicate  that  there  may  be  some 
connection  between  arteriosclerosis  and  chronic  chanj^jes  in  the  pancreas, 
and  the  frequent  association  of  diabetes,  pancreatic  disease,  and  sclerotic 
vessels  supports  this  view.  It  has  been  sui^'ijested  that  gastric  ulcer 
may  be  of  arteriosclerotic  origin.  A  form  of  intestinal  colic  has  been 
attributed  to  sclerosis  of  the  mesenteric  vessels.  The  most  important 
visceral  lesion  accompanying  arteriosclerosis  occurs  in  the  kidney. 
This  condition  will  be  considered  later.' 

Tuberculosis-  of  the  arteries  is  rarely,  i)robably  never,  a  primary 
affection.  It  usual!}-  results  from  extension  of  a  tuberculous  process 
from  some  contiguous  tissue,  commonly  a  caseous  lymph-node,  in 
which  case  the  arterial  wall  is  gradually  infiltrated  from  without, 
eventually  giving  rise  to  a  cellular  accumulation  on  the  intima  in  which 
the  histologic  structure  of  tuberculosis  can  readily  be  recognized.  By 
infection  from  the  blood-stream  multiple  nodules  of  endarteritis  tuber- 
culosa may  be  produced.  These  may  consist  of  minute  granulations  or 
even  warty  growths  of  some  size,  and  are  usually  accompanied  by  miliary 
tuberculosis,  of  which  they  are  not  necessarily  the  cause.  The  endarter- 
ial  caseous  nodules  produced  by  the  intiltrating  tuberculosis  are  almost  in- 
variably followed  l)y  the  eruption  of  acute  miliary  tubercles  in  the  organs. 

Syphilis^  of  the  vascular  system  has  been  made  to  include  practically 
all  forms  of  arterial  disease.  The  poison  of  lues  is  generally  accredited 
with  ability  to  produce  almost  any  of  the  chronic  arterial  inflamma- 
tions and  degenerations.  Atheroma  and  arteriosclerosis  are  common 
manifestations  of  tertiary  syphilis.  Hiibner  described  an  endarteritis 
luetica  characterized  by  the  formation  of  fibrous  tissue  in  the  intimal 
and  subintimal  layer,  w'hich,  by  progressive  narrowing,  might  occlude 
the  affected  vessel.  In  the  nodular  form  of  this  affection  the  resem- 
blance of  the  endarterial  proliferate  to  gumma  may  be  striking.  Baum- 
garten  studied  a  similar  process  affecting  the  adventitia,  involving  the 
vasa  vasorum  and  thereby  infiltrating  the  media;  the  new  tissue  par- 
took of  the  characters  usually  observed  in  gummata.  In  the  cerebral 
arteries,  less  frequently  elsewhere,  a  distinct  gummatous  arteritis  some- 
times occurs.  Clinicaily  the  influence  of  syphilis  in  the  production  of 
aneurysm  is  commonly  recognized.  The  poison  of  syphilis  induces  struc- 
tural changes  in  the  elastica,  lessens  the  resilience  of  the  vessels,  and 
predisposes  to  dilatation  and  rupture.  To  such  forms  of  syphilitic  dis- 
ease of  the  Mr.oil-vessels  Mott  would  apply  the  term  ectasial  arteritis. 

Calcification^  of  blood-vessels  occurs  (i)  as  a  result  of  atluromatous 

*  See  Chronic   Interstitial   Nephritis. 

'  See  foot-note.  p.  154.  Also  consult  Blumcr.  "  Aincr.  Jour,  of  Med.  Sci.."  1890. 
vol.  cxvii.  Bernard  and  Salomon.  "Revue  de  Med.."  1905,  No.  i,  p.  45.  Witte, 
"Beitr.  z.  allg.  Path.  u.  path.  Anat.."  1004,  Bd.  ,^6,  p.  192.  Thorel.  "Lubarsch 
and  Ostcrtag's  Ergebnisse  d.  allg.  Path.  u.  path.  Anat.,"  Neunter  Jahrg.  I.  Abt. 
190.^.    p.    1039. 

'  Fahr.  "Virchow's  Arch.,"  1904.  Bd.  t;;.  p.  50S.  During.  "Dcut.  med. 
Woch.  ■  Dec.  15.  igo4.  Abramow.  "Virchow's  Arch.."  1904.  Bd.  17.S,  p.  406. 
Thorel.  "Lubarsch  and  Ustertag's  Ergebnisse  d.  allg.  Path.  u.  path.  Anat.,"  Neun- 
ter Jahrg.   I.  Abt.    1003.  p.   1042. 

*  Monckberg.  "Virchow's  Arch.,"  1903,  Bd.  171.  V.inz»-tti  ■  r.inrn.ilr  AfUa 
R.  Accad.  di  Med.  di  Torino,"  July  and  Aug.,  1903. 


530 


SPECIAL  PATHOLOGY. 


endarteritis  or  other  inflammation  of  the  vessel;  (2)  when  hme  salts 
are  deposited  in  the  vascular  wall,  without  any  discernible  antecedent 
disease,  the  condition  is  called  cryptogenic  calcification. 

Ossification,  or  true  bone  formation,  is  said  by  Orth  to  be  a  possi- 
bility; exactly  what  induces  it,  or  how  it  may  be  brought  about,  is  not 
known. 


Fig.  265. — Thoracic  Aneurysm. 
X  2  -K  Points  at  which  an  inserted  trocar  failed  to  reveal  the  presence  of  fluid  blood.  At  4  fluid  blood  was  found. 
'  '  At  the  autopsy  a  globular  aneurysm  17.';  cm.  in  diameter  was  found.  The  sac  bulged  between  the  "Tst  and 
fifth  ribs  the  second,  third  and'fourth  ribs  having  been  absorbed  in  front  of  it.  The  sac  was  hned  by  a 
laminated  clot,  s  cm.  thick,  internal  to  wluch  was  a  coagulum,  7  cm.  m  thickness.  The  aneurysm  com- 
municated with  the  arch  of  the  aorta,  and  had  been  treated  by  wiring.  (For  the  use  of  this  illustration  1  am 
indebted  to  Dr.  W.  \V.  Johnston,  Washington,  D.  C,  who  reported  the  case  in  'American  Medicine,  May 
II,  1901,  vol.  i.) 

Hyaline,  vitreous,  or  diaphanous  degeneration,  allied  to  that  form  of 
degeneration  described  by  Zenker  as  occurring  in  the  muscles,  has  been 
found  in  the  vessel-walls,  usually  in  the  arterioles.     (See  p.  247.) 

Amyloid  infiltration  has  been  considered  when  dealing  with  lardaceous 
disease.     (See  p.   227.) 

Fatty  degeneration  of  the  blood-vessels  is  a  disease  of   the  capillaries. 


VASCULAR   SYSTKM. 


531 


the  small  arteries,  and,  rarely,  the  veins.  It  occurs  most  commonly  in 
the  capillaries  of  the  brain.  As  to  cause,  it  is  observed  in  connection 
with  (i)  old  age,  (2)  pernicious  anemia,  (3)  phosphorus-poisoning, 
and  (4)  ijjencral  dehilitatinj^^  conditions.  The  chan^'c  in  the  intima 
resembles  the  de!j:encrative  lesion  of  atheroma,  but  is  not  accompanied 
by  any  fibrous  tissue  formation  or  other  i)henomena  so  constantly 
associated  with  atheroma.  The  vessel-walls  are  converted  into  a  fatty 
cellular  debris  without  any  preceding  inflammatory  i)rocess  like  that  of 
atheroma. 

An  axieurysm  is  a  tumor-like  sac,  containing  blood  and  communi- 
cating with  an  artery.     (See  Fig.  232,  p.  464.) 

The  sac  may  be  composed  of  one  or  more  coats  of  the  blood-vessel, 
when  it  is  known  as  a  true  aneurysm  or  arterial  ectasia;  when  the  limiting 
membrane  of  the  cavity  is  formed  by  the  condensed  tissues  around  the 
vessel,  the  wall  of  which  has  entirely  given  way,  the  condition  is  spoken 
of  as  a  false  aneurysm. 

Causes  of  AnenrysDi. — Aneurysms  are  said  to  be  (i)  traumatic  or 
(2)  idiopathic.  As  nothing  occurs  without  a  cause,  it  would  be  better 
to  call  the  latter  cryptogenic.  Further,  the  causes  of  aneurysm  are  said 
to  be  (i)  predisposing  and  (2)  exciting.  Of  the  former,  many  of  the 
degenerations  of  the  vessel-walls  that  have  been  studied,  and  that  weaken 
the  artery,  are  eminently  predisposing;  atheroma  is  doublv  dangerous 
in  that  it  renders  the  vessel  rigid  and  at  the  same  time  weakens  the  wall. 
The  fact  that  syphilis  favors  or  often  brings  about  arterial  disease  or 
degeneration  makes  it  a  predisposing,  if  not  truly  an  exciting,  cause  of 
aneurysm.  Between  the  thirtieth  and  fortieth  years  of  life  the  degener- 
ative arterial  changes  described  in  the  preceding  pages  are  likelv  first  to 
evince  themselves;  the  heart  is  yet  in  full  power,  in  most  individuals, 
and,  with  the  maintained  cardiac  force  and  dirriinished  strength  of  the 
diseased  arterial  wall,  rupture  or  dilatation  of  the  blood-vessel  is  likely 
to  ensue.  Suddenly  developed,  jjowerful  cardiac  force — such  as  mav 
occur  from  a  hard  lift,  sudden  s])ring,  or  vault — doubles  the  demand 
on  the  semi-rigid  and  weakened  vessel-walls,  and  may  induce  rupture 
of  one  or  more  of  the  arterial  coats.  The  male  is  more  liable  to  these 
sudden  exertions,  and  hence  aneurysm  is  much  more  prevalent  in  that 
sex.  Injury  to  the  blood-vessel  may  be  an  exciting  cause  or  a  predis- 
posing element;  if  the  injury  be  a  puncture,  it  may  be  followed  imme- 
diately by  a  false  aneurysm;  a  contusion  may  give  rise  to  arterial 
changes  that  weaken  the  wall  and  cause  it  to  yield  when  subjected 
to  a  strain  that  would  not  influence  the  normal  vessel.  Stretching  and 
twisting  of  vessels,  as  in  dislocations  and  fractures,  or  in  their  reduction, 
have  been  followed  immediately  by  aneurysmal  dilatation.  Histologic 
studies  of  aneurysmal  vessels  in  man,  and  examination  of  arteries  in 
which  experimental  aneurysms  have  been  produced,  constantly  disclose 
alterations  in  the  elastica.  The  changes  may  be  structural  and  mani- 
fested by  fragmentation  or  larger  breaks  in  the  elastic  strata;  it  is 
possible  that  breaks  in  the  elastica  are  preceded  by  chemic  alteration, 
and  that  the  latter  may,  without  structural  change,  ijemiit  dilatation. 
Schwyzer  affimis  that  alterations  in  the  collagenous  tissues  of  the  arterial 
wall  are  im{)ortant  factors  in  the  production  of  aneurysm.  It  is  prob- 
able that  in  the  aneurysms  due  to  acute  infective  lesions  of  the  vessels 
both  elastic  and  fibrous  tissues  are  involved. 


532 


SPECIAL  PATHOLOGY. 


Form  of  AnciirysDi. — (A)  Classified  by  the  shape:  (i)  Cylindrie, 
uniform  distention  of  the  vessel.  (2)  Fusiform,  or  spindle-shaped. 
(3)  A  cirsoid  aneurysm  consists  of  a  number  of  arteries  irregularly 
dilated  and  lengthened  throughout  a  considerable  part  of  their  courses. 
When  a  single  artery  is  involved,  the  term  aneurysmal  varix  has  been 
applied;  the  same  name  is  also  used  for  arterio-venous  aneurysm  and 
should  be  suppressed.     Arterial  varix  is  better.     (4)  Saccular,  in  which 


Fig.  266. — Symmetric  .Aneurysm  of  the  Abdominal  .\orta. — {Specimen  in  Ihe  museum  oj  the  Jefjerson  Medical 

College.) 

A.  Sacrum.  B.  Fourth  lumbar  vertebra;  the  anterior  part  of  the  body  has  been  eroded  by  the  aneurysm.  \t 
the  inferior  margin  calcareous  material  has  been  thrown  out  anteriorly;  this  covers  the  cartilage.  C.  Body  of 
third  lumbar  vertebra.  .\t  D  the  aneurysmal  sac  has  been  cut  away  to  show  the  absorption  of  the  body  of 
the  vertebra.  E.  Ca\ity  of  the  aneiurysm.  .\t  the  lower  part  of  the  ca\-ity,  between  the  points  of  exit  of  the 
two  iliac  arteries,  a  sharp  spicule  of  a  calcareous  plaque  will  be  seen  projecting  upward.  F.  Left  iliac  artery; 
the  right  iliac  artery  -n-ill  be  seen  as  a  short  stump  at  the  lower  part  of  the  aneurysmal  wall. 


a  distinct  pouch  is  formed.  If  on  one  side  of  the  vessel  and  commun- 
icating by  a  small  opening,  it  is  spoken  of  as  asymmetric;  if  the  sac 
be  uniformly  distributed  around  the  vessel,  as  in  the  miliary  aneur3'-sm 
of  the  brain,  it  is  symmetric.  (5)  Arteriovenous  aneurysm  results  from 
any  injury  which  establishes  a  communication  between  an  arter}'  and 
a  vein.  When  the  wall  sharply  defines  the  aneurysm,  it  is  spoken  of 
as  circumscribed;   when  the  blood  cavitv  terminates  in  infiltrated  tissue, 


VASCUI.AR   SVSTIv.M.  533 

the  Lcnn  diffuse  is  applied;  the  hitter  is  necessarily  a  false  aneurysm. 
When  small  and  multiple,  ])articularly  in  the  brain,  they  are  called 
viiliary  a)ii'urYsnis. 

(H)  Classified  by  the  cause:  (i)  J  rauiiui tic  aneurysm.  An  aneurysm 
arising  suddenly,  as  from  an  ulcerative  endarteritis  or  trauma,  is  some- 
times spoken  of  as  an  acute  aiieurys)ii;  (2)  idiopathic  or  cryptogenic; 
(3)  eutholic,  due  to  proximal  distention  in  occluded  vessels,  usually  ter- 
minal; (4)  dissecting  aneurysm  due  to  blood  dissecting  between  the 
layers  or  coats  of  a  vessel's  wall ;  (5)  verminous  aneurysm,  one  containing 
a  parasite  such  as  is  found  in  the  mesentery  of  the  horse. 

(C)  Classification  based  on  duration  atid  changes  in  the  ivall:  (i)  An 
acute  aneurystn  or  recent  aneurysm  is  one  quickly  developed,  and  is 
usually  traumatic;  (2)  chronic  or  old  aneurysm,  an  aneurysm  that  has 
persisted  longer,  as  shown  by  the  changes  that  its  walls  have  undergone. 

Results  of  Aneurysm. — (i)  Disturbance  of  blood  distribution;  (2) 
pressure  on  surrounding  tissues  and  organs;  (3)  rupture;  (4)  cure  and 
arrest  of  further  circulation  through  the  altered  vessel. 

Cure  of  Aiu^urysni. — The  first  step  in  the  spontaneous  obliteration 
of  an  aneurysm  is  the  formation  of  a  clot  or  fibrinous  deposit  in  the 
cavity;  this  may  be  in  layers  (laminated)  (see  Fig.  232,  p.  464),  or 
it  may  be  a  central  clot  apparently  formed  as  one  mass.  By  occluding 
the  point  of  exit  the  circulation  is  arrested.  The  coagulum  may  remain 
practically  unaltered  for  years.  The  writer  saw  a  case  in  wdiich  all 
sym])toms  except  the  presence  of  the  tumor  had  been  absent  for  eight 
years,  the  proximal  and  distal  ends  of  the  vessel  having  undergone 
obliterative  arteritis.  In  time,  blood-vessels  may  permeate  the  clot 
and  organization  of  the  mass  may  ensue.  Occasionally  some  of  the 
young  blood-vessels  dilate  and  are  converted  into  channels  transmitting 
blood  from  the  proximal  to  the  distal  parts  of  the  vessel,  and  thereby 
re-establishing  the  circulation.  (See  Canalization  of  a  Thrombus,  Fig. 
148,  p.  276.)  Organization  of  a  clot  formed  within  an  aneurysm  ter- 
minates in  the  production  of  a  mass  of  fibrous  tissue,  which  contracts, 
and  often  perpetuates  the  contour  of  the  cured  aneurysm.  Above  and 
below  the  healed  sac,  the  artery  involved  is  occluded  bv  obliterative 
changes  extending  to  the  first  branch  through  which  the  blood  con- 
tinues to  How. 

Hypertrophy  of  Arteries. — When  a  large  arterial  trunk  is  obstructed, 
the  blood-suj)j)ly  to  the  part  beyond  may  be  maintained  by  enlargement 
of  branches,  rising  above  the  ])oint  of  obstruction,  and  anastomosing 
with  branches  from  below;  the  latter  may  also  increase  in  size.  The 
condition  is  one  apparently  of  true  hypertrophy.  The  anastomotic 
circulation  eventually  becomes  as  comj)etent  to  carry  on  the  functions 
of  nutrition  as  were  the  normal  vessels.  When  this  occurs,  it  is  said 
that  a  collateral  circulation  has  been  established  bv  anastomosis. 


VEINS. 

Normal  Structure. — Normal  veins  possess  essentially  the  same  struc- 
ture as  arteries,  e.xcept  that  the  tunica  media  is  very  much  less  developed, 
and  hence  the  walls  are  thinner.  Many  of  the  veins  are  supplied  with 
valves,  and  thus  diflfer  from  the  arteries. 


534  SPECIAL  PATHOLOGY. 

Bennett^  and  others  have  described  congenital  sacculations  and 
cystic  dilatation  of  the  veins  occurring  independently  of,  or  associated 
with,  varicosity.  Such  abnormalities  may  involve  a  part  or  all  of  the 
wall  and  hence  may  be  symmetric  or  asymmetric.  The  veins  of  the 
neck  and  inguinal  regions,  and  the  saphena  veins,  may  be  affected;  the 
condition  is  sometimes  called  congenital  varix. 

Phlebitis,-  Inflammation  of  Veins. — Inflammatory  processes  analo- 
gous to  those  already  described  as  occurring  in  the  arteries  (see  p.  520) 
take  place  in  the  veins,  the  most  important  of  which  are  the  infective 
forms — infectious  phlebitis.  As  the  current  in  the  veins  is  from  the 
smaller  lumen  to  a  larger  one,  dislodgment  occurs,  and  emboli  are  thrown 
off  in  large  numbers.  When  considering  thrombosis  and  embolism,  this 
point  was  mentioned.  (See  p.  275.)  The  source  of  the  infection  in 
veins  may  be  by  (i)  direct  infection,  as  in  wounds;  (2)  mural  implanta- 
tion; (3)  continuity  of  spread  (that  is,  passing  directly  along  the  vessel- 
wall)  ;  (4)  by  contiguity,  from  periphlebitis.  As  examples  of  the  last  two 
may  be  cited  the  spread  from  infected  uterine  sinuses  to  pelvic  veins, 
and  the  extension  of  suppurative  mastoid  disease  to  the  adjacent  intra- 
cranial sinuses,  respectively.  Pyemia  and  other  forms  of  bacteremia 
are  frequently  due  to  phlebitis;  the  latter  may  be  secondary  to  the 
blood  infection. 

When  the  inflammation  begins  in  the  intima,  as  a  result  of  exten- 
sion along  the  wall,  a  thrombus  usually  attends  the  progress  of  the 
inflammation,  justifying  the  term  thrombophlebitis.  The  presence  of 
bacteria  in  practically  all  these  thrombi  is  usually  admitted ;  in  many 
of  them  pyogenic  organisms  are  almost  exclusively  the  cause,  and  such 
venous  inflammation  has  received  the  name  suppurative  phlebitis. 
In  other  cases  neither  suppuration,  softening,  disintegration,  fragmen- 
tation, nor  dislodgment  occurs.  The  absence  of  such  changes  indicates 
that  the  condition  is  not  suppurative,  but  by  no  means  excludes  infection, 
such  as  typhoid  fever,  influenza,  and,  as  shown  more  recently,  rheuma- 
tism. The  simple,  bland,  or  noninf active  phlebitis,  such  as  follows 
injury  of  the  vein  without  infection,  is  inconsequential,  and  is  usually 
unattended  by  secondary  processes.  In  some  cases  the  patient  may 
suffer  repeated  attacks,  constituting  what  is  called  recurrent  phlebitis. 

The  results  of  phlebitis  are  influenced  by  the  character  of  the  accom- 
panying infection,  and  especially  by  the  changes  occurring  in  the  result- 
ing thrombus.  The  latter  I  have  considered  when  dealing  with  throm- 
bosis (p.  275).  When  the  inflammation  is  attended  by  the  formation 
of  an  occluding  thrombus,  the  affected  vein  is  frequently  obliterated. 
Osier ^  has  been  able  to  collect  twenty-nine  instances  of  thrombosis 
involving  the  superior  vena  cava;  to  these  should  be  added  the  instance 

1  "Lancet,"  April  12,   1889,  p.  788. 

'See  references  to  Thrombus,  p.  270.  Also  Censier,  "Revue  de  Med.,"  vol. 
xxii.  Pinatelle,  "Gaz.  Hebdom.  de  Med.,"  Dec.  19,  1901.  Oettinger,  "La  Se- 
maine  Med.,"  Feb.  12,  1902.  Terriberr}-,  "Med.  News."  April  12.  1902.  Hess, 
"Deut.  med.  Woch.,"  June  26,1902.  XXVIII  Jahrg.  Ducastel,  These  de  Paris, 
1903.  Chantemesse,  "Acad.  deMed.,"  July  28,  1903.  Aldrich.  "N.  Y.  Med. 
Jour.,"  March  5,  1904,  p.  442.  Heller,  "Berl.  klin.  Woch.,"  June  9,  1904,  No.  23. 
Galtier  and  Pierre.  "Gaz.  des  Hop.  Civil,  et  Mil.,"  Sept.  3,  1904.  Ledderhose, 
"Deut.  med.  Woch.,"  Oct.  20,  1904.  Cobbledick,  "Practitioner,"  Nov.,  1904, 
p.  707.  Forster,  "Wien.  klin.  Woch.,"  Nov.  3,  1904,  p.  1175.  Halbron,  "La 
Presse  Med.,"  March  18,   1905,  p.   173.      LetuUe,  "Soc.  de  Biol.,"  April  8,  1905. 

^"Bull.  of  Johns  Hopkins  Hospital,"  July,  1903. 


VASCULAR  SYSTKM, 


5.S5 


reported  by  Cobbledick.  The  circulation  in  the  area  drained  by  the 
occluded  vessel  is  more  or  less  ini])eded,  the  nutrition  of  the  structures 
disturbed,  and  edema  is  frequently  present. 

Tuberculosis  of  the  veins  is  manifested  by  changes  essentially  similar 
to  those  already  described  (see  p.  529)  as  occurrinjj  in  the  arteries,  but 
is  much  more  frequent.  The  paths  of  infection  in  the  two  kinds  of 
vessels  are  essentially  similar,  and  the  dangers  from  dissemination  of 
the  bacilli  by  the  blood  are  practically  identical.' 

Syphihs  of  the  veins  may  be  of  the  sclerotic  or  gummatous  type. 
Xodular  svphilitic  ]>hlcbitis  gives  rise  to  circumscribed  enlargement 
(gummata)  along  the  course  of  the  affected  vein.  In  other  cases  the  in- 
duration is  cord-like  and  not  nodular. 

Chronic  phlebitis  or  phlebosclerosis  is  a  morbid  entity  studied  by 
Thoma,  who  believes  it  to  be  part  of  general  vascular  disease  {angio- 
sderosis).  The  wall  of  the  vein,  usually  immediately  beneath  the  in- 
tima,  shows  a  marked  increase  in  the  fibrous  tissue,  which  may  undergo 
hvaline  degeneration ;  the  elastica  is  commonly  aflfected 
as  in  arteriosclerosis  and  thrombosis  is  not  infrequently 
present. 

Varicose  Veins,  or  Phlebectasia-  (Synonyms.  Varix, 
Varicosity). — This  condition  consists  of  more  or  less 
irregular  dilatation  of  the  veins :  as  a  rule,  associated  with 
alterations  in  their  walls  and  nutritive  changes  in  the  area 
involved. 

Sites. — Veins  of  the  leg  and  thigh;  plexus  pampini- 
formis;  hemorrhoidal  veins;  occasionally,  the  veins  of 
the  abdominal  wall,  and.  rarely,  intra-abdominal  veins — 
peri -uterine,  renal,  or  mesenteric. 

Causes. — Dilated  veins  may  result  from  (i)  obstruc- 
tion to  the  onward  flow  of  the  blood:  e.  g.,  tumors  of 
the  pelvis,  pregnancy,  etc.,  inducing  varicosity  of  the 
veins  of  the  leg  and  of  the  rectum;  cirrhosis  of  the 
liver,  obstructing  the  veins  returning  from  the  alimentary 
canal;  tight  garters  or  other  constricting  bands  are  also 
causes.  (2)  Diseases  of  the  central  organ  of  circulation, 
leading  to  venous  stasis.  (,s)  Pulmonary  obstruction, 
inducing  stagnation  of  the  blood  in  the  veins.  (4)  Inflammation  of 
the  veins,  (a)  leading  to  softening  of  the  walls,  and  thus  favoring  ex- 
pansion, and  (b)  obliteration  or  narrowing  of  a  large  vein,  such  as  the 
femoral,  bv  a  thrombus  or  by  contraction,  thereby  increasing  the 
intravenous  pressure  in  the  vessel,  distal  to  the  point  of  obstruction. 
Bennett  believes  there  is  always  a  congenital  defect,  in  the  presence  of 
which  other  conditions  may  produce  varicosity;  he  also  regards  many 
cases  as  congenital. 

Forms. — (i)  When  the  dilatation  is  regular,  symmetric,  and  not 
associated  with  lengthening,  the  condition  is  known  as  simple  dilatation; 
(2)  when  the  vein  is  dilated  and  tortuous,  owing  to  apparent  lengthening 
as  well  as  to  dilatation,  it  is  sx)oken  of  as  cir<oiii  dilatation:   {i,\  when 


Fig.  267. — Varicose 
Veins  or  the 
Leg.— (ComW.) 


'  See  Tuberctilosis,  p.  154 

'Thorel,  "  Lubarsch  and  Ostertag  s  tr^(.i'ni>'-<,'  .1  .iip^cm.  I'.un.  \i.  j'.itn  .vna 
Neunter  Jahr.  I.  Abt..  1003,  p.  113.  Leddcrhosf.  "Deut.  med.  Woch.."  Oct. 
1904.      Bennett.  "Lancet       V"-    22,  1902,  p.   1374 


20, 


536  SPECIAL  PATHOLOGY. 

the  distention  is  irregular,  saccular,  or  upon  alternate  sides,  the  con- 
dition is  called  varicose  dilatation.  (4)  An  ampiiUary  dilatation  of  the 
veins  has  also  been  described;  this  form  occurs  particularly  near  the 
femoral  ring  and  has  been  mistaken  for  hernia.  By  some  writers  the 
congenital  sacculations  and  cystic  dilatations,  referred  to  on  page  534, 
are  placed  in  this  group. 

Results  of  Phlebectasia. — The  slowed  circulation  and  passive  congestion 
lessen  the  nutrition  of  the  tissues  in  the  area  drained  by  the  involved 
vessels;  as  a  result  of  failure  to  remove  effete  materials,  degenerative 
or  even  necrotic  processes  may  ensue.  Edema  may  occur;  clots  may 
form  in  the  veins ;  the  stretching  of  the  walls  usually  renders  the  valves 
inefficient;  as  a  result  of  the  lowered  vitality,  slight  bruises  or  super- 
ficial excoriations  are  followed  by  infection  in  the  diseased  area,  and 
extensive  ulceration  commonly  ensues.  In  the  testicle  lessened  nutri- 
tion undoubtedly  results,  and  in  some  instances  this  may  be  followed 
by  atrophy  of  the  organ.  In  the  rectum,  clotting  may  occur  in  the 
dilated  hemorrhoidal  veins,  and  violent  inflammatory  processes  may 
follow,  or  the  venous  mass  may  ulcerate  and  bleed,  or  may,  by  its  size, 
cause  more  or  less  obstruction  to  the  passage  of  fecal  matter. 

Tumors  of  Blood-vessels. — Primary  tumors  of  the  blood-vessels  are 
rare.  They  must  be  of  the  connective-tissue  series.  Sarcomata  invade 
the  vessels  rapidly,  and  particularly  the  veins,  by  which  they  not  un- 
commonly spread.  Cancers  can  implicate  the  vessels  only  as  secondary 
growths  or  by  direct  extension  of  the  neoplasm  into  the  vessel- 
wall.  (For  tumors  of  the  blood-vessels,  blood-vessel  tumors,  see  Heman- 
giomata,  p.  345.) 

LYMPH-VESSELS. 

Nutrition  of  the  tissues  is  largely  maintained  by  the  lymph,  which 
is  derived  from  the  blood,  and  circulates  in  the  interstices  or  primitive 
lymph-spaces.  (See  Edema,  p.  267.)  It  is  generally  believed  that, 
primarily,  the  lymph  is  free  in  the  reticulum  between  the  cells,  the 
cavities  within  which  it  is  lodged  being  called  the  primitive  lymph- 
spaces.  From  these  structures  there  arise  the  lymph  capillaries, 
which  join  to  form  the  lymphatic  vessels.  The  larger  lymph-vessels 
possess  walls  structurally  resembling  the  walls  of  blood-vessels.  The 
lymphatic  capillaries,  or  lymph  canaliculi,  are  structurally  like  the 
blood  capillaries,  except  that  they  show  great  irregularity  in  diameter, 
often  exhibiting  saccular,  cylindric.  and  fusiform  dilatations. 

Malformations  of  the  lymph-vessels  are  usually  manifested  as  con- 
genital tumors  {lymphangiomata),  which  have  been  considered  elsewhere. 
(See  p.  346.)  As  in  the  blood-vessels  anomalies  of  origin  and  course 
are  occasionallv  observed,  so  in  the  lymphatic  vessels  evidences  of 
abnormal  distribution  of  the  channels  are  sometimes  exhibited.  Thus, 
carcinoma  of  the  mamma,  which  usually  first  invades  the  axillary 
nodes,  may  show  initial  glandular  involvement  in  the  supraclavicular 
nodes,  thereby  proving  that,  in  some  instances,  at  least,  the  lymph 
stream  from  the  breast  passes  in  a  direction  at  variance  with  the  normal. 

Obstruction  of  a  lymph-vessel  may  result  from  pressure,  as  when 
adjacent  tumors,  aneurysms,  and  cicatrices  collapse  its  walls;  injury, 
inflammation,  thrombosis,  tuberculosis,  and  animal  parasites  (such,  for 


VASCULAR  SYSTEM.  537 

example,  as  the  filaria,  see  p.  207)  may  also  occlude  its  lumen,  or  ex- 
cision of  lymph-nodes,  extensive  suppurative  processes,  and  lymphan- 
i^eiolitis  may  destroy  the  ducts  traversing  an  area.  Cancer  spreading 
by  the  lymphatics  may  plug  the  vessels.  The  changes  resulting  from 
occlusion  of  a  lymph-vessel  depend  largely  upon  the  importance  of  the 
vessel  and  upon  the  possibility  of  collateral  anastomoses.  The  distribu- 
tion of  the  lymphatic  system  commonly  affords  al)unilant  oi)portunity 
for  the  lymph  to  jjass  through  some  circuitous  route  when  obstructed 
in  its  nomial  course.  When  passage  in  this  way  can  not  be  provided, 
the  resulting  obstruction  is  associated  with  edema  in  the  area  involved. 
(See  Edema,  p.  207.)  In  other  cases,  either  with  or  without  edema, 
the  lymphatic  vessels  distal  to  the  obstruction  dilate.  The  dilatation 
may  be  restricted  to  a  small  area,  in  which  case  a  lymphangioma  results, 
or  it  may  be  diffuse,  and  manifested  by  the  occurrence  of  small  cysts 
in  the  tissue  involved.  In  still  other  instances,  either  with  or  without 
any  of  the  foregoing  conditions,  more  or  less  edema,  with  marked  ]>v(j- 
liferation  of  the  connective  tissues,  occurs,  giving  rise  to  elephantiasis 
(see  J).  209)  and  elephantoid  conditions  (see  p.  210).  Manson's  statistics 
show  that  in  96.84  {)er  cent,  of  the  cases  of  elephantiasis  the  lower 
extremities  are  involved;  in  5.S6  per  cent,  the  upper  extremities;  and 
in  2.3  per  cent,  the  scrotum  manifests  the  change.  The  enormous  over- 
growth of  the  connective  tissues  may  be  appreciated  by  the  fact  that 
the  scrotum  sometimes  attains  a  weight  of  200  pounds.  On  incision, 
the  tissue  involved  is  found  to  consist  largely  of  white  fibrous  elements 
superficially,  and  deeper,  of  a  "blubbery-looking  dropsical  tissue." 
The  lymphatic  nodes  of  the  area  involved  are  commonly  enlarged  and 
fibrous. 

Occlusion  of  the  thoracic  duct  affords  a  slightly  different  picture 
by  reason  of  the  fact  that  the  vessel  transmits  chyle.  It  may  be 
obstructed  from  the  same  causes  as  those  already  given  for  lym- 
phatic trunks  elsewhere.  Thrombosis  involving  the  left  innominate 
vein  occludes  the  duct  at  the  point  where  it  empties  its  contents  into 
the  venous  circulation.  As  in  obstruction  of  other  lymph-channels,  it 
is  possible  to  have  occlusion  of  the  thoracic  duct  without  any  untoward 
manifestation,  in  which  case  the  fluid  that  it  normally  transmits  must 
enter  the  circulation  through  some  circuitous  route.  As  a  result  of 
obstruction,  chylous  ascites  may  occur.  (See  p.  454.)  Similar  effusions 
are  occasionally  observed  in  the  pleural  cavities,  and  chylocele — an 
accumulation  in  the  tunica  vaginalis  testis — at  times  follows  obstruction 
to  the  course  of  the  intra-abdominal  lymph.  In  other  cases  there  is  an 
accumulation  of  chyle  in  the  lymphatics  of  the  scrotum,  constituting 
so-called  lymph-scrotum  ;  and  in  still  other  instances  the  obstruction 
to  the  onward  fi<:)w  of  the  lymph  is  manifested  by  the  occurrence  of 
chyluria. 

As  a  result  of  obstruction  to  the  fiow  of  the  chyle  along  its  normal 
course  in  the  vessels  of  the  mesentery,  cysts  are  occasionally  forme<l. 
Not  infrequently  chyle-cysts'  closely  resemble  abscesses,  for  which  they 
have  been  mistaken.  A  microscopic  or  chemic  examination  of  their 
contents  prevents  this  error  in  diagnosis.  Obstruction  to  the  onward 
flow  of  chyle  materially  interferes  with  nutrition,  leading  t<i  nii.r<-  or 
less  anemia,  and  eventually,  in  many  cases,  to  emaciation. 

'See  reference,  p.  4S0.     Also  Meriel.  "  Revue  de  Chir.. "  Dec.  10.  kidi.  y    730. 


538  SPECIAL  PATHOLOGY. 

Lymphangitis,  angioleucitis,  or  inflammation  of  the  lymphatic  vessels 
occurs  in  two  forms — acute  and  chronic. 

The  acute  form  is  usually  due  to  infection  by  pyogenic  organisms, 
and  is,  therefore,  commonly  suppurative  in  character.  It  may  ac- 
companv  erysipelas  or  may  result  from  the  extension  of  infections, 
such  as  abscesses.  The  dissection  and  postmortem  wounds,  of  common 
occurrence  and  great  mortality  before  the  proper  injection  of  anatomic 
material,  were  typical  exam'ples  of  acute  suppurative  lymphangitis. 
That  acute  inflammation  of  the  lymphatic  vessels  is  not  always  the 
result  of  infection  is  indicated  by  the  occurrence  of  a  typical  form  due  to 
fllaria,  and  of  another  variety,'  brought  about  by  the  introduction  of 
venom  into  the  lymph-spaces.  Severe  bruises  and  burns,  the  former 
often  without  any  solution  in  the  continuity  of  the  skin,  may  be  followed 
bv  acute  Ivmphangitis. 

The  morbid  anatomy  of  the  condition  depends  largely  upon  whether 
the  process  is  restricted  to  the  lymph-spaces  or  passes  be3'ond  these 
structures  and  invades  the  vessel  properly  so  called.  In  the  former 
instances  (acute  reticular  lymphangitis)  there  is  dilatation  of  the  blood- 
vessels, giving  rise  to  redness,  which  often  shows  a  peculiar  motthng 
due  to  its  irregular  distribution.  More  or  less  edema  (swelling)  is 
present.  In  the  acute  tubular  lymphangitis  the  lines  of  hyperemia  and 
swelling  follow  the  course  of  the  lymphatic  vessels;  usually  they  are 
broader  than  the  duct,  as  a  result  of  the  presence  of  an  associated  perilym- 
phangitis, or,  rather,  a  reticular  lymphangitis  surrounding  the  inflamed 
vessel.  On  microscopic  examination,  the  lymph-spaces  will  be  found  to 
contain  numerous  leukocytes,  and  later, in  pyogenic  infection,  the  accumu- 
lation may  be  sufficient  to  justify  its  being  caUed  a  distinct  pus  collection. 
Fibrin  is  nearlv  always  present  at  some  stage  in  the  process.  In  the 
lymphatic  vessels  swelling  and  desquamation  of  the  endothelium  occur, 
associated  with  more  or  less  marked  leukocytic  migration,  and  not  in- 
frequently with  thrombosis.  The  extent  and  termination  depend  largely 
upon  the  character  of  the  infection  and  upon  the  resistance  of  the 
individual.  In  areas  of  tymphatic  obstruction — such  as  lymph-scrotum 
and  elephantiasis — the  absence  of  sufficient  protective  powers  on  the 
part  of  the  tissues  may  lead  to  disastrous  infections.  In  other  cases 
the  virulence  of  the  infecting  agent  may  be  overwhelming,  and  asso- 
ciated with  the  production  of  poisons  that  rapidly  destroy  life,  or  by 
the  diffusion  of  bacteria  into  the  lymphatic  nodes,  and  eventually  into 
the  blood-vessels,  septicemia  or  pyemia  may  ensue.  In  still  other  in- 
stances the  virulence  of  the  infection  may  be  slight  or  the  resistance  of 
the  tissues  marked,  and  in  either  case  the  process  quickly  subsides. 

Chronic  lymphangitis  may  follow  the  acute  form  or  may  result  from 
graduallv  developing  obstruction  to  the  onward  flow  of  lymph.  It  is 
frequently  observed  in  lymphangiomata.  It  is  manifested  by  more  or 
less  dense  edema  of  the  area  involved,  with  proliferation  of  the  connec- 
tive tissue,  leading  to  a  true  fibrous  induration. 

Lvmphangiectasis  and  lymphangioma  have  been  referred  to  in  con- 
sidering tumors.  (See  p.  346.)  Tumors  of  the  lymph-vessels,  aside 
from  those  resulting  from  lymphangiectasis,  either  congenital  or  ac- 
quired, are  usually  secondary,  and  are  due  to  invasion  of  the  adjacent 
tissues  or  primitive  lymph-spaces.  Endothcliomaia  of  the  serous  mem- 
branes are  usually  regarded  as  primary  tumors  arising  from  the  endo- 


VASIL'I.AU   SYSTKM.  5  ,V; 

theliutii,  ami  arc  allied  to,  if  not  identic-al  willi,  similar  tumors  tin.- 
origin  of  which  is  the  cmiothelium  of  smaller  lymph-spaces  or  lymph- 
ducts.  The  extension  of  cancer  by  the  lymph-spaces  has  already  been 
considered.     (See  p.  32,;.) 

In  connection  with  or  indepentlcnt  of  associated  tuberculosis  of  the 
lvm[di-nodes  the  process  may  involve  the  vessels.  Extension  onward  to 
the  nearest  nodes  or  to  the  blood -stream  is  possible.  When  tubercu- 
losis occurs  in  the  thoracic  duct' — either  as  a  result  of  mural  implantation 
of  tubercle  bacilli,  which  have  found  entrance  near  the  periphery  of 
its  distribution,  or  when  an  adjacent  tuberculosis  invades  the  structure 
— disaster  due  to  systemic  dissemination  is  prone  to  follow. 
'See  Longcope;    reference  given  on  p.   154. 


CHAPTER  VII. 
MUCOUS    MEMBRANES. 

Normal  Structure. — A  mucous  membrane  consists  essentially  of 
three  parts:  (i)  Upon  the  surface,  a  layer  of  epithehal  cells;  (2)  a  base- 
ment membrane,  upon  which  these  cells  rest;  (3)  the  submucous  con- 
nective tissue,  in  which  ramify  the  blood-vessels,  lymphatics,  and  nerves 
essential  to  the  life  and  function  of  the  layers  above. 

I .  The  epithelial  layer  varies  in  two  particulars :  (a)  in  the  character 
of  the  epithelium  and  (6)  in  the  number  of  layers.  When  the  function 
of  the  epithelium  is  largely  protective,  stratification  is  the  rule;  when 
secretion  is  the  essential  function,  there  is  commonly  but  one  layer: 
e.  g.,  on  the  tongue  numerous  layers  are  found,  while  in  the  tubules  of 
the  stomach,  the  acini  of  glands,  and  the  secreting  structures  of  the 
kidney,  etc.,  but  a  single  stratum  exists.  When,  in  addition  to  protec- 
tion, propulsive  force  is  needed,  or  when  the  latter  alone  is  demanded, 
the  epithelial  cells  are  supplied  with  cilia,  as  in  the  bronchi  and  Fallopian 
tubes.  In  all  mucous  membranes  possessing  stratified  epithelium  there  lies 
immediately  adjacent  to  the  basement  membrane  a  genetic  layer  analo- 
gous to  the"  cylindric-cell  layer  of  the  rete  mucosum  of  the  skin.  When 
the  epithelial  covering  is  simple  (nonstratified),  as  in  the  pulmonary 
vesicles  and  renal  tubules,  a  distinct  genetic  layer  may  not  be  demon- 
strable. Mucous  membranes  so  constructed  must,  after  exfoHation  or 
destruction  of  a  single  layer,  recoat  the  connective-tissue  basement 
membrane  from  the  viable  cells  at  the  margin  of  the  area  involved, 
exactly  as  the  epithelial  regeneration  progresses  over  the  surface  of  an 
ulcer  undergoing  repair. 

Epithelial  cells  possess  the  remarkable  faculty  of  manufacturing 
from  supplied  nutrition  new  chemic  compounds  not  existing,  as  such, 
in  the  pabulum  supplied:  e.  g.,  the  secretions  of  the  salivary  glands 
the  gastric  follicles,  the  pancreas,  the  kidney,  etc.  Every  mucous  sur- 
face is,  therefore,  a  laboratory,  and  this  peculiarity  has  given  the  mem- 
brane the  name  specialized,  indicating  that  it  possesses  characters  emi- 
nently its  own.  While  all  mucous  membranes  elaborate  something, 
the  rnost  constant  element  is  mucus;  when  a  mucosa  is  altered  by  dis- 
ease, mucus  not  uncommonly  forms  a  conspicuous  product  in  the  altered 
secretion;  as  a  rule,  the  greater  the  functional  perversion,  the  more 
abundant  the  abnormal  products,  and  the  larger  the  quantity  of  mucus. 
As  the  function  of  the  epithelial  cell  is  dependent  largely  upon  the  pabu- 
lum supplied,  and  as  this  supply  is  controlled  by  the  subepithelial  layers, 
it  becomes  evident  that  the  alteration  of  the  basement  membrane,  or 
of  the  submucosa,  must  affect  the  activity  of  the  superimposed  epithe- 
lium. 

2.  The  Basement  Membrane  {Mcmhrana  propria).— This  structure 
is  mesoblastic  in  origin,  composed  of  fibrous  tissue  and,  in  some  situa- 
tions, a  scant  supply  of  unstriped  muscle-cells,  and  a  varying  quantity  of 

540 


Mucors  mi;mhk.vni;s.  541 

elastica.  The  thickness  of  the  basement  membrane  varies  j,'reatly; 
thus,  in  the  mouth  and  nose  it  is  of  a  discernible  thickness,  while  in  the 
wall  of  the  pulmonary  alveoli  it  is  demonstrated  with  dilliculty.  When 
great  changes  in  the  volume  and  surface  of  the  organ  are  likely  to  occur, 
the  basement  membrane  may  be  thrown  up  in  irregular  ridges;  in  this 
wav  the  gastric  mucosa  is  enabled  to  adapt  itself  to  the  changes  in  vol- 
ume constantly  manifested  by  the  stomach.  By  some  it  is  claimed  that 
nerves  and  lymphatics  penetrate  the  membrana  jjrojjria  and  present 
themselves  immediately  in  the  epithelial  layer.  It  is  not.  however, 
probable  that  such  is  the  case;  as  in  all  mucosa;  the  basement  membrane 
is  the  line  between  the  connective  and  epithelial  tissues,  it  seems 
reasonable  to  assume  that  it  is  merely  pushed  as  a  thin  layer  ahead  of 
the  nerve-fibers,  and  that  the  lymphatics  open  by  stomata  immediately 
beneath  or  into  the  genetic  layer  of  epithelium  when  such  a  structure 
exists. 

3.  The  snlvtnicosa,  or  submucous  connective-tissue  layer,  is  of  the 
greatest  importance,  and  varies  more  than  either  of  the  preceding.  In 
a  part  of  the  nasal  fossae  it  is  erectile;  where  an  organ  is  subject  to  great 
alteration  in  surface,  like  the  stomach,  it  is  especially  abundant;  where 
it  is  not  called  upon  for  such  rapid  alterations  in  surface  during  brief 
intervals,  it  may  be  wanting,  as  in  the  uterus,  where  it  is  extremely 
scanty,  if  at  all  present.  As  the  nutrition  of  the  epithelium  is  largely 
dependent  upon  the  condition  of  the  submucosa.  lesions  of  this  layer 
influence  the  function  and  structure  of  the  overlying  meml)rane.  Many 
mucous  membranes  possess  lymphoid  tissue,  and,  in  some  locations, 
collections  of  lymiphoid  joUiclcs  constitute  a  distinguishing  feature.  For 
the  most  part  these  nodes  occupy  the  submucosa,  although  in  numer- 
ous situations  the  membrana  propria  contains  a  quantity  of  lymphoid 
tissue.  The  lymphoid  elements  may  be  somewhat  diffuse,  agminated 
in  nodules,  or  grouped  in  patches.  Lymphoid  tissue,  among  other 
functions,  clearly  possesses  antitoxic,  bacteriolytic,  and  possibly  other 
properties  which,  in  the  present  state  of  our  knowledge,  remain  undeter- 
mined. In  certain  infectious  processes,  affecting  the  mucous  mem- 
branes.— for  example,  typhoid  fever — the  most  conspicuous  lesion  in- 
volves, to  the  greatest  degree,  the  lymphoid  elements  of  the  mucous 
membrane. 

Hyperemia  of  a  mucosa  may  be  physiologic;  an  increased  blood- 
supplv  is  sent  to  the  stomach  during  gastric  digestion;  the  uterine  mu- 
cosa is  supplied  with  an  excess  of  blood  during  menstruation.  Patho- 
logic hyperemia  is  usually  a  manifestation  of  irritation  and  is  commonly 
observed  as  a  precursor  of  inflammation.  The  blood  admitted  to  the 
submucosa  is  increased  by  temperature  variations  and  the  presence  of 
poisons  of  strengths  inadequate  to  produce  inflammation;  it  is  possible 
that  vasomotor  influences  may,  in  other  ways,  increase  the  amount  of 
blood  supplied  to  a  mucous  membrane.  The  form  of  pathologic  hyper- 
emia associated  with  inflammation  of  the  mucosa?  will  be  dealt  with 
when  consiilering  that  subject. 

Congestion  of  a  mucous  surface  is  dependent  upon  conditions  that 
interfere  with  the  exit  of  blood  from  the  affected  mucosa.  Congestion  is 
seen  in  the  lungs  and  upper  air-passages  and  in  the  alimentary  canal, 
as  a  result  of  cardiac  flisease  associated  with  interference  in  the  onward 
flow  of  the  blood,  and  in  the  stomach  and  intestinal  mucous  membranes 


542  SPECIAL  PATHOLOGY. 

in  obstructive  hepatic  disease  as  well.  It  may  or  may  not  be  the  pre- 
cursor of  inflammation,  and  its  permanency  is  dependent  upon  the 
condition  that  causes  it.^ 

The  function  of  the  membrane  is  materially  altered  by  the  faulty 
metabolism  that  always  attends  a  stagnant  circulation.  In  time  an 
increase  in  the  fibrous  tissue  of  the  submucosa  occurs,  usually  preceded, 
accompanied,  and  followed  by  a  catarrhal  process  manifested  in  the 
overlying  epithelial  layers.  In  obstructive  diseases  of  the  lungs  or  heart 
the  congestion  of  the  gastric  mucous  membrane  may  be  so  great  as  to 
resemble  the  lesions  resulting  from  poisoning.  The  venous  stasis  some- 
times gives  rise  to  hemorrhage  which  may  be  recurring  and,  although 
usually  slight,  occasionally  is  severe.  If  congestion  be  prolonged, 
varicosity  of  the  submucous  veins  frequently  develops;  rupture  of  such 
varices  may  give  rise  to  alarming  or  even  fatal  bleeding. 

Hemorrhage  from  the  mucous  membrane  occurs  as  a  ph^'siologic 
process  in  menstruation;  hyperemia  and  congestion  not  uncommonly 
terminate  in  hemorrhage,  as  in  yellow  fever,  malaria,  and  allied  condi- 
tions. It  is  not  always  an  evidence  of  a  serious  malady,  as  is  shown 
by  the  occurrence  of  trifling  epistaxis  without  apparent  cause.  In  hemo- 
philia and  scurvy,  epistaxis  is  frequently  present.  As  to  severity,  a 
hemorrhage  may  consist  of  the  trifling  escape  of  a  few  red  corpuscles 
in  an  abundant  mucous  exudate  (serosanguineous)  or  it  may  be  alarm- 
ing; the  escaped  blood  may  pour  out  on  the  surface  as  in  epistaxis,  or  it 
mav  infiltrate  the  submucosa  (interstitial  or  purpuric  hemorrhage) 
and  be  found  postmortem  in  the  intestines  or  elsewhere  as  petechiae, 
ecchymoses,  or  larger  collections  in  the  submucosa.  During  life,  in 
purpura,  exposed  or  visible  mucous  surfaces  may  exhibit  the  discolora- 
tions  in  a  typical  manner.  These  spots,  if  large,  may,  in  very  exceptional 
cases,  terminate  in  necrosis,  and,  if  the  patient  survive,  ulcers  may 
develop,  although  this  is  rare;  as  a  rule,  if  recovery  occur,  the  blood  is 
absorbed  without  any  septic  or  gangrenous  process. 

Atrophy  of  the  mucous  membrane  may  be  an  insidious  process,  due 
to  malnutrition  and  the  action  of  toxic  substances,  or  to  inflammation 
and  sclerosis  of  the  submucosa;  the  epithelium  is  principally  affected. 

Hypertrophy  of  the  mucous  membrane,  in  the  sense  that  there  is  a 
notable  increase  in  the  functional  activity,  is  not  known  to  occur.  In  a 
number  of  conditions  the  thickness  of  the  submucosa  is  conspicuously 
increased  and  occasionally  the  epithelial  layer  is  thickened;  as  a  rule, 
these  changes  are  due  to  irritation  or  inflammation  and  are  not  accom- 
panied by  any  augmentation  in  the  specific  function  of  the  affected 
membrane;  usually  physiologic  activity  is  lessened  or  suppressed. 

IXFILTRATIOX  OF  THE  MUCOUS  MEMBR^AXES-^ 

Pigmentary  Infiltration. — (A)  Pneumoconiosis,  or  pulmonary  pig- 
mentation due  to  extraneous  substances,  assumes  a  number  of  fomis. 
Solid  particles  may  gain  ingress  to  or  through  the  mucous  membrane 
from  the  surface,  as  in  laborers  whose  occupation  exposes  them  to  the 
constant  inhalation  of  suspended  solid  matters:  e.  g.,  the  inhalation  of 
coal-dust  by  miners  leads  to  a  condition  in  the  lungs  known  as  anthra- 
cosis  ;  in  the  grinders  of  metal  instruments,  in  nailers,  etc.,  iron  inhaled 
'See  p.  265.  -See  pp.  231  to  234. 


MUCDl'S   .Mi:.MHU.\Ni:S. 


543 


gives  rise  to  an  allieil  condition,  known  as  siderosis  (when  the  disease  oc- 
curs in  nailers.it  is  also  known  as  na/Vtr'-s-  phtliisis);  in  stone-cutters  and 
the  makers  of  grindstones,  etc.,  the  (Hsease  is  known  aslithosisor  chali- 
cosis.  Similar  infiltrations  occur  in  laborers  in  cotton  and  shoddy 
mills  and  in  the  handlers  of  grain.  These  pigment  particles  do  not  seem 
to  be  able  to  penetrate  the  stratified  epithelium,  but  gain  ingress  further 
down  in  the  air-jiassages;  the  rdvcoli  being  ])ermeable,  the  epithelial 
cells  not  arresting  all  the  i)igment,  it  enters  the  lymph-spaces  of  the 
basement  membrane,  from  which  the  extraneous  substance  diffuses  by 
the  Ivmphatic  channels  into  the  surrounding  tissues.  The  deposited  ma- 
terial finds  lodgment  in  the  following  structures  (Hamilton):  in  the 
subpleural  and  interbronchial  tissues;  in  the  peribronchial  lymph- 
nodes;    in  the  lymphadenoid  interspaces  of  the   alveoli. 

After  the  infiltration  is  well  advanced  in  the  pulmonary  tissues,  the 
substernal  and  general  mediastinal  glamls  are  usually  involved.  Weigert 
has  shown  that  the  circulation  may  be  reached  by  the  ])igment  passing 


Fig.  268. — Section  of  the  Lf.so.  Pneumoconiosis.— (/?i«</^m<-/i.) 
The  deposited  pittnu-nl  is  shown  in  thi-  connective  tissue  of  the  vcsicul.ir  wall. 


through  the  peribronchial  nodes,  which  attach  themselves  to  the  pul- 
monarv  veins,  into  which  they  rupture.  The  presence  of  foreign  solid 
material  induces  inflammation  of  the  mucous  covering — at  first  acute, 
but  from  the  continued  application  of  the  irritant,  the  changes  incident 
to  chronic  inflammation  occur.  In  the  deeper  tissues  fibroid  hyper- 
plasia ensues,  with  the  abundant  production  of  new  fibrous  tissue  in  the 
infiltrated  areas.  The  accompanying  catarrhal  i)rocesses  denude  the  epi- 
thelial protecting  layer,  and  the  lung  tissue  becomes  exposed  to  the  dan- 
gers of  infection  by  bacteria.  The  introduction  of  jiyogenic  organisms 
induces  an  infective  inflammation  which  may  tenninate  in  necrosis,  and 
eventuallv  give  rise  to  cavity  formation;  or,  what  is  much  more  com- 
mon in  susceptible  individuals,  the  tubercle  bacillus  gains  entrance  to  the 
affected  tissues  and  tuberculosis  is  engrafted  on  the  existing  lesions. 
Aside  from  the  lung,  pigmentary  infiltration  is  occasionally  seen  in  the 
vomer  and  turbinated  bones. 


544 


SPECIAL   PATHOLOGY. 


Medicometal  Pigmentation  of  Mucosae. — Occasionally,  metallic  sub- 
stances taken  as  medicines  or  otherwise  may  be  precipitated  in  or  on 
the  mucous  membranes  with  which  they  come  in  contact.  Examples  of 
this  are  seen  after  the  administration  of  iron  and  bismuth. 

(B)  Pigment  Deposit  from  the  Blood. — Brown  induration  of  the  lung 
is  in  part  a  pigmentary  infiltration,  secondary  to  chronic  congestion. 
The  disease  is  most  marked  in  the  lung  in  chronic  heart  disease.  The 
alveolar  epithelium  contains  altered  blood  pigment,  and  pigmented 
cells  are  found  in  the  interalveolar  wall.  The  capillaries  are  distended, 
and  the  fibrous  tissue  of  the  lung  is  increased  in  amount.  The  lungs,  on 
opening  the  chest,  do  not  immediately  retract;  they  are  at  first  brownish- 
red  in  color,  but  on  exposure  to  the  air  they  become  livid  from  the  oxi- 


FiG.  269.    Section  of  Lung  Showing  Chalicosis. — {Schmai4s.) 
a.  Collection  of  infiltrated  material  lodged  in  the  pleura,  c.    A  capsule  of  fibrous  tissue  has  formed  around  it.     a'. 
Similar  nodule  in  the  lung  tissue.     Other  nodules  are  shown,     b.  L^naffected  pulmonary  tissue.      c.  Pleura. 
g.  g.  Blood-vessel,  around  one  branch  of  which  a  nodule  is  forming,     i.  Interlobular  septum,  showing  some 
thickening. 


dation  of  the  excessive  quantity  of  hemoglobin;  as  a  result  of  the  in- 
crease in  fibrous  tissue  the  organs  are  denser  than  normal,  cutting  and 
tearing  with  considerable  resistance. 

Deposition  of  coloring-matter  is  found  in  other  mucous  membranes, 
where  constant  or  repeated  congestions  occur,  as  in  malaria;  the  intes- 
tinal, gastric,  and  hepatic  tissues  showing  the  change  in  the  highest 
degree. 

Fatty  infiltration  seems  exceedingly  rare,  if  it  ever  occurs,  in  a  mu- 
cous surface.  The  author  has  never  seen  it.  It  may  be  present  in 
the  glands  of  the  mucosa. 

Albuminoid  or  amyloid  infiltration,^  when  the  general  disease  is  pres- 

^  See  p.  227, 


MUCOUS   MK.MnKANKS.  545 

ent.  inviules  the  iiuicous  nioinbranc  (subnuuous  hlood-vcssclsj  of  tlic 
stomach  and  intestines,  rarely  the  gullet  or  the  air-[)assaj,'cs. 

Calcareous    infiltration  is  usually  secondary  to  chronic  inllaniniatory 

and  nerrolic  L-haiiucs  in  the  subnnieosa. 


DHGKXICRAriOXS  OF  THE  MUCOUS  MKMBRAXKS. 

Granular  degeneration/  or  cloudy  sivclliug,  occurs  in  the  various 
epithelial  structures  as  the  result  of  infection  of  the  mucosa  or  the 
action  of  bacterial  toxins  reaching:  the  epithelium  throuj^di  the  blood. 
The  condition  has  also  been  attributeil  to  hij^d^  temperature  and  to  vari- 
ous autointoxications.  The  affected  cells  are  granular,  the  nuclei 
obscured,  and  desquamation  hastened.  Granular  degeneration  accom- 
jianies  necrosis  and  all  forms  of  inflammation  attacking  mucous  mem- 
branes. 

Fatty  degeneration,'-  or  fatty  metamorphosis,  representing,  as  it  does, 
a  later  stage  of  the  granular  process,  will  be  seen  when  the  latter 
condition  has  persisted  for  a  time  with  continuing  or  progressively 
increasing  causes.      It  has  been  noted  in  pernicious  anemia. 

Coagulation  necrosis''  affecting  mucous  membranes  is  not  materially 
different   from   the  same  process  occurring  elsewhere.     It  may  be  in- 


#■ 


Hit 


<\i^- 


I'n..     170.       (■!    \'  1'!      1  M  KA-  ill..     271. l-AllV      l)tt.h.ShKAlHiN  ln;.      2-2.      (JKA.NVI.AK      IJKCKNER- 

TiDN  (Cloi-dy  Swellim;)  of  of    the    Liver    Cells. —  ation  of    the    Kin.SEY    En- 

THE  Liver  Cells. — (Schmuus.)  (Schmaus.)  thelilm  (Cloudy  Swelling). 

— (Sclimniis.) 

duced  by  chemic  agents,  such  as  lactic  acid,  and  is  sometimes  due  to 
contact  with  heat.  A  similar,  but  probably  not  identical,  process  re- 
sults from  the  action  of  necrosing  poisons,  such  as  strong  alkalies  and 
concentrated  acids  The  usual  cause  of  coagulation  necrosis,  as  observed 
on  mucous  membranes,  is  infection;  the  most  typical  form  of  the  lesion 
is  observed  in  mucosa?  attacked  by  the  diphtheria  bacillus.*  The  typhoid 
ulcer  is  in  part  the  result  of  coagulation  necrosis  affecting  the  patches 
of  Peyer.  The  streptococcus,  pneumococcus,  and  sometimes  other  infec- 
tions give  rise  to  this  form  of  necrosis. 

Morbiil  Anatomy. — On  the  mucosic.  ])articularly  that  of  the  pharynx, 
coagulation  necrosis  may  be  restricted  to  an  exudate  forming  on  the 
surface,  constituting  what  is  sometimes  called  a  false  membrane.  In 
the  presence  of  more  intense  irritation,  as  by  diphtheria  bacilli  of  rela- 

'  See  p.  247.  '  See  p.  242.  '  See  p.  251. 

*  See  p.  iiS  and  examine  Fig.  67,,  p.  120. 

.^6 


546 


SPECIAL  PATHOLOGY. 


lively  high  virulence,  the  necrosis  extends  into  the  submucosa  or  occa- 
sionally deeper.  Histologically  the  structure  is  composed  of  a  matrix 
in  which  fibrin  is  often  conspicuous;  epithehal  cells  and  leukocytes 
are  commonly  abundant.  Where  the  lesion  extends  into  the  sub- 
mucosa, separation  of  the  necrotic  material  results  in  the  formation  of  an 
ulcer,  the  size  of  which  corresponds  to  the  extent  of  the  necrotic  process. 
The  condition  is  most  frequent  in  the  pharynx,  and  in  pseudomem- 
branous inflammation  of  the  larynx,  trachea,  and  bronchi;  it  also 
occurs  in  certain  infections  of  the  intestine. 

INFLAMMATION  OF  THE  MUCOUS  MEMBRANES. 

There  is  probably  no  tissue  in  the  body  so  prone  to  inflammatory 
processes  as  the  mucous  membranes,  and  since  these  inflammations  occur 
as  the  result  of  many  and  complex  causes,  and  are  modified  by  the  char- 
acter of  the  membrane,  as  well  as  by  its  function  and  by  the  cause,  to 
describe  each  anatomic  and  etiologic  form  would  require  more  time  and 
space  than  is  allotted  to  the  present  volume.  For  convenience  of  de- 
scription the  inflammations  are  divided  into  the  (i)  catarrhal,  (2) 
pseudomembranous,  (3)  hemorrhagic,  (4)  gangrenous,  (5)  suppurative, 
and  (6)   chronic  infectious. 

Catarrhal  inflammation  of  the  mucous  membranes  may  be  acute 
or  chronic.  The  former  is  usually  of  brief  duration  and,  unless  excep- 
tionally severe,  does  no  irreparable  damage  to  the  affected  mucosa. 
The  chronic  process  is  of  indefinite  duration,  usually  begins  in  the  acute 
or  a  succession  of  acute  attacks,  or,  in  some  cases,  insidiously.  If  at 
all  intense  or  prolonged,  as  is  usually  the  case,  permanent  changes  are 
produced  in  the  tissues  involved. 

Acute  catarrhal  inflammation  arises  as  a  result  of  many  complex 
causes  applied  from  without  or  exerting  their  influence  from  the  cir- 
culatory side  of  the  membrane.  The  process  is  practically  always  a 
manifestation  of  infection,  although  predisposition  has  no  little  influence 
in  determining  the  character,  duration,  and  other  essential  phenomena 
of  the  lesions.  Nearly  all  the  acute  infectious  diseases — such  as  measles, 
scarlet  fever,  typhus  fever,  diphtheria,  etc. — are  accompanied  by,  or 
may  incite,  a  catarrhal  inflammation  of  one  or  more  mucous  surfaces; 
the  same  is  true  of  the  chronic  infections,  such  as  tuberculosis  and 
syphilis,  when  they  affect  a  mucous  membrane. 

The  application  of  other  irritants  to  the  mucous  surface  is,  next 
to  infection,  the  most  common  cause,  and  embraces  a  multitude  of 
subcauses:  c.  g.,  foreign  bodies;  contact  of  the  mucosa  with  heat,  in 
the  form  of  hot  air,  steam,  or  a  liquid  such  as  hot  water;  irritant  gases, 
as  chlorin,  bromin,  ammonia,  sulphurous  acid;  poisons,  such  as  escha- 
rotics  like  the  mineral  acids,  arsenic,  etc.,  in  dilutions  too  weak  actually 
to  induce  necrosis  of  the  surfaces  with  which  they  come  in  contact. 
Inflammatory  conditions  in  the  mucosa  may  also  arise  from  irritants  due 
to  chemic  changes  in  foods,  whether  the  irritant  be  preformed  when 
the  food  is  taken  or  develop  subsequently  by  fermentation  or  other 
change;  as  examples  of  these  may  be  mentioned  ptomain  poisoning 
and  gastric  catarrh  due  to  the  ingestion  of  decomposing  or  fermenting 
foods.     Alcohol  is  also  a  cause. 

While  rapid  thermic  and  barometric  changes  and  excessive  humid- 


Ml'Cdl'S    Mi:.MMkA\Ii:S.  547 

ity  are  alleged  causes,  they  probably  act  by  altering  the  secreticiii  or 
circulation,  or  both,  thereby  lessening  the  normal  resistance  to  infec- 
tion; it  is  not  im])robal)le  that  many  of  the  i)reviously  given  causes 
act  in  a  similar  manner.  Pure  mycoses  of  the  mucovis  surfaces  mav  in- 
cite a  catarrhal  iiiHammation,  often  violent  in  character;  as  an  example 
of  mycotic  infection,  a])parently  restricted  to  the  mucous  membrane, 
thrush  is  most  frequently  cited.  Bright's  disease,  rheumatism,  gout, 
and  allied  diseases  may  be  causes  or  ])rcdisposing  factors.  The  young 
and  the  aged,  more  than  those  in  middle  life,  seem  susceptible  to  dis- 
eases of  the  mucous  membranes. 

The  foregoing  is  intended  to  indicate  types  of  causes  f)f  mucous 
membrane  inflammation,  and  is  in  no  way  a  catalogue  of  the  possible 
etiologic  factors.  The  same  cause  rarely  gives  rise  to  inflammation  of 
a  number  of  mucosae  simultaneously,  although  it  may  possess  the 
power  to  do  so.  It  has  been  demonstrated  that  the  pneumococcus  may 
produce  conjunctivitis,  rhinitis,  jdiaryngitis,  tracheitis,  bronchitis,  and 
pneumonia,  and  also  that  it  may  attack  the  alimentary  mucosa,  endo- 
metrium, and  Fallopian  tubes.  As  a  rule,  however,  it  aff^ects,  at  one 
time,  continuous  mucous  membranes  only.  Another  fact  to  be  borne 
in  mind  in  connection  with  catarrhal  inflammations  is  that,  no  matter 
what  the  type  of  inflammatory  lesion  affecting  a  mucous  membrane, 
there  is  practically  always  an  associated  catarrhal  process.  Typhoid, 
cholera,  and  dysentery  frequently  induce  other  lesions,  but  a  catarrhal 
inflammation  of  the  intestinal  mucosa  is  essentially  always  present. 
In  the  pharynx  and  larynx,  less  frequently  in  the  nose,  the  diphtheria 
bacillus  is  capable  of  ])roducing  extensive  necrosis,  false  membrane, 
even  hemorrhagic  inflammation,  but  with  all  of  these  a  varying  degree 
of  catarrh  occurs. 

Morbid  Anatomy. — In  acute  catarrhal  inflammation  of  any  mucous 
membrane,  it  is  practically  always  possible  to  recognize  three  stages; 
in  the  first,  sometimes  called  the  dry  staiic,  or  stage  of  hyperemia,  the 
secretion  is  lessened;  in  the  second,  known  as  the  exudative  stas^e,  the 
discharge  from  the  mucosa  is  more  abundant  than  normal,  a  peculiarity 
justifying  the  name  acute  catarrh,  sometimes  used  for  the  ])rocess; 
the  third  stage,  in  favoraiilc  cases,  constitutes  the  jieriod  in  which 
regeneration  and  restoration  to  the  normal  occur. 

In  the  flrst  stage  of  the  inflammation  the  surface  is  dry,  or  is  lightly 
covered  by  a  thick,  sticky,  adherent  mucus;  during  life  hyperemia  is 
shown  by  the  intense  redness,  which,  in  violent  cases,  may  assume  a 
dusky  reil;  a  little  later  is  added  evident  submucous  edema,  due  to 
the  hyperemia  and  progressing  exudation  of  serum  in  the  submucosa. 
The  histologic  changes  of  this  stage  are  engorgement  of  the  submucous 
vessels  and  infiltration  of  the  submucosa  with  scrum  and  leukocytes; 
the  epithelium  is  cloudy  and  swollen,  and  beginning  descjuamation  is 
usually  evident.  The  morbid  physiology  is  shown  in  excessive  dryness, 
giving  rise,  in  the  vocal  organs,  to  the  husky,  rough  voice  or  to  a  cough; 
in  the  nose,  to  the  "stopped-up"  feeling,  which  is  intensified  by  the 
erectile  tissue  becoming  far  more  distended  by  blood  than  is  possible 
in  mucosae  containing  no  such  structure;  in  the  stomach,  the  absence 
of  secretion  causes  anorexia  and  nausea,  and  in  the  intestines,  consti- 
pation. 

Immediatelv  following  the  first  or  dry  stage — which  may  be  brief 


548 


SPECIAL  PATHOLOGY. 


or  unusually  prolonged,  rarely  the  latter — an  abundant  discharge  from 
the  affected  mucosa  occurs.  The  epithelial  cells  desquamate  with  the 
greatest  rapidity,  and  the  surface,  instead  of  being  dry  and  sticky, 
becomes  flooded  with  mucus.  The  rapidly  exfoliating  cells  undergo 
granular  and  fatty  degeneration,  necrosis,  and  desquamation  with  such 
promptness  that  the  special  secretion  of  the  part  is  not  elaborated: 
e.  g.,  in  the  stomach,  pepsin  production  is  arrested;  in  the  salivary 
glands,  there  is  a  lessened  output  of  digestive  ferment,  and  the  pro- 
duction of  mucus  is  excessive.  The  mucous  membrane  may  fail  to 
produce,  even  in  small  quantities,  the  agent  which  normally  it  is  the 
function  of  the  mucosa  to  elaborate;  the  apepsia  of  gastritis  may  be 
taken  as  illustrating  this  functional  inadequacy  of  an  inflamed  mucous 
membrane.  The  inflammatory  discharge  is  composed  of  the  debris 
resulting  from  necrosis  and  consequent  fragmentation  of  the  epithelium, 
a  varving  quantitv  of  serum,  epithelial  cells,  free  nuclei,  and  leukocytes; 
more' or  less  of  the  serum  infiltrating  the  submucosa  passes  through 
the  basement  membrane,  and  may  be  sufficient  in  quantity  to  justify 
calling  the  inflammation  serous;  in  very  severe  cases  many  red  blood- 
corpuscles  escape. 

The  patient  is  usually  relieved,  the  submucous  circulation  being 
re-established  and  the  perivascular  exudate  finding  some  exit  by  the 
surface  and  the  lymphatics.  If  the  cause  be  now  withdrawn,  the  cir- 
culation gradually  returns  to  the  normal,  absorption  of  the  submucous 
exudate  is  completed,  and  restoration  of  the  epithelial  covering  from 
the  genetic  laver  of  the  basement  membrane  gradually  takes  place. 
Ulceration  rarely  occurs.  The  basement  membrane  is  probably  never 
destroyed  by  a  simple  catarrhal  process;  when  such  destruction  results, 
it  is  most  likely  that,  during  the  hyperemic  stage,  stasis  occurred  in 
some  of  the  vascular  twigs  and  by  the  occurrence  of  coagulation  ne- 
crosis in  the  affected  area,  an  ulcer  resulted. 

The  restoration  of  the  mucosa  is  usually  complete  and  the  return 
of  function  is  satisfactory.  It  is  generally  maintained  that  a  mucous 
membrane  once  subjected  to  a  catarrhal  disturbance  is  rendered  more 
susceptible  to  subsequent  attacks.  In  some  cases,  the  cause  continuing 
to  act,  the  process  is  gradually  converted  into  a  chronic  catarrh;  in 
other  instances  rapidly  repeated  acute  inflammations  induce  structural 
alterations  in  the  mucosa  and  lay  the  foundation  for  a  more  chronic 
lesion. 

Chronic  catarrhal  inflammation  of  a  mucous  membrane  results  from 
the  continuance  of  the  last  stage  of  the  acute  condition  or  eventually 
persists  after  a  succession  of  acute  attacks.  The  chronic  inflammations 
are  due  to  causes  which  persist — practically  always  an  infection — and 
are  rendered  possible  by  antecedent  or  concurrent  conditions,  influenc- 
ing the  mucosa  locally  or  lessening  the  bacteriolytic  and  allied  properties 
of  the  body-juices:  e.  g.,  the  slowed  circulation  of  chronic  heart  dis- 
ease, the  vascular  and  blood  changes  of  Bright 's  disease,  gout,  rheu- 
matism, malaria,  chronic  alcoholism,  etc.,  by  weakening  the  resistance 
of  the  mucous  surface,  favor  repeated  attacks  of  infection  or  the  per- 
sistence of  a  single  attack  once  developed.  The  continued  presence 
of  nonbacterial  irritants  also  exerts  a  deleterious  influence  on  the  af- 
fected tissue  and  impedes  the  processes  by  which  infection  is  combated 
and  restitution  of  the  normal  accomplished.      Such  influences  are  shown 


MUCOUS   MH.MHkANKS.  549 

in  tlic  chronic  nasal  catarrhs  associatetl  with  the  iircsence  of  foreij^n 
bodies;  constant  exposure  to  irritating  dusts  and  fumes  is  attended 
bv  similar  consequences.  Repeated  libations  also  weaken  the  mucous 
membrane. 

Mortyid  A)UJtonty. — The  continued  infiltration  of  the  submucosa  with 
leukocytes  and  serum  leads  to  ])crmanent  alterations  in  tissue.  Pro- 
liferation of  the  ti.xed  connective-tissue  cells  j:[ives  rise  to  fibrous  tissue, 
which,  at  first,  is  cellular,  but  later  the  cells  become  less  abundant  and 
contraction  occurs.  These  changes  alter  the  nutrition  of  the  submucosa, 
lessen  its  blood-supply,  and  exert  a  deleterious  influence  on  the  over- 
Iving  epithelium.  During  the  earlier  stages  the  superabundance  of  the 
submucous  inflammatory  products  gives  the  membrane  an  appearance 
of  thickening,  and  is  often  spoken  of  as  an  evidence  of  hypertrophy, 


-f^: 


Kir..     J7V    ->HTIi>N    (If     W  AI  I.    iiF     HkhncIUS      C'hKiiMi      l>Kci>c|Iin- 

Specimen  hardeni-d  in  corrosive  suMimatc.  intiltrau<l  with  jiaraftin.  stainoi  with  hematoxylin  and  c-osin,  and 
mounted  in  balsam.  (From  slide  prepared  by  Professor  Harris.)  a.  Di.igrammatic  representation  of  the 
normal  cylindric  cells  arranKe<l  as  in  health,  b.  The  line  runs  just  under  the  membrana  propria  into  a  mass 
of  newly  formed  librous  tissue,  which  extends  downward  to  c  Just  beyond  the  line  from  c  are  several  blood- 
vcssi-ls  distende<l  bv  blotxl.  d.  Mucous  gland  surrounded  by  considerable  libroid  thickt-nint?  of  the  submucosa. 
e.  Cartilage.  /.  Distended  blood-vessel,  g.  Part  of  the  chronically  inflamed  mucosa,  showing  inflam- 
matory exudate  and  proKressive  librosis  of  the  submucosa.  The  normal  cylindric  cells  lh.it  should  cover 
the  area  have  desquamated,  and  those  remaining  are  im[x-rfectly  formed  and  des'iuamating.  To  the  left  of  the 
lower  end  of  the  line  from  g  (1.5  cm.)  is  a  depression  which  marks  the  exit  fxiint  of  a  duct  from  one  of  the 
mucous  glands  h.  Denudc-d  surface  of  the  mucosa.  Lnder  this  point  the  more  recent  inflammatory  changes 
are  less  marked   than  at  g.     (J-inch  objective    i-inch  ocular.) 

or  the  inflammation  is  said  to  be  hypertrophic;  the  persistent  softened 
condition  of  the  tube  may  favor  dilatation  in  this  stage.  Occasionally, 
from  obstruction  of  ducts,  mucous  glands  and  follicles — as  in  the  mouth, 
pharvnx.  and  trachea — become  distended  and  conspicuous.  The  prom- 
inence of  these  structures  has  given  to  the  process  the  name  follicular 
inflammation.  In  other  cases  the  lymphoid  tissue  is  the  seat  of  im- 
portant alterations;  the  lymph-sinuses  are  distended,  the  endothelial 
cells  ])roliferate,  and  an  accumulation  of  leukocytes  in  the  interior  of 
the  nodule  occurs.  As  a  result  of  these  changes  the  lympiuiid  follicle 
enlarges  and  may  often  be  recognized  as  a  distinct,  slightly  indurated, 
or  soft  node  in  the  affected  mucosa.  Failure  on  the  part  of  the  earlier 
observers  to  differentiate  between  the  enlarged  lymphoid  follicles  and 


550  SPECIAL   PATHOLOGY. 

the  distended  mucous  glands  resulted  in  both  processes  being  called 
follicular  inflammations. 

As  the  inflammatory  process  advances, — grows  older, — contraction 
of  the  newly  formed  submucous  tissue  ensues,  leading  to  lessened  blood- 
supplv  to  the  surface  and  to  faulty  or  perverted  function  of  the  mucous 
membrane,  associated  with  thinning — an  atrophy,  giving  the  present 
stage  the  name  atrophic  iuflanunation;  the  absence  of,  or  diminution  in, 
secretion  justifies  the  name  dry  catarrh,  sometimes  given  to  the  aft'ec- 
tion.  The  hypertrophic  and  atrophic  stages  of  the  inflammation  may  be 
seen  in  the  same  subject  at  the  same  time,  or  the  atrophy  may  be  ob- 
served to  follow  the  chronic  inflammation  without  the  development 
of  very  marked  thickening,  contraction  exceeding  in  rapidity  the  process 
of  infiltration.  Whatever  may  have  been  the  cause  of  the  inflamma- 
tion, the  bacteria  of  decomposition  find  lodgment  in  the  dry  and  slowly 
removed  secretion,  and  fetid  or  poisonous  products  are  developed.  This 
is  illustrated  in  ozena  and  in  neglected  chronic  inflammations  of  the  ear. 

Catarrhal  inflammation  may  occur  on  any  mucous  membrane.  Of 
course,  the  accident  of  location  gives  rise  to  dift'erences  in  the  character 
of  the  lesion,  but  the  essential  phenomena  will  be  but  variations  of  the 
stages  and  processes  indicated.  The  site  and  name  for  some  of  the 
accompanying  catarrhal  processes  are  as  follows:  Nose,  rhinitis;  mouth, 
stomatitis;  tongue,  glossitis;  tonsils,  tonsillitis;  pharynx,  pharyngitis; 
trachea,  trachitis  or  tracheitis;  bronchus  or  bronchi,  bronchitis;  in  the 
capillary  bronchi  and  the  air  vesicles,  catarrhal  pneumonia  (a  condition 
in  w^hich  the  catarrhal  inflammation  differs  from  that  observed  in  other 
localities  in  the  tendency  to  accumulation,  in  changes  in  the  inflamma- 
torv  products,  and  in  other  phenomena,  which  demand  that  the  process 
be  considered  more  in  detail,  as  will  be  done  when  the  forms  of  pneu- 
monia are  described);  esophagus,  csopJiagitis;  stomach,  gastritis,  or,  on 
account  of  the  altered  secretion  and  consequent  symptoms  of  indigestion, 
dyspepsia;  ileum,  ileitis;  colon,  colitis;  ileum  and  colon,  ileocolitis;  rectum 
and  mucous  surface  of  the  anus,  proctitis;  urethra,  urethritis  (when  due 
to  the  gonococcus  and  involving  the  urethra,  the  process  is  called  gonor- 
rhea; the  same  cause  acting  on  other  mucosae  produces  what  is  termed 
gonorrheal  inflanimation);  bladder,  cystitis;  ureter,  ureteritis;  pelvis  of 
the  kidnev,  pyelitis;  gall-bladder,  cholecystitis;  biliary  ducts,  cholangitis. 
Catarrhal  inflammation  occurs  no  doubt,  in  the  hepatic  structure,  but 
here,  as  in  the  lung  and  kidney,  other  associated  phenomena  require  that 
the  condition  be  considered  separately. 

Pseudomembranous,  Fibrinous,  Plastic,  or  Croupous  Inflammation. 
— Of  the  many  names  given  to  this  condition,  the  first-mentioned  is 
preferable.  The  process  consists  of  an  inflammation,  attended  by  the 
development,  external  to  the  membrana  propria,  of  a  false  or  pseudo- 
membrane  composed  of  a  solid  or  semisolid  matrix  and  entangled  cell 
elements. 

Ca^ises. — That  pseudomembranous  inflammations  can  be  induced 
without  the  intervention  of  bacteria  is  established,  but  that  such  is  often 
the  case  is  extremely  doubtful.  Heat,  irritant  gases,  such  as  chlorin  and 
ammonia,  escharotics  which  do  not  destroy  the  basement  membrane,  and 
allied  agents,  may  possibly  give  rise  to  inflammations  attended  by  the 
development  of  false  membrane.  The  local  application  of  lactic  acid 
and  other  medicaments  is  sometimes  followed  by  pseudomembrane  for- 


MUCOUS    M  KM  M  RANKS. 


551 


niation.  Of  the  main-  inicrobic  (.-auses.  a  few  arc  estat)lislKMl  aii<l  deserve 
special  mention.  In  the  nose,  pliar\iix,  and  air-passa^cs  the  ])rocess  is 
usually  due  to  the  dii)hthcria  bacillus,'  less  frc(iuently  to  the  strepto- 
coccus.- and  occasionally  to  the  i)neumococcus.-'  Cases  of  i)seudomcni- 
branous  inflammation  have  been  observed  in  which  the  bacillus  of 
Friedlander*  was  the  only  orj,'anism  present.  The  pyoj^enic  staphylo- 
cocci'' are  rarelv  the  cause.  Anionic  the  less  frecjuent  orj^'anisms  may  be 
mentioned  the  influenza  bacillus,"  the  colon  bacillus,^  tyjihoid  bacillus.* 
and  the  bacillus  of  ilysentery."  The  ulceromembranous  stomatitis  or 
an«;ina  oi  Vincent'"  is  sometimes  attended  by  the  ff)rmation  of  pseudo- 
membrane.  Investit,^1tion  into  the  cause  of  pseudomembranous  rhinitis, 
which  often  lasts  for  months,  has  demonstrated,  in  a  larj^'e  ])ercentaj,'e 
of  cases  the  ]iresence  of  the  Bacillus  dij^htheria?.  It  would,  therefore, 
appear  that  the  chronic  as  well  as  the  acute  pseudomembranous  inflam- 
mations are  frequently  due  to  the  Klebs-Loffler  bacillus.  Pseudomem- 
branous inflammation  of  the 
intestine  has  been  observed 
in  pyemia  and  allied  septic 
conditions;  also  in  pneumonia 
anil  tyi)hoid  fever,  as  well  as 
in  Bright's  disease,  cirrhosis 
of  the  liver,  and  cancer.  A 
pseudomembranous  bron- 
chitis" sometimes  accom- 
panies pulmonary  tuberculo- 
sis and  occasionally  arises 
independent  of  any  known 
cause;  it  is  probably  always 
of  bacterial  origin. 

Morbid  A  mitomy. — Two 
forms  are  recognized — an 
acute  and  a  chronic;  so  far 
as  known,  the  histology  and 
process  of  development  dififer 
onlv  in  that  the  chronic  form 
occupies  more  time.  Of  ne- 
cessitv,  the  process  begins  as 

a  catarrhal  inflammation,  with  hyi)eremia  and  infiltration  of  the 
submucosa;  liquor  sanguinis  passes  through  the  liasement  membrane, 
and,  reaching  the  surface,  the  necessary  ferment  is  supplied  by 
the  bacteria  or  the  epithelial  cells  (probably  the  latter,  as  bac- 
teria may  be  introduced  into  the  circulation  of  an  animal  without 
immediate  coagulation  of  the  blood),  and  coagulation  occurs.  Some- 
times the  membrane  contains  a  few  red  blood-cells,  which  occa- 
sional! v  are  sutliciently  numerous  perceptibly  to  tinge  the  exudate; 
rarely  hemorrhage  into  the  membrane  is  conspicuous.  That  all 
pseudomembranous  processes  are  due  to  the  deposition  of  a  fibrin- 
forming  bodv  has  been  strongly  controverted.  Wagner  contended 
that  the  pseiidomembrane  results  from  a  fibrinous  or  croupous  meta- 

'  See  p.  iiS.        'Sec  p.   114-        'Seep.  loo-  'See  p.   127.        *  Si-e  p.  113. 

•Seep.  126.       'See  p.  1156.       'Seep.  13Q.  »  See  p.  141.      "See  p.    172. 

"  A  tijixire  illustratin.ij  this  condition  will  be  found  tn  the  article  on  pulmonary- 
tuberculosis. 


lu..  274.     .Maki.i.s  UK  ISkldomkmbkank  from  Tonsil,  Ca.sk 

OF    DlPHTHKRlA. 

.1,  .1.  Diphthcri.i  liarilli;  the  ixiintir  from  the  lower  A  cnd.s  in 
an  .-irea  of  uranular  matcriiil.  B.  Cotti.  C.  Strands  of 
fibrin.  The  ivlUilar  cli-nnnts  prisint  are  s<|uamous  epi- 
thelium, and  |K)lyniorph<>nuilear  and  hyaline  lfiikor\-tes. 


552 


SPECIAL  PATHOLOGY. 


morphosis  of  the  epithelivim  associated  with  degenerative  changes  in 
the  cell  nuclei.  As  Baumgarten^  has  shown,  the  changes  described  by 
Wagner  are  frequently  easily  detected,  and  it  may  be  possible  that  some 
of  the  membranes  are  formed  in  the  way  suggested.  It  has  also  been 
shown  that  the  membrane  may  contain  mucin,  and  that  it  often  fails  to 
give  the  characteristic  stain  reaction  of  fibrin  (p.  252).  It  must  not  be 
forgotten  that  on  various  mucosas  rapid  alteration  in  the  fibrin  may  occur, 

and  that  digestive  auto- 
ly  tic  or  like  changes  may 
rob  it  of  its  specific 
stain  reactions.  The 
fact  that  mucin  is  pres- 
ent in  the  membrane  is 
not  astonishing  when 
the  frequent  entangle- 
ment of  epithelial  cells 
containing  this  body  is 
considered.  Still,  it 
must  be  admitted  that, 
with  the  tests  at  our 
disposal,  membranes  ap- 
parently mucigenous 
and  failing  to  give  the 
fibrin  reactions  often  oc- 
cur; that  fibrin  had  no 
part  in  their  formation 
is  not  so  easily  estab- 
lished. 

The  membrane  may 
be  fibrillar, — that  is,  the 
fibrin  coagulated  in  fib- 
rillae,  or  branching  lines, 
— or  the  result  of  the 
coagulation  may  be  a 
hyaline,  homogeneous 
film,  alm_ost,  if  not  quite, 
imperceptible.  If  the 
exudate  be  fibrillar,  the 
membrane  is  clearly  dis- 
cernible during  life;  if 
hyaline,  it  may  be  quite 
invisible,  even  in  the 
throat.  Intermediate 
between  the  fibrillar  and 
hyaline  forms  of  the 
membrane  is  a  finely  granular  deposit,  resembling  to  a  certain  extent 
fragmented  cells  rather  than  a  distinct  fibrinous  product.  The  hyaline 
and  granular  fonns  of  the  membrane — particularly  the  hyaline — resem- 
ble in  stain  reactions  similar  mucin-containing  structures.  The  mem- 
brane may  be  laminated,  especially  in  chronic  cases;  two,  three,  or  even 

*  The   essential   facts   concerning  this  process  may  be   gleaned   from   Baum- 
garten's  paper,  in  the  "Berl.  klin.  Wocli.,"  1897. 


Fig.  275.  -  Vi,kii(_al  bi,ciiij.\  through  the  Pseudomembrane  and 
Part  of  the  Wall  of  the  Larynx  in  Pseudomembranous 
Laryngitis. — (Schmaus.) 

a.  Cartilage,  b.  Submucosa,  rich  in  glandular  elements,  also  swollen 
and  with  some  lymphoid-cell  exudate,  c.  Line  of  the  membrana 
propria,  d.  Pseudomembrane  made  up  of  fibrinous  elements,  in 
which  are  entangled  leukocytes  and  desquamated  fragmented 
epithelial   cells,    e,   e.  Gland-duct. 


MUCOrS   MKMBkANKS, 


5S.> 


four  ilistiiut  layers  may  he  shown  on  section.  Stmiclinics  these  layers 
do  not  adliere  to  one  another  and  may  be  separated  or  separable;  the 
lamination  is  probably  due  to  a  layer  of  membrane  fomiing,  followed  bv 
a  pause,  during  which  a  small  (juantity  of  mucus  accumulates  below, 
and  then  a  second  layer  of  membrane  forms  and  another  layer  of  semi- 
liquid  exudate,  ami  so  on,  until  the  cavity  is  freed  of,  or  is  filled  l)V,  the 
rapidly  forming  mass. 

Occasionally,  a  rather  extraordinary  periodicity  is  observed  in  the 
appearance  of  the  momlirane;   this  is  especially  true  of  the  chronic  form. 


Fic.  376. — FiBRixors  Cast  from  the  Bronthi.  Cvse  of  Croctocs  PxEmoxiA.'— <5  Am<iM.t.) 

in  which,  exclusive  of  the  pseudomembranous  processes  that  may  accom- 
pany menstruation,  the  membrane  appears  once  each  week,  once  each 
month,  or  at  other  stated  inters'als.  Its  appearance  may  be  attended 
by  fever  or  other  symptoms;  in  the  acute  pseudomembranous  inflamma- 
tions this  always  occurs,  but  in  the  chronic  types  no  symptoms,  except 
the  expulsion  of  the  membrane,  may  {)recede,  accompany,  or  follow  its 
formation.  Exfoliation  or  casting-off  of  the  membrane  may  occur  as 
'  Pneumonia  is  not  a  frequent  cause  of  fibrinous  bronchitis. 


554  SPECIAL  PATHOLOGY. 

rapidly  as  it  forms,  or  it  may  remain  and  be  pushed  off  by  developing 
mucus  or  continued  functional  activity.  When  removed,  the  surface 
of  the  basement  membrane  is  exposed;  but  that  tissue  is  not  destroyed, 
and  the  pseudomembrane  may  be  immediately  reproduced,  or,  if 
the  process  be  in  a  condition  to  terminate — the  cause  withdrawn — a 
catarrhal  inflammation  of  the  mucous  surface  ensues,  and  recovery  fol- 
lows exactly  as  in  simple  acute  catarrhal  inflammations.  In  chronic 
cases  the  tendency  to  recurrence  of  the  process  is  manifested  by  repeated 
attacks,  as  in  membranous  endometritis,  relapsing  fibrinous  bronchitis, 
and  membranous  proctitis.  Of  the  chronic  form  occurring  in  the 
bronchi  Osier  says,  "We  know  of  nothing  which  can  prevent  recurrent 
attacks." 

Sites. — There  is  no  anatomic  reason  wdiy  pseudomembrane  should 
not  occur  wdierever  catarrhal  inflammation  may  develop.  The  acute 
pseudomembranous  process  is  most  frequent  in  the  larynx,  throat 
and  nose,  intestine,  rectum,  and  middle  ear,  in  the  order  named;  the 
chronic  form  is  most  common  in  the  uterus,  rectum,  bronchi,  nose,  and 
intestine,  in  the  order  given. 

Hemorrhagic  inflammation  of  mucous  membranes  is  relatively 
rare.  It  accompanies  intense  infective  processes  and  may  be  regarded 
as  a  manifestation  of  infection  by  intensely  virulent  bacteria  or.  as 
the  result  of  lowered  resistance  on  the  part  of  the  patient.  The  condi- 
tion probably  does  not  merit  a  separate  consideration,  as  it  is  nothing 
more  than  one  of  the  previously  described  processes,  or  of  gangrenous 
inflammation,  accompanied  by  the  presence  of  hemorrhage.  Inflam- 
mations of  this  character  may  accompany  diphtheria  and  diphtheroid 
anginas  and  the  throat  lesions  of  scarlet  fever.  It  is  also  one  of 
the  conspicuous  manifestations  of  dysentery.  Inflammation  of  this 
type  is  observed  in  mucous  membrane  lesions  that  sometimes  ac- 
company acute  septic  processes  such  as  puerperal  fever  and  other 
forms  of  septicemia  and  also  pyemia.  In  some  cases  of  peritonitis,  espe- 
cially the  fulminating  septic  form,  an  associated  hemorrhagic  inflam- 
mation of  the  colon,  and,  less  frequently,  of  the  small  intestine  and 
bladder,  is  sometimes  observed.  Inflammation  attended  by  capillar}^ 
hemorrhage  may  follow  the  application  of  escharotics  and  sometimes 
accompanies  certain  types  of  poisoning;  hemorrhagic  gastritis  due  to 
arsenic,  carbolic  acid,  and  other  irritant  poisons  belongs  with  this  group. 
The  condition  is  to  be  differentiated  from  hemorrhage  due  to  erosion, 
necrosis,  or  other  lesion  involving  an  artery  or  vein.  In  the  latter 
group  of  cases,  which  includes  bronchopulmonary  hemorrhage,  bleeding 
from  gastric  and  typhoid  ulcers,  and  allied  conditions,  the  hemorrhage 
is  from  a  vessel  of  some  size;  in  the  hemorrhagic  inflammations  the 
quantity  of  blood  is  rarely  large  and  is  derived  from  capillaries,  the  w^alls 
of  whicii  have  been  injured  by  the  toxic  agent  to  which  the  associated 
inflammatory  process  is  due. 

Morbid  Anatomy. — As  already  stated,  hemorrhagic  inflammation  is 
usually  a  complication;  the  affected  tissues  manifest  the  histologic 
changes  of  catarrhal,  pseudomembranous,  or  gangrenous  inflamma- 
tions, and,  in  addition,  are  infiltrated  by  erythrocytes  which  have  been 
extravasated  from  the  injured  capillaries.  The  affected  membrane  is 
blood-stained,  the  color  varying  from  a  pinkish-red  to  a  dark  crimson 
and  in  some  cases  purple  or  purplish-black.     The  surface  is  often  strewn 


Ml'COUS   MlCMUkANKS. 


555 


with  small  shretKly  coa.yula,  and  similar  bodies  are  also  present  in  the 
discharges.  The  hemorrhage  is  rarely  abundant,  although  I  recall  an 
instance  of  hemorrhagic  enterocolitis,  due  to  combined  ])uer{)eral  sepsis 
and  poisoning  by  intrauterine  mercurial  ilouches,  in  which  the  stools 
indicated  large  hemorrhages  and  led  to  the  suspicion  of  typhoid  ulc-era- 
tion.  At  the  autopsy  the  intestine  was  distended  by  almost  pure  bloo<l, 
although  at  no  yioint  could  any  alteration  resembling  an  ulcer  be  detected. 
Histologically  the  changes  of  pseudomembranous,  or  more  commonly  gan- 
grenous, inflammation  are  present.     Erythrocytes  in  all  stages  of  necrosis 


Fig.  277. — Hkmiikkiiai.ic  Colitis.     (Oilon  of  a  dog;  colchicum  iMiisoninK  ot  twelve  hours'  duration.) — (Harris.) 
a.  Mucosa,    b.  Mu.-^ularis  mucosa-,    c.  Submucosa.    </.  .ind  r.  .\Iu.sclc  layers  of    the  intestine.    /.  Bloo<l  be- 
tween the  gl-ind  crypts,    g.  .Ahere<l  epithelium  of  cr>'i>t.    The  upper  leader  from  a  terminates  in  a  layer  of 
necrotic  mucoM.    The  blood  also  occupies  some  of  the  crypts,  the  epithelium  of  all  of  which  is  necrotic.    The 
submucosa  is  swollen. 


are  irregularly  scattered  through  the  affected  tissue.  At  points  the 
microscopic  hemorrhages  are  around  or  adjacent  to  capillaries,  in  some 
of  which  ruptures  may  be  discerned.  Usually  the  process  is  diflfuse, 
although  occasionally  it  is  singularly  punctate.  In  other  cases  the  diffuse 
and  punctate  forms  occur  together,  giving  rise  to  a  re<ldened  mucosa  in 
which  numerous  hemorrhages  may  be  observed.  In  exceptional  in- 
stances large  ecchymotic  spots  and  submucous  infiltration  by  blood  are 
coincident.  When  associated  with  catarrhal  or  pseudomembranous 
inflammations,  extending  necrosis  gives  rise  to  changes  indistinguishable 


e-6  SPECIAL  PATHOLOGY. 

from  those  seen  in  the  type  of  inflammation  commonly  called  gangrenous. 
It  is  possible,  although  not  probable,  that  when  small  areas  are  affected 
the  blood  may  be  removed  without  destruction  of  the  involved  mucosa. 

Hemorrhagic  inflammation  aft'ects  particularly  the  colon  (dysentery), 
pharynx,  mouth,  and  nasal  cavities;  occasionally  inflammations  of  the 
endometrium,  bladder,  urethra,  and  rectum  are  of  this  type.  In  toxic 
gastritis,   and   in   the   stomach   lesions   accompanying   some   infectious 


Pjc  278— Uterus  Case  of  Septic  Endometritis  with  Extensive  Necrosis  of  the  Entjometrium  and 
Myometrium,  due  to  Postpartum  Infection.  The  Organ  Has  Been  Laid  Open  by  Incision  through 
the  Anterior  Wall. 

A  Seal-  I  inch.  B,  B,  B.  Cavities  formed  bv  extensive  necrosis  C.  Necrotic  zone  that,  on  its  inner  surface, 
projects  as  a  shaggv  fragmenting  stratum  and  externally  is  bounded  by  D,  the  line  of  hyperemia  and  leu- 
kocytic accumulation.  (See  Fig.  279-)  £•  Muscle  layer  not  presenting  any  conspicuous  gross  lesion,  f. 
Peritoneal  surface;  early  stage  of  serofibrinous  inflammation  (the  block  of  tissue  from  which  the  microscopic 
drawnng,  Fig.  279,'was  prepared  was  taken  from  just  above  this  point).    G.  Thrombosed  sinus. 

diseases  (yellow  fever),  the  changes  in  the  gastric  mucosa  are  essentially 
hemorrhagic.  In  the  hemorrhagic  septicemias  of  man  and  lower  ani- 
mals the  lesions  occurring  in  the  mucosae  are  of  this  type.  The  condi- 
tion mav  readilv  be  produced  bv  toxic  doses  of  colchicum  (see  Fig.  277). 
Inflammations  Attended  by  Distinct  Necrosis  of  the  Mucous  Mem- 
brane.— In  some  cases  of    catarrhal    inflammation,   and  when  pseudo- 


M  U  CO  V  S   M  1-:  M  H  U  A  N  K S . 


557 


membrane  is  formed,  particularly  i 
necrosis  restricted  to  the  epithelial 
ditions  at  present  under  considera- 
tion differ  from  the  ])receding  in 
the  fact  that  tissue  death  extends 
deeper,  involving  the  basement 
membrane,  and  fretjuently  the  sub- 
mucosa.  Xo  little  confusion  exists 
as  to  the  name  which  should  be 
applied  to  the  group  of  processes 
in  which  this  change  is  observed. 
As  the  condition  is  commonly  a 
manifestation  of  diphtheria,  it  was 
at  one  time  known  as  diphtheritic 
inflammation.  This  term  was 
utilized  to  tiifferentiate  diphtheria 
from  croup,  the  prevailing  belief 
being  that  they  were  distinct  dis- 
eases. It  is  now  known  that  the 
Bacillus  diphtherias  may  cause 
both,  and  other  inflammations  as 
well,  and  that  the  disease  clinically 
and  bacteriologically  called  diph- 
theria may  be  manifested  by  pseu- 
do membrane  formation,  or  by 
necrotic  processes  extending 
deeper,  or  by  both.  In  order  to 
prevent  the  confusion  resulting 
from  the  term  tliphtheritic,  gan- 
grenous inflammation  has  been 
substituted.  The  latter  term,  how- 
ever, is  objectionable  because  gan- 
grene implies  the  death  of  larger 
masses  of  tissue  than  necessarily 
occurs  in  this  connection.  The 
i^augroioiis  sore  throat  and  iia)iQrcnc 
of  the  fauces,  also  called  i^a}i^re)ious 
anf^iiia, — these  terms  were  espe- 
cially used  by  the  older  writers, — 
are  forms  of  necrosing  inflamma- 
tion almost  invariably  due  to  the 
Klebs-Loffler  bacillus. 

Inflammation  of  the  mucosas 
attended  by  necrosis  may  follow 
burns,  scalds,  the  application  of 
escharotics.  and  trauma.  Embolic 
occlusion  of  the  nutrient  vessels 
to  an  area  of  the  mucous  mem- 
brane may  lead  to  death  of  the  in- 
volved structures.  In  practically 
all  the  conditions  manifested  by 
gangrenous   inflammation,  throm- 


n   the  latter  instance,  more  (;r  less 
layer  is  usually  present.      The  con- 


-;,  »>• 


<^'s    ISy 


I-'iG.  27g.— L'tkrus,  Skction  fkom  Spk(  imkn  Shown 
IN  Fic.  27S.  (Kixcd  in  Zenker's  lluid;  paraffin 
fosin,  toluidin  Mur.  Ul>j.  I.oiu  }ft  mm.,  oc. 
riimix-nsalion,  an<l  rcduccil  twn  ihinls.) 

.1.  Aliovc  this  [xiint  is  the  neirotic  hiyrr  consi.Ming  of 
Kranular  detritus  conl.iininK  enormous  numt<crs  of 
liacteria.fr.iRmenlinithistiil.i^'i,  ,  1, m, m.  ,11, 1  !■  iikiv 
rytes.      H.  From  .1   to  fl  1  :iiia, 

leukocytic  invasinn.  and  ir  lira- 

lion.      Vimi,  r..M,  HI,  rin.  ■•  ric» 

are  sh'  />'  to 

C'  mil-  iMrt 

..I   !\i.  !ual 

Aina 
iC 


linn, 
serou- 


'  red 


leukocytes  And  indutheli.il  cclU. 


5^8  SPECIAL   PATHOLOGY. 

bosis  of  the  capillaries  in  the  affected  area  occurs;  in  most  instances 
the  arrest  in  the  capillary  circulation  is  due  to  the  same  cause  as, 
and  is  part  of,  the  necrosis.  I  have,  on  two  occasions,  observed  a 
most  extensive  proctitis  follow  the  continuous  use  of  opium  and  mor- 
phin  in  patients  who  used  three  to  six  grams  of  the  latter  each  day 
by  rectal  suppositorv.  Administration  of  mercury,  antimony,  or  arsenic 
has  been  followed  bv  gangrenous  processes  involving  the  mucous  surfaces. 
It  is  probable  'that  cancrnni  oris,  noma,  or  gangrenous  stoniatiHs 
is  due  to  a  bacteritic  factor,  although  Lingard's  bacillus  is  not  gen- 
erally believed  to  be  the  cause. 
(See  Diseases  of  the  Alimentary 
Canal;  also  Gangrene,  p.  256.) 
This  disease  occurs  in  debilitated 
children,  and  usually  follows  one 
of  the  acute  infectious  diseases, 
most  commonly  (fifty  per  cent,  of 
the  cases)  measles. 

The  necrotic  processes  affecting 
the  mucosae  and  due  to  infection 
by  pyogenic  cocci,  or,  less  fre- 
quentlv,  the  pneumococcus,  occa- 
sionally manifest  a  clearly  gan- 
grenous tendency.  In  tissues  weak- 
ened by  any  associated  lesion,  and 
often  when  reduced  resistance  is 
not  demonstrable,  other  bacteria, 
as  the  colon  bacillus,  typhoid 
bacillus,  and  the  Bacillus  pneu- 
monise,  may  give  rise  to  gangren- 
ous processes. 

Morbid  Anatomy.  —  Whether 
the  initial  cause  be  infection  or 
not,  the  circulation  is  arrested  in 
the  area  involved,  and  coagulation 
necrosis  promptly  results;  infec- 
tion (primary,  secondary,  or  multi- 
ple), is  now  assured,  and  disintegra- 
tion follows.  In  other  cases,  the 
slough,  after  a  varying  period,  may 
be  detached  and  cast  off,  or  remain- 
ing in  position  it  is  decomposed  by 
bacteria;  in  other  words,  putrefies. 
As  the  necrotic  area  extends  into 
the  submucosatoa  varying  depth, 
the  lymphatic  system  is  widely 
opened  and  absorption  of  microbic  poisons  follows,  with  all  the 
phenomena  of  grave  septic  intoxication.  The  plugs  that  occlude 
the  vessels  become  infected  and  disintegrate,  and  hemorrhage  may 
result;  or  bacteria  (most  commonly  pyogenic  cocci)  gain  ingress 
to  the  lymphatic  system,  and  enlargement,  and  even  abscess  forma- 
tion, in  the  nearest  lymph-nodes  may  follow;  or,  bacteria  reaching 
the  blood  give  rise  to"  septicemia.     The  necrosis  may  assume  phage- 


•-'>'^>  ■--■/—''  ''^A-^f^^^-T'°^''~5^'^V^"«i^^^fe 


W' 


Fig.  280. — \"ertical  Section  of  Mucous  Membrane, 
Showing  Diphtheric  or  Gangrenous  Inflam- 
mation, FROM  a  Case  of  Dysentery. — {Schmaus.) 
X  40  diameters  (?). 

a,  b.  Muscular  layers,  c  Submucosa  with  widely 
distended  blood-vessels,  swelling,  and  leukocytic 
infiltration.  </.  .\dherent  portion  of  the  mucosa 
in  which  degenerative  and  necrotic  changes  are  in 
progress  and  which  fades  off  into  e,  the  necrotic 
layer  of  the  mucosa.  /.  Part  of  a  gland  in  the  ne- 
crotic tissue,  the  structure  of  the  gland  elements 
not  having  been,  as  yet,  destroyed,  although  sep- 
arating with  the  necrosed  layer,  g.  Distended 
blood-vessel. 


MUCorS   .M1:MH  RANKS.  ;;(; 

denic  characters,  followed  by  wide-spread  destruction ;  tliir,  in  pmli- 
ably  due  to  a  secondary  infection,  although,  of  course,  it  may  have 
been  primary,  and  is  typifieil  in  noma.  Kiin.urcnous  intlammation 
of  the  lal)ia  in  the  female,  and  of  the  glans  i)enis  in  the  male.  The 
initial  process  in  the  latter  cases  may  have  been  a  chancre  or  a  chan- 
croid. When  involvini,'  the  interior  of  the  uterus,  folhnving  labor  or 
abortion  (septic  endometritis),  the  mucosa  becomes  necrotic  and  the 
process  rapiiily  invades  ihc  myometrium,  in  the  sinuses  of  which  sej)- 
tic  thrombi  form.  The  resulting  septic  sinusitis  may  extend  to  the 
uterine  and  parauterine  veins  or  even  beyond,  producing  an  extending 
thrombosis,  which,  by  impeding  the  circulation  and  disseminating  bac- 
teria, furthers  the  progress  of  the  necrosis. 

This  form  of  inflammation  is  most  common  in  the  tonsils,  pharynx, 
mouth,  external  genital  organs,  rectum,  and  colon,  but  is  not  infre- 
quent on  other  membranes  as  well.  The  author  has  observed  a  severe 
gangrenous  cystitis  that  followed  prostatic  abscess  with  urinarv  infil- 
tration. 

Suppurative  and  pustular  inflammations  of  the  mucous  membranes 
are  sometimes  observed  m  pyemia,  septicemia,  smallpox,  and,  rarch  , 
in  other  infectious  febrile  processes.  Erysipelas  of  the  mucous  mem- 
brane may  be  followed  by  suppuration.  Diphtheria  may,  bv  render- 
ing mixed  infection  possible,  give  rise  to  pus  formation  in  the  sub- 
mucosa.  Pyogenic  infection  of  the  submucosa  results  from  abrasion  or 
destruction  of  the  protective  epithelium,  or  from  the  accumulation  of 
infective  material  in  a  mucous  gland  with  obstructed  duct ;  the  base- 
ment membrane  of  the  gland,  being  less  resistant  than  the  overlving 
tissues,  distends  and  ruptures  into  the  submucosa,  leading  to  infection 
and  pus-formation  in  the  affected  tissues.  This  is  probably  the  process 
giving  rise  to  suppurative  tonsillitis  and  allied  conditions. 

In  some  cases  of  mucous  membrane  inflammation  the  exudate  is 
composed  largely  of  polymorphonuclear  leukocytes  and  the  condition 
is  due  to  organisms  of  fully  established  pyogenic  pro])erties.  This  tvpe 
of  mucous  membrane  intlammation  is  commonly  produced  by  the 
gonococcus,  in  which  case  the  process  is  callcil  gonorrhea.'  When  due 
to  other  pyogenic  organisms  it  is  known  as  suppurative  catarrh.  Catar- 
rhal inflammations  characterized  liy  purulent  or  mucopurulent  dis- 
charges attack  particularly  the  urethra  and  birth  canal,  but  may  also 
involve  the  mucosa  of  the  nose  and  bronchi,  the  conjunctiva,  an<l 
middle  ear.  An  essentially  similar  condition  affects  the  Fallopian 
tube  (suppurative  salpingitis)  and,  as  a  result  of  occlusion  of  the  two 
ends  of  the  tube,  the  i)us  accumulates  in  the  resulting  cavity  (pyosal- 
pinz).  In  some  of  these  conditions  the  pyogenic  organisms  cnttT 
the  submucosa  in  sutTuient  numbers  to  induce  suppuration.  In  this 
way  periurethral  abscess  complicating  gonorrhea,  and  the  cellulitis  in- 
volving the  pharynx  and  the  areolar  tissues  of  the  floor  of  the  mouth 
(Ludwig's  angina),  are  produced.  In  some  cases  the  infiltration  is 
rather  diffuse,  the  polymorphonuclear  leukocytes  being  distributed  in 
the  lymph-spaces  and  not  aggregated  to  form  abscesses.  Suppurative 
interstitial  gastritis  may  be  mentioned  as  a  type  of  this  form  of  sub- 
mucous infection.  In  many  cases  the  bacteria  penetrate  the  submucosa 
from  the  surface,  but  it  is  also  possible  for  the  same  result  to  follow 
hematogenous  infection. 

'  See  p.  107 


i^6o  SPECIAL   rATHOLOGY. 

Sui)i)urative  processes  are  usually  situated  in  localities  liable  to 
injury  and  accompanying  infection,  or  in  membranes  rich  in  sulci 
affording  lodgment  for  substances  containing  bacteria  that  subsequently 
give  rise  to  mfection;  aside  from  the  specific  diseases,  such  as  small- 
pox, in  which  the  suppuration  occurs  in  the  form  of  pustules  in  the 
mouth  and  adjacent  membranes,  the  most  common  sites  of  the  process 
have  been  indicated.  In  the  appendix  the  infection  and  pus-formation 
in  the  submucosa  mav  find  less  resistance  to  egress  toward  the  peritoneum 
than  toward  the  mucous  tract,  and  hence  appendicitis  not  uncommonly 
gives  rise  to  infection  of  the  serosa.  In  similar  obstructive  condi- 
tions affecting  the  Fallopian  tubes,  rupture  into  the  peritoneum  may 
afford  a  more  favorable  route  for  the  infection  and  emptying  of  the 
distended  tube  than  escape  into  the  uterine  cavity.  While  the  fore- 
going reference  to  appendicular  and  Fallopian  disease  is  made  under 

Suppurative  Inflammation,  it  is 
not  to  be  forgotten  that  accumu- 
lated catarrhal  material  contains 
abundant  infectious  agents,  and 
that  its  escape  will  as  certainly 
be  followed  by  septic  inflammation 
as  though  an  abscess  had  poured 
its  contents  into  the  serous  cavity. 
Suppurative  and  gangrenous  pro- 
cesses are  not  uncommon  in  the 
appendix,  and  it  does  not  seem 
probable  that  the  Fallopian  tube, 
once  infected,  would  be  less  liable 
to  the  same  processes. 

Chronic  infectious  inflamma- 
tions of  the  mucous  membranes 
are  of  the  greatest  importance,  and 
deserve  the  closest  study.  For  the 
most  part  they,  from  the  begin- 
ning, involve  the  essential  function 
of  the  mvicous  surface  by  invading 
the  submucosa.  Included  under 
this  head  are  tuberculosis,  leprosy, 
syphilis,  glanders,  actinomycosis, 
and  rhinoscleroma. 
Tuberculosis  of  the  mucous  membranes,  independent  of  pulmonary 
tuberculosis,  is  not  a  rare  condition.  In  the  upper  air-passages  it  is 
a  most  frequent  occurrence  in  tuberculous  patients,  arising  in  the  larynx, 
in  the  bronchi,  and  occasionally  in  the  nose.  Tuberculosis  of  the  ali- 
mentary canal  has  been  noted  in  every  structure  from  the  lips  to  the 
anus.  The  cause  is  the  bacillus  of  tuberculosis,  which  has  been  con- 
sidered in  the  section  on  Bacteriology.     (See  Tuberculosis,  p.   144.) 

Morbid  Anatomy. — The  infection  may  be  from  the  surface  or  by 
the  blood  or  lymph.  Commonly  the  entrance  of  tubercle  bacilli  into 
the  submucosa  is  promptly  followed  by  the  development  of  mihary 
tubercles,  usually  around  or  near  a  blood-vessel.  In  marked  cases  of 
general  miliarv  tuberculosis  the  tubercles  can  be  seen  at  many  points 
in   the   mucous   membrane.     A   little  later  these   bodies   coalesce   and. 


Fig.  281. — Intestine,  Chronic  Secondary  Tuber- 
culosis; Irregular  Ulcers  the  Floors  of 
WHICH  Present  a  Necrotic  Surface.  The 
Ulcers  are  Transverse  to  the  .\xis  of  the 
Bowel. 


MUCOUS   MEMBKANKS.  561 

by  obliterative  changes  induced  in  the  blood-vessels,  deprive  the 
basement  membrane  and  overlying  epithelium  of  their  proper  nutrition: 
by  this  time,  through  confluence,  necrosis,  and  softening,  a  cheesy 
area  develops,  and,  breaking  through  the  basement  membrane  the 
caseous  material  is  discharged  and  an  ulcer  results.  The  long  axis  of 
the  ulcer  is  usually  transverse  to  the  long  axis  of  the  membranous 
tube — a  condition  due  to  the  usual  circumferential  distribution  of  the 
blood-  and  lymph-vessels.  External  to  the  area  of  ulceration  new 
fibrous  tissue  develops  and  contracts,  in  many  localities  giving  rise  to 
stenoses.  When  examined  in  its  earlier  stages,  the  condition  is  known 
as  miliary  tuberculosis;  and  later,  when  ulceration  has  ensued,  or  in 
the  stage  of  caseation,  as  ulcerative  or  caseous  tul)crculosis,  respectively. 


/ 


FlC.    282. — ^MAKGIN  op   TuBERtXLOOS    LLti-K   ur    THt    i.SrtMI.Nt. 

Specimen  h.ordened  in  corrosive  sublimate,  infiltrated  with  paraffin,  stained  with  hcrn,i!"xvlin  and  eo«in.  snH 
mounted  in  balsam,    j.    Mucosa  that,  as  it  approjiches  the  ulcer,  is  swollen  and  llii  ' 
anddesrjuamatinj;  cells.     b,d,  and  e.   Tuberclts  situated  in  thesubmucosa;  b  andu 
and  lo  ihe  right  of  d,  each  show  a  central  gi.ant  ("<1|.      The  tubercle  e  shows  ccntr.il 

caseation.  Note  the  extensive  inliltration  of  the  submucosa  with  small  lymphoid  ri  11^  «mic[i,  mum  n  uny 
undrr  the  ulcer,  at  /,  have  invaded  the  circular  musclc-tibcrs.  c.  The  longitudinal  muscular  layer,  which,  at  j, 
contains  a  s<ilitary  tubercle,     ("i-inch  objective;   i-inch  ocular.) 

Rarely,  calcareous  changes  may  occur  and,  as  a  result  of  infiltration 
with  lime  salts,  the  tubercle  becomes  quiescent,  and  the  process  is  ar- 
rested. Occasionally  in  the  mucous  membrane  of  the  intestine,  partic- 
ularly in  the  ileocecal  area,  and  rarely  in  other  mucosae,  the  affection 
is  characterized  by  the  production  of  a  large  amount  of  fibrous  tissue 
and  great  thickening  of  the  submucosa,  constituting  what  is  called 
chronic  hyperplastic  tuberculosis.'  The  anatomy  of  tubercles,  their 
method  of  infection,  etc.,  have  been  considered  with  tuberctilosi^-  in 
general. 

'  See  r.  153. 

'  Sec  Morbid  Anatomy  of  Tuberculosis,  p.  149;  also  tuberculosis  of  the  various 
iTiucosap,  alimentarv-  canal,  organs  of  respiration,  urioar>'  organs,  etc. 

37 


562  SPECIAL  PATHOLOGY. 

Leprosy^  of  the  Mucous  Membranes. — In  purely  anesthetic  leprosy 
the  only  involvement  noted  by  observers  is  in  the  colon,  where  ulcers 
are  said  to  develop  without  leprous  tubercles.  Tubercular  leprosy  is 
prone  to  attack  the  mucous  membranes,  especially  the  conjunctiva, 
cornea,  larynx,  and  nose.  The  leprous  tubercles,  like  those  of  tuber- 
culosis, occur  around  the  blood-vessels  in  the  submucosa;  as  the  pro- 
cess extends,  the  blood-supply  is  cut  off  by  the  obliterative  changes 
in  the  vessels,  and  a  fibroid  area  results.  Ulceration  is  not  inevit- 
able, or  even  frequent,  as  in  tuberculosis.  Sometimes,  however,  the 
leprous  infiltration  is  followed  by  pyogenic  infection,  softening,  and 
ulceration.  The  disease  is  due  to  the  Bacillus  leprae,  which  has  been 
considered  when  dealing  with  bacteria. 

Syphilis-  of  the  Mucous  Membranes. — In  primary  syphilis  the  lesion 
is  far  more  frequent  in  the  mucous  membrane  than  in  the  skin.  The 
submucosa  becomes  infiltrated  with  small  round  cells,  in  which  epithelioid 
and  giant  cells  may  be  found;  the  blood-supply  to  the  surface  is  cut  off 
by  obliterative  changes  in  the  arteries,  and  ulceration,  or  rather  coagu- 
lation necrosis,  ensues.  The  roseolar  rashes  of  the  secondary  stage 
leave  no  discernible  lesion.  The  mucous  patches  and  ulcers  are  the 
result  of  coagulation  or  liquefaction  necrosis,  and  occur  in  the  mucosa 
of  the  tongue,  pharynx,  tonsils,  palate,  gums,  and  cheeks,  and  also  on  the 
mucous  membrane  of  the  anus  and  genital  organs. 

The  lesion  of  tertiary  syphilis  affecting  the  mucous  membranes  is  the 
gumma,  which  occurs  in  the  submucosa,  develops  like  the  previously  con- 
sidered infective  granulomata,  and,  when  untreated,  usually  undergoes 
necrosis  and  ulcerates.  As  the  ulcer  heals,  contracting  cicatrices  give 
rise  to  strictures;  these  are  most  frequent  in  the  larynx,  rectum,  and 
esophagus.  (See  illustrations  of  syphilitic  stenosis  of  the  larynx  and 
trachea,  Fig.  286,  p.  573.)  Should  cicatrization  occur,  without  ulcer- 
ation, contraction  is  equally  sure  to  follow,  but  is  less  obstinate. 

Glanders^  of  the  Mucous  Membranes. — This  disease,  due  to  the  Bacil- 
lus mallei,  manifests  itself  usually  in  the  nose  as  ulcers  brought  about  by 
the  development  of  glanders  nodules,  made  up  of  lymphoid  and  epithe- 
lioid cells  in  the  submucosa,  which,  by  necrosis,  give  rise  to  an  ulcer. 
In  the  acute  form  gangrenous  and  septic  phenomena  not  uncommonly 
accompany  the  process ;  in  the  chronic  form  the  ulcers  may  be  mistaken 
for  those  due  to  protracted  catarrhal,  tuberculous,  or  syphilitic  disease. 
Demonstration  of  the  bacillus  is  essential  to  an  accurate  diagnosis. 

Actinomycosis'*  of  the  mucous  membranes  is  most  common  in  the 
tissues  about  the  mouth  and  in  the  alimentary  canal,  especially  the  ileo- 
cecal area,  but  may  affect  other  mucosas.  The  ray  fungus,  like  other 
chronic  infections,  gives  rise  to  a  collection  of  granulation  tissue  in  the 
submucosa.  The  infiltration  may  be  indurative  with  but  little  tendency 
toward  necrosis;  in  other  cases  softening  and  suppuration  are  followed 
bv  necrosis  of  the  overlying  mucous  membrane,  producing  an  ulcer.  The 
diagnosis  is  made  by  the  demonstration  of  the  fungus  in  the  discharges 

'See  Bacillus  leprae,  p.  157;  also  forms  and  manifestations  of  leprosy,  pp. 
158  and   159. 

^  See  Syphilis,  p.  174;  Histology  of  Chancre,  p.  177;  Mucous  Patch  and  Gum- 
ma, pp.   179  and  180. 

^  See  Glanders,  pp.   160  to  162. 

*  See  Actinomycosis,  p.  166;  also  Paths  of  Infection  in  Morbid  Anatomy  of 
Actinomycosis,  p.  168. 


MUCOUS   MKMBRANES.  563 

or  in  sections  of  the  infected  tissue.  The  new  formation  is  usually 
surrounded  by  a  zone  of  j)roliferating  connective  tissue,  which,  in  the 
jaw,  has  hicii  niisLaken  for  sarcoma.     Sooner  or  later  suppuration  ensues. 

Rhinoscleroma'  consists  in  the  thickening  and  tumefaction  of  the 
submucosa  of  the  nose,  rarely  extending  to  the  pharynx  or  larynx;  the 
affection  usually  begins  in  the  nose.  The  indurated  areas  are  at  first 
red  or  pink,  and  are  very  tender;  later  they  become  white.  The  disease 
is  alleged  to  be  due  to  a  bacillus  found  in  the  tumefied  tissues,  usually 
in  the  hyaline  cells  of  the  tibrous  meshwork.  Rhinoscleroma  is  rare  in 
this  country,  and  clinically  resembles  lupus.  It  is  e.ssentially  chronic  as 
to  time,  requiring  years  to  develop  fully. 

Thrush-  is  a  disease  largely  restricted  to  the  mucous  membranes, 
usually  atlccting  the  mouth,  in  which  location  the  condition  is  called 
mycotic  stomatitis.  The  mucosa  of  the  esophagus  is  sometimes  involved, 
and  other  parts  of  the  alimentary  canal  less  frequentlv. 

The  tumors  which  may  occur  on  or  in  mucous  membranes  are  nu- 
merous, and,  as  certain  localities  seem  liable  to  special  varieties,  it  is 
thought  best  to  record  the  neoplasms  and  cysts  with  the  special  path- 
ology of  each  region. 

'  Sec    Rhinoscleroma,   p.    150. 
^  See  p.    165. 


CHAPTER  VIII. 
ORGANS  OF  RESPIRATION. 

Anatomic  Divisions. — The  anatomist  divides  the  organs  of  respira- 
tion into  the  nose  or  nasal  cavities,  larynx,  trachea,  bronchi,  and  lungs. 
For  physiologic  consideration  it  is  important  to  recognize  a  conducting 
part,  including  all  but  the  lungs,  in  which  the  essential  chemistry  and 
vital  phenomena  of  respiration  occur.  Incidentally,  other  functions 
are  performed  by  the  various  parts  of  the  whole,  one  function  being 
accessory  to  another, — e.  g.,  olfaction  in  the  nose,  vocalization,  etc., 
in  the  larynx, — all  aided  by  and  dependent  upon  the  various  muscular 
and  bony  structures  of  the  chest  with  its  complex  innervation. 

NOSE. 

Malformations.— The  nose  may  be  absent  or  may  be  represented 
by  a  teat  or  a  snout-like  projection  in  cyclopia  or  synophthalmia — a  mal- 
formation attended  by  a  single  orbital  cavity,  centrally  located,  and 
containing  one  or  two  eyeballs  in  varying  stages  of  development;  rarely, 
the  eye  is  absent.  Other  malformations  of  the  nose  consist  in  absence 
of  one  or  more  muscles,  clefts  of  the  alae,  deviations  and  faulty  de- 
velopment of  the  septum,  incomplete  development  of  some  of  the 
bones  entering  into  the  formation  of  the  cavity,  constriction  of  the 
nares,  more  or  less  complete,  and  clefts  in  the  floor  of  the  nasal  cavity, 
usually  associated  with  faulty  development  of  the  lip,  palate,  or  other 
soft  parts.  According  to  Boulay,^  there  are  80  recorded  cases  of  con- 
genital occlusion  of  the  nares.  The  occlusion  was  unilateral  in  39  of 
65  fully  reported  instances;  in  51  it  was  osseous,  partly  osseous  in  7, 
and  membranous  in  7.  The  deviation  of  the  nasal  septum  (scoliosis 
septi")  may  be  unilateral,  bilateral,  zigzag  or  irregular;  the  inclination 
may  be  (i)  toward  one  side  (simple  deviation),  (2)  vertical  sigmoid, 
one  or  more  convexities  directed  toward  each  fossa,  or  (3)  antero- 
posterior sigmoid. 

Hemorrhage  from  the  nose  (epistaxis)  occurs  as  the  result  of  injury, 
either  directly  applied  to  the  nasal  structures,  or  falls  and  blows  severely 
jarring  the  head,  and  in  fractures  involving  the  base  of  the  skull. 
Extreme  plethora  is  asserted  to  be  a  cause ;  bleeding  from  the  nose  may 
be  produced  by  hyperemia,  either  premonitory  to  inflammation  or 
secondary  to  overexertion  and  forcible  cardiac  action;  violent  respiratory 
acts,  like  strangling,  coughing,  or  sneezing;  intracranial  congestion  and 
hyperemia ;  the  passive  congestions  of  heart  disease  and  obstructed  return 
of  blood  from  the  head,  as  in  tumors  pressing  on  the  veins  of  the  neck ; 
occasionally  the  hemorrhage  is  vicarious,  as  in  arrested  menstruation  and 
suspended  excretion  (e.  g.,  sweating  and  suppression  of  urine);    severe 

^  "Arch,  de  M6d.  des  Enfants,"  March,  1902. 

^  Sheedy,  "The  Postgraduate,"  Oct.,  1902,  p.  1130. 

564 


ORGANS   OF   KKSIMRATION'.  565 

vomiting;  tumors,  ulcerations,  etc.,  of  the  nasal  mucosa;  bUjod  diseases, 
like  hemophilia,  scurvy,  leukemia,  etc.  Epistaxis  is  also  seen  in  the  early 
stages  of  some  of  the  acute  infectious  diseases,  most  commonly  typhoid 
fever.  Renal  disease,  associated  with  a  rise  in  blood -pressure,  and  cir- 
rhosis of  the  liver  are  also  causes.  Martinet'  lays  particular  stress  upon 
the  occurrence  of  epistaxis  in  arteriosclerosis  and  believes  that  the  con- 
dition is  due  to  the  associated  hypertension.  Osler^  has  described  a 
fonn  of  epistaxis  due  to  multiple  telangiectases  of  the  nasal  mucosa. 
In  some  cases  the  hemorrhage  appears  to  come  from  the  ethmoidal 
veins  and  possibly  from  other  sinuses.^  Death  from  epistaxis  is  rare. 
The  quantity  of  blood  lost  varies,  but  usually  stops  short  of  danger. 
When  bleeding  is  repeated,  there  is  not  infrequently  some  local  lesion 
to  account  for  it,  such  as  erosion  or  ulceration,  usually  situated  on  the 
septum.  Varicosity  of  the  veins  of  the  nasal  mucosa  may  sometimes 
be  recognized. 

Infiammation  ^  of  the  nasal  mucosa  is  called  rhinitis.  Any  of  the 
already  tiescribcd  mucous  membrane  inflammations  may  occur  in  the 
nose.  Acute  catarrhal  rhinitis,  acute  nasal  catarrh,  or  coryza  is  the 
most  frequent  of  the  intiammations  affecting  the  nasal  mucosa.  Of 
the  many  conditions  believed  to  be  operative  in  the  production  of  acute 
catarrhal  rhinitis,  infection  is  most  important.  Cold  and  exposure, 
irritants,  such  as  ammonia,  and  superheated  gases  are  said  to  be  etiologic 
factors.  Cold  and  exposure  are  probably  of  secondary  importance, 
and  act  by  increasing  the  susceptibility  of  the  membrane  to  infection. 
There  is,  at  times,  evidence  indicating  that  the  condition  is  contagious. 
The  inflammatory  process  secondary  to  infectious  diseases,  such  as  in- 
fluenza and  typhoid  fever,  should  be  mentioned. 

Fibrinous  and  gangrenous  inflanimations  of  the  nose  may  be  primary, 
but  are  more  frequently  associated  with  or  secondary  to  a  primary 
pharyngeal  lesion.  Pseudomembranous  rhinitis  is,  in  a  certain  per- 
centage of  cases,  a  nasal  manifestation  of  diphtheria.'"  This  statement 
applies  not  only  to  the  acute  forms,  but  to  the  more  chronic  cases  as 
well.  Some  of  the  latter  show  a  persistent,  rather  long-continued 
pseudomembranous  inflammation;  the  diphtheria  bacillus  is  present  in 
the  exudate,  and,  in  rare  instances,  has  constituted  the  starting-point 
for  an  epidemic  of  dijihtheria.  Pneumococci,  streptococci,  staphylo- 
cocci, Friedlander's  bacillus,  and  other  organisms  occasionally  produce 
a  false  membrane  in  the  nose.  Pseudomembranous  rhinitis  from  other 
causes  occurs,  but  is  infrequent.  Chronic  catarrhal  rhinitis,  also  called 
chronic  nasal  catarrh,  usually  follows  repeated  severe  attacks  of  acute 
inflammation,  although  occasionally  it  comes  on  insidiously  and  may 
induce  lesions  of  considerable  magnitude  before  symptoms  appear.  In- 
halation of  irritants  and  dust  and  the  presence  of  foreign  bodies  are  also 
causes.  Various  constitutional  vices — such  as  chronic  heart  disease, 
tuberculosis,  syphilis,  anemia,  etc. — are  also  important  causes.  The 
extreme  aridity  of  houses  heated  by  modern  methods  undoubtedly  pre- 

'  "  La  Presse  Med,"  April  6,  1904. 

'"Bull.  Johns  Hopkin-s  Hospital,"  Nov..  looi,  p.  ^?^  Reference  to  pre- 
vious reports. 

'Kelly,  "Lancet."  Feb.  24,  iqoo. 

*  For  pathology'  of  inflammations  of  the  mucous  membranes  see  p.  546. 

*  For  references  to  literature  on  nasal  diphtheria  consult  article  by  Wilner, 
"  N.  Y.  Med  Jour.,"  Nov.  5.   IQ04,  p.  SSi. 


566  SPECIAL  PATHOLOG.Y. 

disposes  to  catarrh.  The  presence  of  tumors,  particularly  of  polypi, 
is  said  to  favor  the  condition,  or  may  be  an  important  determining 
cause ;  in  other  cases  overgrowth  of  the  mucous  membrane  may  assume  a 
polypoid  character,  a  fact  supporting  the  view  that  the  inflammation 
leads  to  tumor  formation.  The  inflammatory  processes  may  be  hyper- 
trophic or  atrophic,  and  may  or  may  not  be  associated  with  fetid  discharge 
(ozena).  There  is  a  form  of  nasal  inflammation  that  has  received  the 
name  purulent  rhinitis,  by  reason  of  the  pus-like  character  of  the  dis- 
charge ;  an  inflammation  of  this  kind  not  infrequently  follows  the  presence 
of  foreign  bodies,  nasal  tumors,  suppurative  processes  in  accessory 
sinuses,  acute  infection,  such  as  gonorrhea,  and  the  ulcerative  stages  of 
the  chronic  infections,  particularly  glanders,  tuberculosis,  and  syphilis. 
Under  the  name  of  caseous  or  scrofulous  rhinitis  ^  has  been  described  a 
chronic  process  indicated  by  the  production  of  caseous  material  which 
often  accumulates  in  the  affected  nasal  fossa ;  the  condition  is  probably 
not  a  manifestation  of  tuberculosis  except  in  rare  cases;  a  leptothrix 
has  been  found  in  the  material,  and  it  is  possible  that  the  affection  is  a 
form  of  pseudo-tuberculosis.^ 

Tuberculosis  of  the  nasal  mucosa  may  be  primary  or  secondary. 
Renshaw'  collected  ii6  cases  of  tuberculous  rhinitis,  30  of  which  were 
primary.  In  the  former  group  ulceration  was  conspicuous,  and  in  the 
latter,  the  polypoid  form  was  most  frequent.  Syphilis  is  frequently 
the  cause  of  nasal  catarrh  and  may  give  rise  to  ulcerative  processes; 
gummata  of  the  tissues  forming  the  facial  nose  are  not  infrequent. 
Glanders  is  often  primary  in  the  nose.  Leprosy  and  actinomycosis 
sometimes  attack  the  nasal  mucosa  or  contiguous  tissues.  Rhino- 
scleroma  nearly  always  begins  in  the  nose. 

The  nasal  mucosa  being  continuous  with  that  of  the  sinuses  of  the 
superior  maxilla,  the  frontal  and  ethmoid  bones,  and  by  the  Eustachian 
tube  with  the  middle  ear,  inflammation  once  established  in  the  nose  may 
extend  to  these  structures,  where,  by  reason  of  faulty  drainage,  and 
inaccessibility,  chronic  processes  ensue.  The  sinuses  lying  in  prox- 
imity to  the  brain  may  afford  means  for  intracranial  infection,  as  seen 
in  middle-ear  disease  leading  to  cerebral  abscess,  and  in  the  tuberculous 
meningitis  asserted  to  follow  tuberculosis  of  the  nasal  cavities  and  their 
appendages.* 

Tumors. — Adult  Epithelial. — Adenomata  of  the  nasal  mucous  mem- 
brane occur  more  commonly  as  the  pharynx  is  approached,  but,  on 
the  whole,  are  not  frequent;  they  are  mostly  cystic,  owing  to  in- 
clusion of  a  mucous  gland,  ordinarily  by  inflammatory  tissue.  Papillo- 
mata  or  warts  are  usually  situated  in  the  vestibule ;  in  children  they 
are  frequently  of  syphilitic  origin.  A  hairy  papilloma  resting  on  a  base 
of  fat  (lipomatous  tissue)  has  been  described.  It  is  believed  to  be  con- 
genital (Arnold).  Carcinoma  of  the  nose  is  rarely  primary,  usually 
extending  to  the  nasal  cavity  from  the  mouth  or  face;  it  is  generally 
of  the  epitheliomatous  type  rather  than  glandular.  Schmidt  found 
five  carcinomata  of  the  nose  and  throat  in  32,997  patients.     Fibromata, 

1  Bark,  "Jour,  of  Laryngology,  Rliinology  and  Otolog3^ "  Dec,  1903. 

^  See  foot-note  p.   156. 

^  "Jour,   of   Path,   and   Bact.,"   Feb.,    1901. 

*■  For  literature  on  diseases  of  the  accessory  sinuses  of  the  nose,  see  Howard 
and  Ingersoll,  "Amer.  Jour,  of  Med.  Sci.,"  May,  1898;  also  Kirkland,  "Austral- 
asian Med.  Gazette,"  1902,  vol.  xxi,  p.  299. 


ORGANS   Ol-    KKSPIKATIO.N.  5^7 

choiuironuita,  ostconuita,  and  ))iyxonuitu  occur.  True  myxoma  is  rare, 
but  fibroniyxonia  arnl  pure  fibroma  are  of  not  infrequent  occurrence; 
some  nasal  polypi  belong  to  one  of  the  two  varieties.  Wright'  main- 
tains that  nasal  polypi  are  not  myxomatous  but  result  from  serous 
infiltration  of  the  submucosa  and  hyperplasia  of  the  superficial  layers. 
SartO))iata  occur  in  the  nasal  cavity,  arising  from  the  fibrous  tissue  of 
the  submucosa,  the  periosteum,  or,  rarely,  the  bone;  they  occasionally 
develop  in  the  sinuses:  c.  ^.,  the  antrum  of  Highmore. 

Erectile  tumors  (telangiectatic  polypi)  are  made  up  of  numerous 
thin-walled  blood-vessels  emlieddcd  m  a  fibrous,  mucoid,  or  adeno- 
matous matrix  containing  more  or  less  myxomatous  tissue.  They  are 
infrequent. 

Postnasal  Adenoids.- — There  must  be  some  doubt  as  to  the  advis- 
ability of  regardmg  these  enlargements  as  true  tumors,  and,  as  the 
new  growth  is  most  frequently  tlie  result  of  an  increase  in  pre-existing 
lymphoid  tissue,  the  term  postnasal  adenoid  hypertrophy  has  been 
applied.  The  disease  is  one  of  infancy  and  childhood,  most  frequent 
in  tuberculous  families,  and  is  commonly  associated  with  some  form  of 
rhinitis,  with  defects  of  development  in  the  osseous  walls  causing  stenosis, 
and  with  concomitant  pharyngeal  or  postnasal  catarrh.  The  growth 
is  most  marked  on  the  posterior  rhinopharyngeal  wall.  The  masses 
are  usuallv  sessile,  with  uneven,  granular,  or  lobulated  surfaces. 

Histologically,  the  growths  are  composed  of  hyperplastic  lymphoid 
tissue  in  which  the  quantity  and  density  of  the  reticulum  vary.  The 
fibrous  tissue  is  mostly  perivascular.  The  epithelium  covering  the 
mass  may  be  squamous  or  columnar;  the  latter  is  sometimes,  although 
rarely,  ciliated;  a  basement  membrane  can  usually  be  detected.  The 
epithelium  and  sometimes  the  deeper  tissue  is  necrotic.  The  crypts 
are  often  deeper  than  normal  and  are  not  infrequently  filled  with  caseous 
material.  So  far  as  the  growth  itself  is  concerned,  it  usually  atrophies 
and  disappears  at  or  about  puberty.  In  the  mean  time,  however,  the 
mechanical  interference  with  respiration,  and  the  associated  catarrh, 
induce  a  drain  on  the  patient's  general  health,  embarrass  respiration, 
and  may  be  accompanied  by  tuberculous  infection.  Dieulafoy  found 
tubercle  bacilli  in  twenty  per  cent,  of  the  adenoids  examined;  of  the 
seventy-five  studied  by  Lartigau  and  Xicol,  eight  contained  tubercles 
and  bacilli,  and  four  bacilli  without  tubercles.  Involvement  of  the 
Eustachian  tube  and  an  infective  otitis  media,  with  consequent  deaf- 
ness, are  not  infrequent  complications. 

Rhinoliths  are  calcareous  masses  occasionally  found  in  the  nose; 
they  arise  from  the  deposit  of  lime  salts  around  a  nucleus,  usually  a 
foreign  bodv.  or.  rarely,  from  inspissated  secretion.  Of  125  cases  col- 
lected by  Hall,'  the  largest  concretion  weighed  a  little  over  45  grams. 

Anosmia,  or  loss  of  the  sense  of  smell,  may  be  caused  by  (i)  cen- 
tral lesions  or  (2)  chronic  catarrhal  thickening,  and  contraction  may 

'  "N.  Y.  Med.  Record,"  Jan.  26.  iqoi.  See  al.so  Yonpc.  "Brit.  Med.  Jour.," 
Nov.   5.   1904,  p.    123Q. 

'  Lartigau  and  Nicol,  ".Xmer.  Jour,  of  Mod  Sti,  '  June,  1002;  Marsh,  Lan- 
cet," June  7,  1902.  Courtade,  "Archives  intemationales  de  ]ar\-nRolojfie,  d'oto- 
logie  et  de  rhinologie,"  Mars-.-Kvril,  \qo\.  Simpson.  "Adenoid  Growths  of  the 
Naso- Pharynx,"  1904.  Harris.  ".Vmcr.  Med.,"  Jan.  2.  1004,  p.  20.  Holz.  '  BerL 
klin.    Woch."    Jan.    23,    190s. 

'  "Trans,  of  Clin.  Soc.  of  London."  vol.  26.  p.  60.. 


^68  SPECIAL  PATHOLOGY. 

pinch  the  filaments  of  the  nerve,  and  thereby  destroy  them;  a  smiilar 
result  may  follow  periosteal  thickening,  as  seen  in  syphilis.  When 
the  sense  is  not  destroyed,  but  perverted,  the  term  parosmia  is  used. 
Hyperesthesia  of  the  olfactory  nerves,  also  called  hyperosmia,  is  usually 
dependent  upon  central  lesions  or  is  a  part  of  some  neurosis.  Exclu- 
sive of  the  abundant  exudate  seen  in  inflammations,  and  independent 
of  any  recognizable  change  in  the  membrane  of  the  nasal  cavity  and 
accessory  sinuses,  there  is,  at  times,  a  most  marked  serous  discharge, 
constituting  a  true  rhinorrhea.  The  cause  of  the  condition  is  not 
known.  The  case  reported  by  Glynn^  manifested  symptoms  simulating 
an  intracranial  tumor,  but  entirely  recovered  after  a  profuse  discharge 
from  the  nose  of  a  liquid  believed  to  have  been  cerebrospinal  fluid. 
The  reporter  was  of  the  opinion  that  an  internal  hydrocephalus  had 
drained  through  the  perineural  sheaths  of  the  olfactory  nerves.  Thomp- 
son maintains  that  spontaneous  rhinorrhea  of  cerebrospinal  fluid  is 
always  the  result  of  internal  hydrocephalus. 

LARYNX  AND  TRACHEA. 

Normal  Structure. — The  epithelial  layers  of  the  mucosa  vary  as 
to  depth  and  variety  of  epithelium;  the  epiglottis  and  the  true  cords 
are  covered  by  squamous  epithelium,  lines  of  which  extend  between 
the  epiglottis  and  cords.  The  greater  area  is  covered  by  ciliated  epi- 
thelium. 

Malformations. — Absence  of  the  larynx  is  rare.  Occasionally,  it  is 
small  and  poorly  developed  (hypoplastic),  a  condition  said  to  attend 
testicular  hypoplasia  and  to  follow  castration.  Abnormal  largeness  is 
at  times  noted.  Combinations  of  the  last-named  conditions,  giving 
rise  to  asymmetry,  are  more  frequent.  The  ventricles  may  be  abnor- 
mally large,  or  aberrant  sinuses  or  pouches  may  extend  into  the  peri- 
laryngeal tissues,  giving  rise  to  a  condition  known  as  emphysema  of 
the  neck,  or  aerocele.  From  faulty  union  of  the  branchial  arches  fis- 
tulas may  result.  Clefts  and  fissures  of  the  epiglottis  occur.  Defects  in 
the  laryngeal  cartilages  are  sometimes  observed,  but  are  rare.  FranckeP 
reports  two  instances  of  membranous  diaphragm  in  the  larynx;  similar 
cases  are  recorded  by  Harmer^  and  Fein^;  the  latter  collected  1 1  reported 
cases.  Simmonds^  describes  various  forms  of  flattening  and  distortion 
of  the  trachea  occurring  in  the  aged.  He  has  collected  sixty-one  cases; 
fifty-eight  of  the  patients  were  males.  All  were  over  fifty  years  of  age. 
In  some  cases  the  trachea  is  irregularly  dilated ;  the  ectasia  results  from 
yielding  of  the  elastica. 

Hemorrhage^  from  the  larynx  accompanies  injury,  severe  inflam- 
mations, tubercle,  and  tumors, 'particularly  the  highly  vascular  papillo- 
mata  and  carcinomata;  it  rarely  occurs  from  vascular  distention  and 
vicarious  function.  Hemorrhages  into  the  submucosa,  and  even  on 
the   free   surface,   are   sometimes   present  in   scurvy,   leukemia,   perni- 

*  "Med.  Soc.  of  London,"  Feb.  13,  1905. 
2  "Deut.  med.  Woch.,"  Dec.  iS,  1902. 
3"Wien.   klin.    Woch.,"    Nov.    13,    1902. 
*"Wien.  klin.   Rundsch.,"  Dec.   27,   1903. 
'  "Virchow's  Arch.,"  1905,  Bd.  179,  p.  15. 

•See  Rhodes,  "Jotir.  Amer.  Med.  Assoc,"  Oct.  29,  1904,  p.  1284;  bibho- 
graphy. 


ORGAN'S  OF   RESPIRATION.  569 

cious  anemia,  and  allied  blood  dyscrasias.  Suffocation  and  strangula- 
tion are  also  causes.  Intense  hyperemia  and  extreme  congestion  may 
produce  laryngeal  hemorrhage.  When  the  condition  accompanies  in- 
flammation, it  is  called  hemorrhagic  laryngitis  ;  Garrel  recognizes  three 
forms  of  laryngeal  hemorrhage:  (i)  traumatic,  due  to  injury;  (2)  the 
dyscrasic,  resulting  from  blood  conditions  and  systemic  vices;  and  (3) 
organic,  due  to  ulceration,  tumors,  and  other  pathologic  processes 
affecting  the  larynx. 

Hyperemia  occurs  in  the  initial  stage  of  inflammation,  after  violent 
exercise,  inhalation  of  irritants,  etc. 

Congestion  is  noted  in  heart  disease  and  lesions  obstructing  the 
return  of  lilood  from  the  larynx,  as  goiter  and  mediastinal  tumors. 

Inflammations.' — Inflammation  of  the  larynx  is  called  laryngitis  ; 
of  the  trachea,  trachitis  or  tracheitis.  Catarrhal,  pseudomembranous, 
and  gangrenous  inflammations  occur  in  the  order  given;  the  last  is 
infrequent,  and  the  catarrhal  is  common. 

The  catarrhal  inflammations  may  be  either  acute  or  chronic,  the 
former  depending  upon  exposure,  inhalation  of  irritant  gases,  exten- 
sion of  inflammation  from  adjacent  mucosae,  infections  and  infectious 
diseases,  such  as  measles,  influenza,  etc.  Follicular  distention  and 
superficial  erosions  occur,  but  are  infrequent.  The  vascular  distention 
of  acute  inflammation,  with  even  slight  edema,  interferes  with  the 
function  of  the  vocal  cords,  narrows  the  orifice,  and  is  the  anatomic 
basis  for  the  so-called  spasmodic  laryngitis,  which  is  also  known  as 
spasmodic,  false,  or  catarrhal  croup. 

Chronic  catarrhal  laryngitis  is  usually  a  sequence  of  repeated 
attacks  of  acute  inflammation.  It  is  favored  by  continuous  exposure 
to  irritation,  by  the  presence  of  constitutional  vices, — such  as  syphilis, 
tuberculosis,  contracting  kidney,  gout,  etc., — and  by  local  disturbances 
of  nutrition,  such,  for  example,  as  are  seen  in  the  stagnant  circulation 
of  chronic  heart  disease  and  in  long-continued  pulmonary  inflamma- 
tion, emphysema,  etc.  Epithelial  thickening  (pachydermia  laryngis)  of 
the  vocal  cords,  submucous  cellular  infiltration,  and  even  papillomatous 
excrescences  may  result.  Rosenberg  regards  singer's  nodes  as  results 
of  inflammation  involving  the  duct  of  Frankel's  glands,  and  not  true 
epithelial  indurations  (pachydermia),  as  believed  by  Virchow. 

Pseudomembranous  laryngitis,  or  membranous  croup,-  is  almost  ex- 
clusively dependent  upon  the  bacillus  of  diphtheria,  which  here  rarely 
induces'gangrenous  lesions  similar  to  those  occurring  on  the  pharynx  and 
tonsils.  Menetrier^  reports  a  case  of  membranous  inflammation  of  the  air- 
passages  in  which  an  actively  virulent  pneumococcus  alone  was  found. 
Catarrhal  and  pseudomembranous  inflammations  of  the  larynx  are  some- 
times attended  by  bleeding,  but  altogether  hemorrhages  are  rare. 

Suppurative  laryngitis  occurs  as  a  pustular  manifestation  in  smallpox, 
or  as  a  purulent  infiltration  of  the  submucosa.  most  commonly  secondarv' 
to  an  antecedent  edema  of  that  tissue.  Pus-formation  may  be  diffused 
in  the  submucosa  or  may  be  circumscribed  (abscess);  in  the  latter  case 
it  mav  rupture  into  the  lar\^nx,  infiltrate  the  perilaryngeal  tissues,  or 
dissect  into  the  esophagus.  If  evacuation  be  established  and  drainage 
secured,  repair  may  follow. 

'  See  Patholog>'  of  Inflammation  of  the  Mucous  Membranes,  p.  546. 
'Seep.  550.  '"Soc.  M^d.  des  U6v     '     "—  "  '»-         •    "• 


57° 


SPECIAL  PATHOLOGY 


Catarrhal,  pseudomembranous,  and  gangrenous  inflammations  some- 
times complicate  typhoid  fever. ^  Necrosis  of  the  cartilage  probably 
secondary  to  a  perichondritis  is  the  most  common;  of  Keen's  collection 
of  221  cases,  at  least  89  affected  the  cartilages.  The  condition  is  fatal 
in  about  ninety-five  per  cent,  of  the  patients  in  whom  the  cartilage 
undergoes  necrosis.  Ulcerative  and  suppurative  lesions  are  less  fre- 
quent.     In  some  cases  the  laryngeal  complication  is  due  to  the  typhoid 

bacillus;  in  others  it  de- 
pends upon  concurrent  in- 
fection probably  resulting 
from  the  lowered  resis- 
tance of  the  patient.  A 
typic  typhoid  ulcer  of  the 
larynx  has  been  observed. 
In  some  cases  the  condi- 
tion resembles  Ludwig's 
angina;  the  epiglottis  may 
be  affected. 

Tuberculosis  of  the 
larynx^  may  be  primary 
or  secondary ;  the  latter  is 
the  more  common.  The 
studies  of  Meyer  and 
Ostowsky  indicate  that 
the  bacillus  may  reach 
the  submucosa  without 
any  discernible  lesion  in 
the  overlying  epithelium. 
It  may  begin  by  super- 
ficial erosive  ulceration, 
but  is  usually  manifested 
by  a  tuberculous  infiltra- 
tion of  the  submucosa. 
which  may  be  diffuse  or 
localized ;  in  the  latter  case 
it  resembles  the  chronic 
hyperplastic  tuberculosis.^ 
In  typical  cases  of  this 
form,  sometimes  called 
hvpertrophic,  ulceration 
occurs  late,  if  at  all.  Ac- 
cording to  Theisen,  the 
lesion  is  practically  always 
secondary    to    pulmonary 


Fig.  283. — Pseudomembranous  Laryngitis  and  Tracheitis  due 
TO  THE  Bacillus  Diphtheri.e.  (From  adult  female;  laryn- 
geal diphtheria;  death  on  sixth  day.  The  membrane  extended 
into  the  bronchi.) 

A.  Tip  of  epiglottis,  just  below  which  is  an  irregular  necrotic  area 
continuous  with  the  pseudomembrane.  B.  Edematous  and 
necrotic  mucosa.  C.  Cartilage.  D.  Tracheotomy  wound 
around  which  the  pseudomembrane  has  become  softened  and 
detached;  the  tracheal  cartilages  are  projected  toward  the  ob- 
server as  a  result  of  spreading  open  the  tube.  E.  The  mucosa  at 
and  below  leader  from  letter  E  is  suffused  with  blood.  F.  One 
of  the  tracheal  cartilages.  G,G.  Pseudomembrane  for  the  most 
part  detached  from  underlying  mucosa. 


^  For  fuller  consideration  of  typhoid  affections  of  the  larynx,  see  Keen,  "Sur- 
gical Complications  and  Sequels  of  Typhoid  Fever, "  1898.  Also,  Quinlan,  "  Laryn- 
goscope," Jan.,  190^,  and  Dupuy,  "N.  Y.  Med.  Jour.,"  Dec.  26,  1903,  p.  1226. 

2  Meyer,  "Virchow's  Arch.,"  Bd.  165,  H.  3',  p.  498.  Ostowsky,  "These  de 
St.  Petersburg,"  1900.  Thomson,  "Phila.  Med.  Jour.,"  Sept.  14,  1901.  MoUer 
and  Rappoport,  "Zeit.  f.  Tuberk.  und  Heilstat.,"  July,  1903.  Theisen,  "Amer. 
Jour,  of  Med.  Sci.,"  Nov.,  1903,  p.  833.  Yankauer,  "Laryngoscope,"  St.  Louis, 
March,  1904.  Frese,  "  Miinch.  med.  Woch.,"  March  29,  1904,  p.  552.  Griffin, 
"Med.  Record,"  Dec.   17,   1904,  p.  975.  ^  See  p.    153. 


OKC.AN'S   OF    KKSIMKATIOX. 


571 


iiivolvtMiicnt,  and  may  be  preceded  by  ulcerative  lesions.     Sometimes 
tlu'     h\iiL'r])lasia     is    suf'Hciently    circumscribed     to    justify    the    term 
tuberculoma  of  the  larynx.     Accordinj,'    to    CirifTin,  tuberculous   ulcers 
usually  are  on  the   posterior  wall,  and   be^in   low   and   ascend;   syph- 
ilitic lesions  arise  above  and  descend.       Cicatrization  and  contraction 
are  common  in  syphilis  and  infrequent  in  tuberculosis.     Although  rare, 
svphilitic  and  tuberculous  ulcers  may  be  side  by  side  and  differentia- 
tion of  the  gross  lesions  is  sometimes  impossible.     The  histologic  diag- 
nosis can  be  made  by  the  presence  of  anatomic  tubercles,  or  granulation 
tissue,   containing   the  bacillus.      In  cases 
of  primary  laryngeal  tuberculosis  second- 
arv  invasion  of  the  lung   can  confidently 
be  ])redictcd. 

Syphilis  of  the  larynx'  may  occur  in 
any  stage  of  lues.  Apparently  Moure's 
case  is  the  only  recorded  instance  of  epi- 
glottic chancre.  Mucous  patches  are  some- 
times observed  on  the  epiglottis,  and  less 
commonly  on  the  ventricular  bands;  they 
are  usually  unilateral,  oval  or  elongated, 
whitish  or  yellowish  in  color,  8  to  15  mm. 
in  diameter,  and  marginated  by  a  distinct 
red  areola.  Tertiary  syphilis  of  the  larynx 
may  be  ulcerative,  gummatous,  or  cica- 
tricial. The  last  form  is  the  result  of 
reparative  efforts  in  either  of  the  first 
two.  Syphilitic  ulceration  may  be  rapid, 
but  is  usually  slow;  commonly  cicatriza- 
tion is  present  in  one  area  and  progres- 
sion in  another.  Associated  edema  may 
be  marked,  and  hemorrhage  is  occasionally 
present  but  rarely  severe.  The  ulcera- 
tion may  extend  to  the  perichondrium,  and 
give  rise  to  perichondritis  and  even  necrosis 
of  contiguous  cartilage.  In  a  case  re- 
ported by  Labbe  the  arytenoid  exfoliated, 
was  inspired,  and  caused  death.  A  formed 
sequestrum  may  be  buried  for  years. 
When  cicatrization  occurs,  stenosis  almost 
invariably  follows.  The  gummatous  form 
of  laryngeal  syphilis  may  persist  for 
months  or  even  years  before  ulceration 
appears.  The  necrosis  is  at  first  evident 
near  the  center  and  gradually  extends 
until  the  gummatous  tissue  is  removed. 
If  treatment  be  instituted  early,  ulcera- 
tion may  be  escaped.  Cicatrization  of  the  tertiary  lesions  of  syphilis 
is  commonly  followed  by  intractable  contraction,  giving  rise  [to 
stenosis     (syphilitic     stricture     of     the     larynx).        Sy[)hilis     of     the 

'See  Robertson,  "Jour.  Amer.  Med.  Assoc.,"  Jan.  17,  igo,?:  p.  163.  Conner, 
"Amer.  Jour,  of  Med.  Sci."  July,  1903.  ChaulTard  and  Viollet.  "Gaz.  des  H6p. 
Civils  et  Mil,"  June  9.   1904. 


I'lc;.    384.  — TlBKRCUI.OUS  L'Li  KR    or   THE 

Micous  Mkmbrank  of  thk  Tra- 
ciiKA.  Vkrtkai.  Skction  of  tmf. 
TRAriiEAi.  WAi.t,. — {S-rhmaus.)  X  lo 
diameters. 

A.'.  Cartilage.  e,e.  Kpithclial  layer  of  the 
mucou.s  tnrmbranc.  /.  Tul>crclc3  in 
the  mucous  membrane.  (Submu- 
cf>sa.)    g.  I'Iccr  extcndinn  from  «  to  c 


572 


SPECIAL  PATHOLOGY. 


trachea  is  less  common  than  in  the  larynx;  laryngeal  and  tracheal 
syphilis  are  rarelv  associated  with  pulmonary  manifestations,  while  in 
protracted  cases  of  tuberculosis  the  lungs  never  escape.  Nicholson' 
reports  an  instance  in  which  a  gumma  adjacent  to  the  trachea  com- 
municated with  the  aorta,  and  later,  by  rupture,  gave  rise  to  a  fatal 
tracheal   hemorrhage. 

Leprosy,  actinomycosis,  and  rhinoscleroma  rarely  affect  the  larynx 
and  trachea.     Paratracheal  and  laryngeal  lesions,  in  any  of  these  con- 
ditions,  may   extend    and 


r 


V 


\ 


v.- 


involve    the     structures 
named. 

Perichondritis  is,  as  its 
name  indicates,  an  inflam- 
mation of  the  perichon- 
drium. It  is  usually 
secondary  to  acute  inflam- 
mations of  the  overlying 
mucosa;  less  frequently  it 
results  from  extension  of 
an  infectious  process  from 
the  contiguous  tissues. 
The  condition  is  rarely- 
primary,  commonly  follow- 
ing tuberculosis,  syphilis, 
and  the  more  acute  infec- 
tious diseases,  such  as  ty- 
phoid and  typhus  fevers, 
smallpox,  etc.  Tubes  left 
in  the  trachea,  probably 
by  continuous  irritation, 
may  give  rise  to  inflamma- 
tion of  the  perichondrium. 
Pus  forms  in  the  perichon- 
drium, escapes  through  the 
submucosa  and  mucosa, 
and  an  ulcer  follows  in 
which  exfoliation  of  the 
cartilage  takes  place;  the 
necrosed  cartilage  falls  into 
the  larynx  and  is  expec- 
torated, or  it  may,  acting 
as  a  foreign  body,  reach  a 
bronchus,  or,  lodging  in 
the  air-passage  at  any 
point,  may  give  rise  to 
acute  obstruction.  After 
exfoliation,  in  non-tuberculous  cases,  the  ulcer  tends  to  heal.  In  both 
tuberculosis  and  syphilis  separation  of  the  necrotic  tissue  is  often  slow 
and  may  be  delayed  for  months;  it  is  also  possible  for  a  small  area 
of  necrotic  cartilage  to  be  healed  in  and  remain  quiescent  during  a  long 
period,  or  even  indefinitely. 

'"Lancet,"   Aug.   2,   1902,   p.   293. 


Fig.  285. — Perichondritis,  Necrosis,  and  Laryngeal  Ulcera- 
tion.— ^Specimen  jrom  patient  dead  of  typhoid  fever.) 
The  area  shown  near  the  center  indicates  the  outline  of  an  ulcer,  the 

floor  of  which  was  smooth  and  healing.    Near  the  center  is  seen 

a  black  necrotic  mass  of  e-xfoliating  cartilage. 


ORGAN'S   OF   KESPIkATION. 


573 


Calcification  of  the  cartilages  is  seen  in  the  old,  r;ii<  r.  m  ihe  younj^  or 
niiddk'-aj^'od. 

Edema'  of  the  glottis  may  be  acute  or  clironi'-.     The  acute  form  is 
practicallv  always  inllannnatory  and  may  be  due  to  the  yjncumococcus. 
streptococcus,    pyogenic   staphylococci,  and,  althous^h    less   commonly, 
to   a   few   other   bacteria.     Straussler   and    others    have   described    in- 
stances of  acute  circumscribed  edema,  involving  the  larynx  and  thought 
to  be  of  neuropathic  origin,  resembling  the  nodular  edemas  of  the  skin 
described  by  Quincke.     It  is  generally  conceded  that  acute  primary- 
oedema  laryngis  is  an 
infection   l)y   some  of 
the  bacteria    already 
mentioned.     In  some 
cases    the    exudative 
fluid  is  serous  (serous 
edema),  and  in  other 
instances  the  change 
resembles  dif^'use  sup- 
puration   (phlegmon- 
ous edema).      1-lither 
of   these   may    result 
from  inflammation  of 
the  overlving  mucosa 
or    adjacent    tissues. 
Definite  suppuration, 
in    the    sense     that 
macroscopic    pus    is 
present, rarely  occurs. 
Chronic    forms    of 
edema  of  a  mild  de- 
gree may  suddenly 
manifest  the  charac- 
ters of  an    acute   in- 
flammatory edema. 

Chronic  edema  of 
the  larynx  may  follow 
or  precede  the  acute 
form  or  may  arise  in- 
dependently, the  lat- 
ter being  by  far  the 
more  common.  It 
may  occur  as  a  result 
of  the  venous  disten- 
tion seen  in  valvular 

heart  disease,  and  compression  of  the  veins  returning  from  the  larynx^  by 
tumors,  cvsts,  goiter,  etc.  Pulmonary  emphysema,  dropsical  affec- 
tions associated  with  kidnev  diseases,  or  obstructive  heart  lesions  may 
terminate  fatallv  bv  an  attack  of  edema  of  the  glottis;  chrome 
infectious  processes  in  the  vicinity  are  not  infrequently  attended  by  a 
mild  degree  of  edema.  In  either  form  edema  may  threaten  life  by  occlu- 
'  Straussler.  "  Prag.  med.  Woch."  Nov.  12,  1003.  Rice.  "X.  Y.  Med.  Jour.." 
Dec.  3,  1898,  p.  813. 


Fic.  386.- 


-TRACIIh.VL  .\SV  I'AKTIAL  LAKVNC.t;AI.  STENOSIS  KoLLOWINC  CiCA - 

TKizATios  OF  A  Gumma. 
The  svphililiclcsion  has  evidently  (lcsiri>vf<l  parts  of  two  triiche.il  rinc':   ^n  f 
cxten<ii-<l  upwar.i  into  the  larynx.       Vhc  cartil.isc  -«n  the   nKln 
results  of  a  slowly  proRrrs-sinK  pcriihunilritis.  with  l>e<innini{    i.r 
although  tile  overlying  inucous  membrane  is  not  invtJve^l. 


574 


SPECIAL   PATHOLOGY. 


sion  of  the  passage,  giving  rise  to  a  condition  called  inflammatory  stenosis 
of  the  larynx. 

Laryngeal  stenosis,  exclusive  of  the  malformations,  occurs  in  two 
forms — (i)  functional  and  (2)  organic.  Functional  stenosis  of  the 
larynx  results  from  paralysis  of  the  muscles  that  open,  or  from  spasms 
of  those  that  close  it.  The  former  commonly  follows  faulty  innerva- 
tion, due  to  central  disease  of  the  nerve-trunks,  or  brain,  or  is  secondary 
to  pressure  on  the  nerves  by  tumors,  aneurysms,  etc.  That  paralysis 
may  follow  degeneration  of  the  muscle  without  antecedent  nerve  change 
seems  doubtful.  Organic  stenosis  of  the  larynx  follows  contraction  in 
healino-  ulcers,  notably  the  syphilitic  ulcerations;  laryngeal  tumors, 
edema,  and  inflammations;  pressure  from  without,  as  by  tumors  and 
enlargements  of  the  surrounding  glands,   and  aneurysm.     The  lumen 

may  be  narrowed  as  the  result  of  hemorrhage 
into  the  mucosa,  fracture  or  other  injury  to 
the  laryngeal  structures,  as  in  throttling. 
Laryngeal  obstruction  depending  upon  the 
presence  of  false  membrane,  congenital  hypo- 
plasia, and  foreign  bodies  is  not  correctly 
considered  among  the  stenoses,  although  the 
influence  upon  respiration  is  practically  the 
same. 

Tumors  of  the  Larynx.^ — Adult  Epithelial. 
— Papilloniata  are  by  far  the  most  common. 
They  may  consist  of  fibrous  as  well  as 
epithelial  increase  in  the  papilla,  and  may 
be  soft  and  dendritic,  or  pachydermatous 
and  dense  from  the  thickening  and  subsequent 
hardening.  In  some  cases  multiple  papillomata 
occur;  they  are  usually  small,  often  vascular, 
and  are  sometimes  pedunculated.  Papilloma 
usually  arises  on  or  near  the  vocal  cord  and 
anterior  portions  of  the  larynx,  and  in  some 
cases  the  tumors  are  irregularly  distributed 
over  the  whole  laryngeal  mucosa.  Sometimes 
the  histologic  resemblance  to  cancer  is  striking, 
rendering  the  microscopic  diagnosis  most 
difficult.  All  forms  of  papilloma  are  likely  to 
undergo  transformation  into  cancer. 

Cancers  of  the  larynx  are  usually  epithelio- 
mata;  248  of  486  cases  were  of  the  squamous  type.  Since  Krishaber  made 
the  division  into  intrinsic  and  extrinsic,  systematic  writers  have  generally 
accepted  the  two  forms.  The  intrinsic  laryngeal  cancer  originates  from  the 
true  or  false  vocal  cords,  the  mucosa  of  the  ventricles,  or  less  frequently 
lower  in  the  organ.  Sendziak  found  but  5  subglottic  in  486  cases  of  laryn- 
geal cancer.     The  extrinsic  cancer  arises  from  the  epiglottis  or  other  parts 

'  Haring,  "Brit.  Med.  Jour.,"  Sept.  28,  igoi.  Gleitsmann,  "Med.  Record," 
July  5,  1902.  Harmer,  "Wien.  klin.  Woch.,"  Jahrg.  XV,  June  12  and  19,  1902. 
Fein,  "Wien.  klin.  Woch.,"  July  10,  1902.  Von  Bruns,  "  Beitr.  z.  klin.  Chir.," 
Ixi,  Nos.  I  and  2.  Terry,  "Annals  of  Surgery,"  June.  1904,  p.  968.  de  Santi, 
"Lancet,"  June  18,  1904,  p.  17 10.  Culbert,  "Amer.  Med.,"  July  0.  1904.  Se- 
mon,  "Lancet,"  Nov.  5,  1904,  p.  1263.  Rosenheim  and  Warfield,  '"Amer.  Jour, 
of  Med.  Sci.,"  Jtme,   1904,  p.   1045. 


Fig.  287. — Trachea  of  Child 
(Age  Eleven  Years)  Showing 
Carcinoma  Extending 
through  the  wall  as  an 
Irregular  External  Mass. 

The  trachea  is  markedly  dilated  at 
the  level  of  the  new  growth. 
(I  am  indebted  to  Dr.  Sapping- 
ton  for  the  loan  of  the  speci- 
men from  which  this  drawing 
was  made.) 


ORGANS  OK   KKSIM  RATION'.  575 

of  the  pharynx  or  conti.ijuous  tissue;  it  is  very  nuich  less  frequent  tlian 
the  intrinsic,  and,  in  tlie  larynx,  does  not  exteml  with  such  rapidity. 
Papillomata  occur  in  cliildhood  and  in  adolescence;  cancer  in  middle 
life  or  later.  In  rare  instances  papilloma  accompanies  or  may  even 
follow  carcinoma;  the  association  of  the  two  neoplasms  often  gives  rise 
to  errors  in  diagnosis.  Particles  excised  for  examination  are  likely  to 
he  papillomatous,  antl  hence  the  underlying  cancer  is  overlooked. 

Connective-tissue  tumors  of  the  larynx  are  not  frequent.  Harmer 
and  also  Fein  have  rejiorted  instances  of  lymphangioma.  Fibrous 
polypi,  which  mav  be  hard  or  soft,  have  occasi<jnally  liei'ii  ohserveil. 
Laryngeal  myxoma  and  chondroma  are  rare  tumors.  Sarcoma  of  the 
larvnx  is  occasionally  observed. 

Tumors  of  the  trachea  are  exceedingly  rare;  Schmidt  observed  7 
in  3120  tumors  of  the  upper  respiratory  tract.  The  malignant  growths 
mav  be  primary  or  secondary,  usually  the  latter.  In  an  analysis  of  all  the 
recorded  cases  of  tracheal  tumor  Rosenheim  and  Warfield  found  that 
34  were  papillomata,  ^^  carcinomata,  30  chondromata  and  chondro- 
osteomata,  -\^  hl)r()mata,  and  22  sarcomata.  Thyroid  tumors  (intra- 
tracheal goiter  or  struma)  sometimes  arise  in  the  larynx  or  trachea  and 
are  due  to  ectopic  islands  of  thyroid  gland.  Bruns  reports  5  such 
growths  and  has  been  able  to  collect  6  from  literature;  frequently  they 
show  no  anatomic  connection  with  the  thyroid  gland ;  occasionally  such 
masses  become  cancerous.  Rruns  has  o])cratcd  on  a  malignant  intra- 
tracheal struma. 


BRONCHI. 

Normal  Structure. — The  bronchi  consist  of  a  series  of  tubes  lined 
bv  columnar  epithelium,  which  is  ciliated  down  to  the  terminal  branches, 
in  which  it  becomes  cuboid  and  loses  the  cilia;  the  wall  of  the  bronchus, 
in  addition  to  the  cartilaginous  rings,  is  composed  of  fibrous  and  elastic 
tissue  and  of  a  small  quantity  of  unstriped  muscle,  the  latter  being  most 
abundant  between  the  ends  of  the  imperfectly  encircling  cartilage.  The 
mucous  membrane  of  the  larger  bronchi  contains  numerous  mucous 
glands. 

Malformations. — When  arrest  of  develojmient  has  occurred  i)revious 
to  the  structural  completion  of  the  lung,  the  bronchi  may  terminate 
as  blind  pouches  or  may  be  absent.  Congenital  narrowing  or  the  re- 
verse may  be  found.     (See  Bronchiectasis,  p.  579.) 

Hyperemia  and  congestion  manifest  themselves  under  the  same  con- 
ditions and  induce  changes  similar  to  those  already  described  when 
considering  the  larynx  and  trachea. 

Hemorrhage.     (See  Hemoptysis,  p.  584.) 

Catarrhal  bronchitis,  both  acute  and  chronic,  is  one  of  the  most 
frequent  diseases  of  the  l)ronchi. 

The  investigations  of  Ritchie'  clearly  establish  that  there  is  no  spe- 
cific organism  for  bronchitis,  but  that  the  condition  may  result  from 
infection  by  pneumococci,  streptococci,  and  occasionally  staphvlococci ; 
in  manv  cases  it  is  polymicrobic.  When  accompanying  grippe,  it  is  due 
to  the  Bacillus  influenza?,^  and  occasionally  is  caused  by  the  same  organ- 

'  "Jour,  of  Path,  and  Bact.."  1902,  vol.  vii.  No.  i. 
-  See  y>.   i  26. 


576 


SPECIAL  PATHOLOGY. 


^ 


_^' 


^- 


^.;A 


ism,  and  unaccompanied  by  the  other  symptoms  of  influenza.  Bron- 
chitis frequently  affects  children  and  the  aged.  SilP  states  that  293  of 
1000  sick  children  suffered  from  some  form  of  bronchial  inflammation. 
In  both  extremes  of  life  sudden  temperature  variations,  and  possibly  also 
barometric  changes,  seem  to  bear  a  definite  relation  to  the  occurrence  of 
the  attack.  Bronchial  catarrh  to  some  degree  accompanies  practically 
all  infections  in  which  inflammation  affects  the  upper  air-passages;  it 
is,  therefore,  common  in  diphtheria,  scarlet  fever,  and  particularly 
measles,  and  often  develops  during  pertussis. 

Morbid  Anatomy. — The  changes  observed  in  the  bronchial  mucosa 
are  those  usually  present  in  acute  catarrhal  inflammations  of  a  mucous 

membrane."  Lemoine^ 
states  that  in  an  epi- 
demic of  grippe  he 
observed  18  cases  that 
corresponded  to  the 
type  of  bronchitis 
which  has  been  called 
suffocative  bronchial 
catarrh.  The  path- 
ology of  this  mani- 
festation is  still  a 
matter  of  doubt,  but 
the  clinical  features 
indicate  that  the  in- 
tense asphyxial 
symptoms  are  due  to 
an  unusual  degree  of 
submucous  swelling, 
and  consequent  nar- 
rowing of  the  affected 
tubes.  Bronchial  in- 
fections frequentl}" 
extend  into  the  ves- 
icular structures,  giv- 
ing rise  to  lobular 
pneumonia.  In  the 
larger  tubes  the 
glands  of  the  mucosa 
may  stand  out  prom- 
inently, constituting 
a  follicular  bronchitis. 
When  the  inflammatory  products  are  abundant,  clear,  serous  fluids, 
the  name  bronchorrhea  is  given;  bronchoblennorrhea  is  applied  to  the 
condition  when  a  puriform  expectoration  is  present.  These  probably 
represent  different  stages  in  the  same  inflammatory  process.  Putrid 
or  fetid  bronchitis  is  due  to  decomposition  of  the  bronchial  secretion  by 
saprophytic  bacteria;  it  is  usualh^  associated  with  bronchiectasis,  the 
dilated  cavities  affording  storage  sufficient  to   permit  the  development 

^  "N.  Y.  Med.  Jour.,"  Feb.  6,  1904,  p.  253. 

*  See  Inflammations  of  the  Mucous  Membranes,  p.  546. 

^"Soc.  med.  des  Hop.,"   March  5,   1905. 


Fig.  288. — Lung,  Including  a  Small  Bronchus.  Bronchitis  and  Be- 
GiNTv-iNG  Lobular  or  Bronchopneumonia. 

The  bronchus  (center  of  field)  shows  desquamation  of  epithelium,  many  of 
the  cells  being  completely  detached  and  others  in  process  of  detachment. 
The  bronchial  wall  is  infiltrated  by  mononuclear  leukocytes.  Many  of 
the  adjacent  air  vesicles  contain  a  granular  deposit  resulting  from  pre- 
cipitation, during  fixation,  of  an  albuminous  exudate;  in  this  granular 
material  are  varying  numbers  of  mononuclear  cells  and  epithelial  cells, 
the  latter  having  been  shed  from  the  alveolar  walls. 


ORGANS  OF   RESPIRATION'. 


577 


^ 


% 


^.A 


A, 


^'^_.Ti**«r<i 


/•v^ 


•'SrX-.-. 


■i^& 


v-/ 


M-^^ 


<j 


of  decomposition.  Similar  facilities  are  present  in  pulmonary  gan}.(rene, 
in  empyema  with  perforation  o[  a  bronchus,  in  tuberculous  cavities,  etc. 
By  some  the  condition  is  attributed  to  a  specilic  organism;  by  others, 
to  the  colon  bacillus.  Actinomyces,  oidium  albicans,  aerobic  bacteria  of 
decomposition,  and  possibly  other  organisms  may  be  active  in  producing 
the  accompanying  fetor. 

Chronic  catarrhal  bronchitis  is  usually  a  secjuence  of  rei)eated  at- 
tacks of  the  acute  form.  The  ])ersistence  of  the  bronchial  catarrh  is 
favored  by  systemic  vices  that  disturb  nutrition  or  excretion  or  both; 
the  bronchial  inflammation  accom])anying  gout,  nephritis,  and  diabetes 
belongs  with  this  group.  A  bronchitis  of  varying  intensity  usually 
accompanies  the  chronic  pulmonary  congestion  of  uncompensated 
heart  disease,^  and  is  often  a  part  of  chronic  interstitial  pneumonia, 
emphysema,  and  the  in- 
terstitial changes  asso- 
ciated with  pneumocon- 
iosis. When  the  bron- 
chial inflammation  has 
persisted  for  any  length 
of  time,  there  is  always 
a  tendency  toward  the 
development  of  fibrous 
tissue  around  the 
bronchi — the  peribron- 
chitis chronica  of  Ger- 
man writers.  In  some 
cases  atrophic  changes 
occur  in  the  mucosa, 
converting  the  moist 
mucous,  or  mucopuru- 
lent, forni  into  the  dry 
catarrh.  (See  Fig.  273, 
p.  549.)  Chronic  bron- 
chitis is  a  recognized 
cause  of  bronchiectasis. 
The  relation  of  emphy- 
sema to  chronic  bron- 
chial disease  will  be  con- 
sidered later.      FrankeP 

describcs  a  form  of  bronchitis  affecting  particularly'  the  smaller  l)ronchi 
(bronchiolitis),  attended  by  marked  fibrous  induration  in  the  pulmonary 
tissue  and  obliterating  changes  in  the  bronchioles. 

Fibrinous^  or  pseudomembranous  inflammations  of  the  bronchi  may 
be  acute  or  chronic.  Acute  fibrinous  bronchitis  is  usually  due  to  the 
diphtheria  bacillus  and  frcrjuently  accompanies  diphtheria,  particularly 
the  laryngeal  form.      It  may  also  be  caused  by  the  pneumococcus  and 

'  See  Brown  Indviration  of  the  Lun^  in  Chronic  Heart  Disease,  p.  519. 

*"Deut.  Arch.  f.  klin.  Med.,"  1901,  Bd.  73. 

'  Hochhaus,  "Deut.  Arch.  f.  klin.  Med.,"  vol.  l.xxiv,  Nos.  i  and  2.  Chaplin, 
"  Hunterian  Society,"  Nov.  26,  1902,  also  "Lancet,"  Dec.  13,  1902,  p.  1630. 
Liebermeister,  "Deut.  Arch.  f.  klin.  Med.,"  1904.  vol.  So.  Nos.  5  and  6.  Lange, 
"Deut.  Arch.  f.  klin.  Med.,"  vol.  79,  H.  3  and  4.  Finckh,  "  Beitr.  z.  klin.  Chir.," 
xH,  No.   3. 

38 


^?>-  > 
>..*•'>-    ' 


Fig.  289. — Chro.mc  Caseous  Bronchitis,  Tubercclods  Bronchitis, 
Caseous  Softentnc  of  the  Bronchial  Wall,  with  Thickening 
OF  the  Peribronchi/U,  Tissue,  Peribronchitis  Chronica. — 
(S(^hmaus.) 

ii.  Bronchus  with  thickened  .ind  ca.sociu.s  wall  surrounded  by  a  Liyer  of 
filirinou.s  tissue.  Several  other  lironchi  are  shuwn,  l)Ut  representing 
sliKlilly  different  degrees  of  the  process.  ''•  Transverse  section  of 
interlobular  septum,    c.  Blood-vessel. 


vol. 


578  SPECIAL  PATHOLOGY. 

less  frequently  b}^  staphylococci.  With  regard  to  the  conditions  giving 
rise  to  chronic  fibrinous  bronchitis  we  are  less  fully  informed.  Finckh 
describes  a  pseudomembranous  bronchitis  accompanying  pulmonary 
actinomycosis,  and  it  is  well  known  that  false  membrane  in  the  bronchi 
may  be  a  manifestation  of  chronic  tuberculosis.  Lange  reports  the 
occurrence  of  a  type  of  bronchial  lesion  manifested  by  the  presence 
of  homogeneous  plugs  in  the  bronchioles  sometimes  extending  into  the 
alveoli  and  containing  no  demonstrable  bacteria. 

Morbid  Anatomy. — In  both  the  acute  and  chronic  forms  of  fibrinous 
bronchitis  casts  are  often  expectorated;  they  may  be  fragmentary  or 
represent  a  relatively  large  bronchial  tree.  The  medium  sized  and 
larger  portions  of  the  casts  usually  possess  lumina  that  can  be  recognized 
in  the  gross  specimen.  Smaller  casts  may  be  solid.  Liebermeister  has 
shown  that  they  contain  fibrin  and  that  mucus  may  be  present.^ 

Gangrenous  and  hemorrhagic  inflammations  of  the  bronchi  are  rare, 
and  follow  or  accompany  pulmonary  gangrene,  the  inspiration  of  power- 
ful irritants,  and  the  presence  of  foreign  bodies.  Such  lesions  are 
occasionally  observed  in  pyemia  and  other  septic  manifestations,  and 
sometimes  are  secondary  to  extensions  from  empyema. 

Suppurative  peribronchial  lymphangitis  is  an  inflammation  of  the 
lymphatics  surrounding  the  bronchi.  The  condition  may  follow  pleurisy, 
— more  especially  the  suppurative  form  (empyema), — abscess,  gan- 
grene, septicemia,  pyemia,  and  allied  infectious  diseases.  It  is  not 
recognizable  during  life,  and  postmortem  is  manifested  by  a  purulent 
infiltration  of  the  peribronchial  tissues,  at  times  extending  to  the 
lymphatic  nodes;  if  not  due  to,  it  is  usually  followed  by,  septicemia 
or  pyemia." 

Tuberculosis  of  the  bronchi  is  usually  secondary  to  a  pulmonary 
lesion.  Commonly  it  accompanies  the  chronic  caseous  tuberculosis, 
although  in  the  acute  mihary  form  tubercles  in  the  submucosa  of  the 
bronchus  may  be  observed.  Chronic  caseous  bronchitis  or  peribron- 
chitis is  a  manifestation  of  tuberculosis.  In  the  actinomycotic  peri- 
bronchitis transverse  sections  of  recent  lesions  usually  reveal  the 
fungous  granules.^  According  to  Futterer,*  the  new  tissue  in  the  sub-  - 
mucosa  and  adjacent  structures  possesses  a  sulphur-like  hue  and  lung 
involvement  occurs  late.  SyphiUtic  bronchitis  and  peribronchitis  are 
rare  occurrences  and  are  usually  due  to  an  associated  syphilitic  inter- 
stitial pneumonia. 

Pigmentary  infiltration^  of  the  bronchial  mucosa  and  the  effects  of 
congestion  have  been  studied. 

Stenosis  of  the  bronchi  may  be  due  to  swelling  of  the  mucosa  (bron- 
chial turgescence,  such  as  occurs  in  bronchial  asthma);  to  occlusion, 
more  or  less  complete,  by  fibrinous  exudate  or  mucus;  to  pressure 
from  peribronchial  exudates,  as  in  tuberculosis,  or  to  contraction  of 
newly  formed  cicatricial  tissue,  as  in  syphiUs;  to  intrabronchial  tumors; 
or  to  pressure  from  neoplasms  of  the  lung  or  peribronchial  lymph-nodes 

'  The  structure  and  development  of  these  casts  are  discussed  on  p.  551. 
^  See   Pulmonary   Suppuration,   p.    592. 
^  See  p.   167. 

*"N.  Y.  Med.  Jour.,"  Aug.  24,   1901. 

5  See  Infiltrations  of  the  Mucous  Membranes,  p.  542;  also  Pigmentary  In- 
filtrations,  p.    231. 


ORGANS   or   KK.SPIRATUJX, 


579 


or  from  aortic  aneurysms,  mediastinal  tumors,  and  ii<Mj.i;i>ms  of  the 
esophagus.  Foreign  bodies  may  obstruct  or  occlude  the  bronchi. 
Atelectasis  ami  atrophic  or  inflammatory  changes  occur  in  the  lung 
tissue  beyond  the  point  of  stenosis,  while  bronchiectasis  may  develop 
in  the  bronchus  on  the  trachea  side  of  the  obstruction. 

Asthma'  has  been  attributed  to  (ij  hyperemia  and  (2)  swelling 
of  the  mucosa  of  the  smaller  bronchioles,  and  (3)  to  an  exudative  bron- 
chiolitis. The  recent  studies  of  Brodie  and  Dixon  indicate  that  the 
anatomic  basis  of  acute  asthma  is  spasm  of  the  smaller  bronchi. 

Bronchiectasis,-  or  dilatation  of  a  bronchus,  occurs  in  two  forms 
— (i)  congenital  and  (2)  acquired,  (i)  Congenital  bronchiectasis  is  uni- 
lateral, usually  general,  affecting  many  or  all  of  the  bronchi  of  that 
side  {bronciiicctasis  universalis,  Grawitz).  The  condition  is  a  tubular 
or  cylindric  dilatation  of  the  bronchial  tubes.  It  is  ver\-  rare,  and  the 
cause  is  but  poorly  understood.  (2)  Acquired  bronchiectasis  arises  as 
the  result  of  chronic  bronchial  inflammation,  interstitial  pneumonia, 
atelectasis,  adhesions  of  the  pleura,  tuberculosis,  peribronchial  inflam- 
mations, usually  tuberculous,  or  accumulated  bronchial  secretions. 
Foreign  bodies  in  the  bronchi  and  tumors  may  also  be  causes.  Two 
conditions  are  necessary  in  bronchiectasis:  (i)  Some  lesion  leading 
to  softening  of  the  bronchial  wall;  (2)  a  distending  force.  All  the 
foregoing  offer  these,  and  any  conditions  inducing  them  mav  bring 
about  dilatation.  The  inflammatory  conditions  soften  the  walls,  and 
the  attending  cough  offers  the  distending  force;  where  an  area  of  the 
lung  is  collapsed,  the  bronchus  delivering  air  to  that  part  is  subjected 
to  inspiratory  distention,  and  commonly  dilates.  A  number  of  ob- 
servers have  described  a  form  of  bronchiectasis  involving  the  bronch- 
ioles, and  hence  called  bronchiolectasis.  The  condition  is  said  to 
develop  acutely,  and  hence  is  termed  acute  bronchiectasis,  or  bronchi- 
olectasis. 

As  a  rule,  the  bronchiectatic  cavities  are  fairly  evenly  distributed 
within  the  lung.  In  over  fifty  per  cent,  of  the  cases  but  one  lung  is 
involved.  Any  part  of  the  lung  may  contain  dilated  bronchi,  but  ap- 
parently they  are  most  frequent  in  the  lower  and  middle  lobes.  State- 
ments to  the  contrary  probably  ari.se  from  failure  to  differentiate  the 
cavities  of  tuberculosis  from  those  due  to  bronchiectasis. 

The  bronchiectatic  cavity  may  be  uniform,  cylindric,  or  tubular,  as 
in  the  bronchiectasis  universale;  fusiform,  or  spindle-shaped,  saccular, 
globular,  or  irregular  in  outline;  the  last  is  found  in  bronchiectasis 
due  to  interstitial  pneumonia.  As  one  part  of  the  bronchial  wall  is 
nearly  always  weaker  than  some  other  point,  the  cavity  is  rarelv  svm- 
metric.  The  cavity  of  a  diJated  bronchus  may  be  eight  centimeters, 
or  even  larger,  in  diameter,  and  from  that  size  ilown  to  an  almost  in- 
appreciable dilatation.     The  cavity  may  be  differentiated  from  those  due 

*  "Trans,  of  Path.  Soc.  of  London."  1003,  vol.  liv,  Part  i. 

'  Acldand.  "Practitioner."  April.  1Q02.  Criegem.  "  Ueljer  akute  Bronchiek- 
tasie,"  Leipzig,  iqov  Hondo.  "Centralbl.  f.  allg.  Path.  u.  path.  Anat."  1904. 
No.  3,  p.  i2f).  Edens.  "Deut.  Arch.  f.  klin.  Med.."  1904.  Bd.  Si.  H.  3  and  4. 
James.  "Brit.  Med.  Jour.."  Jan.  2.  1004,  p.  5.  Siewert,  "Bed.  klin.  Woch.." 
Feb.  8.  1004.  Jochmann  and  Moltrccht.  "  Ziegler's  Beitr.."  1904.  Bd.  ^h.  H.  2. 
TutTier,  "Bull,  et  .Mem.  de  la  Soc.  nic-d  dt's  Hop.  de  Paris,"  1899  and  1900.  also 
"Comp.  Rend..  Sect,  de  Path.  Xlllmc  Cong.  Intemat."  Paris.  1901.  King. 
"Jour,  of  Path,  and  Bact.,"  July.  1904.  p.  471.  King,  " Scottish  Med.  and  Surg. 
Jour.,"  June.  1904. 


58o 


SPECIAL  PATHOLOGY 


to  tuberculosis  by  the  following  points : 


In  bronchiectasis  the  wall  may 
be  smooth  and  lined 
with  epithelium,  and 
may  contain,  at  points, 
if  not  throughout,  rem- 
nants of  the  normal 
bronchial  wall;  if  the 
cavity  be  roughened  by 
ulceration,  it  is  at  the 
most  dependent  point. 
The  points  of  entrance 
and  exit  of  the  bronchus 
may  be  seen.  No  shreds 
of  blood-vessels  or  of 
other  bronchi  or  bron- 
chioles are  to  be  seen 
in  the  wail  or  extending 
into  the  cavity.  Recog- 
nition of  the  cause  may 
aid  in  differentiation. 
^  The  absence  of  tubercle 
bacilli  and  of  anatomic 
tubercles  in  the  wall,  of 
course,  excludes  tuber- 
culosis. 

The  cavity  often 
contains  accumulated 
secretion,  and  this  is  fre- 
D  quently  fetid,  owing  to 
saprophytic  infection 
and  decomposition. 
Ulceration  may  open  the 
D  peribronchial  lymph- 
atics and  infection  of 
the  contiguous  tissue 
may  ensue,  giving  rise 
to  pulmonary  abscess 
or  to  gangrene. 

Tumors  of  the  bron- 
chi, as  primary  growths, 
are  exceedingly  rare. 

Bronchioiiths/  so 
called,  rarely  arise  in 
the  bronchi,  although  it 
is  possible  that  inspis- 
sated secretion  might 
calcify  if  retained  suffi- 
ciently long.  Concre- 
tions of  this  kind  usually 
result    from    calcified 

1  Stem,  "Deut.  med.  Woch.,"  1904,  xxx,  No.  39,  1414.     Atlee,  "Amer.  Jour, 
of  Med.  Sci.,"  July,  1901. 


Fig.  290. — Lung,  Emphysema  and  Bronchiectasis.     (Xatural  size.) 

A .  Emphysema  vesicle.     B.  Enlarged  peribronchial  gland.    C.  Enlarged 

peribronchial  gland,  pigmented.     D,  D,  D.  Dilated  bronchi. 


ORGANS  OK   UKSPIUATION'.  581 

tuberculous  areas  or  inlands  wliich  erode  into  the  l)roncln.  The  ex- 
])ectoration  of  lung  stones  is  usually  associated  with  jjulmonary  ex- 
cavation, and  has  been  called  lithogenous  phthisis.  In  the  case  re- 
ported by  Stern  the  patient  couj^dicd  up  ;it  least  twenty  such  calculi. 
Some  of  these  bodies  are  parts  of  exfoliated  cartilaj^^e,  and  it  is  i)robable 
that  all  containing  true  bone  possess  this  origin.  Chcinic  allv  1)r(.n(liio- 
liths  are  composed  of  carbonate  and  phosphate  of  lini- 

Ll.XGS. 

Normal  Structure.  -Tlie  bronchi,  by  dichotomous  division,  event- 
ually ternunate  in  the  infundibula,  around  which  are  arranged  the 
air  vesicles.  The  ciliated  epithelial  cells  lining  the  bronchi  become 
low,  nonciliated,  and  eventually  polygonal  cells,  which,  in  turn,  are 
transformed  into  flat,  pavement-like  cells  in  the  air-vesicle.  The  wall 
of  the  air  vesicle  is  composed  of  fibrous  and  elastic  tissue,  in  which 
ramify  the  capillaries  derived  from  the  pulmonary  artery.  The  nutri- 
tion is  dependent  upon  the  bronchial  circulation.  The  normal  weight 
of  the  lungs  is  subject  to  wide  variations  because,  no  matter  what 
condition  has  given  rise  to  death,  the  slow  circulation  of  the  agonal 
period  gives  rise  to  an  increased  amount  of  blood  and  serum  in  the 
pulmonary  tissues.  It  is  usually  stated  that  the  left  lung,  which  is 
the  lighter,  weighs  from  300  gm.  to  450  gm.,  and  the  right  lung  from 
350  gm.  to  550  gm.  The  studies  of  Spitzka'  on  the  lungs  of  criminals 
executed  by  electricity  show  that  the  normal  left  lung  weighs  from 
216  gm.  to  2S0  gm.,  and  the  right  from  240  gm.  to  350  gm. 

Malposition  of  the  lung  may  be  congenital  or  acquired;  a  lung  that 
has  never  exi)anded  lies  near  the  median  line  ])osteriorly  and  so  oc- 
cupies a  position  that  is  essentially  normal.  In  eventration  of  the 
diaphragm-  the  lung  on  the  affected  side  is  usually  unexpanded  and 
dis])laced  toward  the  apex  of  the  pleural  cavity.  Acquired  malposition 
of  the  lung  results  from  altered  pressure  relations  within  the  thoracic 
cavity  and  al)normal  openings  in  the  wall.  The  most  important  of 
the  pulmonary  malpositions  are  the  hernias  of  the  lung.  Wounds  in 
the  thoracic  wall  may  jjermit  a  lobe  or  part  of  a  lobe  to  escape  the  chest 
cavity.  When  fenestra,  or  wounds,  involve  the  diaphragm,  usually 
an  abdominal  viscus  enters  the  thoracic  cavity;  only  rarely  is  the  hernia 
in  the  opposite  direction.  A  number  of  observers'  have  shown  that 
it  is  possible  for  pulmonary  hernia  to  occur  without  wounds  in  the 
chest  wall.  The  ape.x  of  the  lung  may  rise  in  the  neck  to  an  abnormal 
height,  and  in  rare  cases  a  true  cervical  or  supraclavicular  hernia  may 
occur. 

Malformation^  of  the  lung  is  infrequent.     Absence  of  a  whole  lung 

'  "Proceed,  of  the  Assoc,  of  Amer.  Anatomists,"  iqoj?.  p.  5. 

'  This  condition  is  briefly  described  on  p.  485;  see  also.  Doerinp,  "  Deut.  .Arch, 
f.  klin.  Med..."  1901.  Bd.  72,  H.  5  and  6.  Glaser.  "Deut.  .Xrch.  f.  klin.  Med.," 
1003,  H.  3  and  4. 

'  Rcibold.  "Munch,  med.  Woch.."  March  S,  1004.  p.  4^3.  Bickel,  "Deut. 
.Arch.  f.  klin.  Med.."  Bd.  78. 

*  Springer,  "  Prager  med.  Woch.."  .Aug.  4,  i8q8.  Hanson,  "Jour.  .Amer. 
Med.  .Assoc,"  Sept.  14.  looi,  p.  701.  Neisser,  "Zcit.  f.  klin.  Med.,"  vol.  xlii. 
Lewisohn,  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.."  Nov.  15,  1903.  Humbert. 
"Revue  de   Med.."    1904,    vol.    24.     Ol>envarth,    " Mittheilungen  a.  d.  Grenzge- 


582  SPECIAL  PATHOLOGY. 

or  a  part  of  a  lung,  occasionally  occurs;  absence  of  both  lungs  has 
been  observed.  Additional  lobes  {niultilohulatcd  lung)  have  been  found 
present  in  numerous  instances.  Aberrant  lobes,  or  even  a  miniature 
lung  unconnected  with  any  normal  or  patulous  air-passage,  have  been 
observed.  Hypoplastic  or  underdeveloped  lobules  or  rarely  lobes  have 
been  found,  and  the  reverse  may  occur.  Arrest  of  development  in- 
volving part  of  a  lung,  or  it  maybe  all  of  one  lung,  is  usually  associated 
with  the  corresponding  overdistention  of  the  developed  portion  of  the 
affected  organ,  or  opposite  lung,  constituting  a  compensatory  emphy- 
sema.    (See  Emphysema.) 

Hyperemia  (active  congestion  or  active  hyperemia  of  some  writers) 
occurs  in  violent  exercise,  in  the  initial  stage  of  acute  inflammations 
of  the  lungs  or  pleurae,  in  the  chill  or  cold  stage  of  malarial  and  septic 
paroxysms,  and  in  allied  conditions  that  incite  powerful  cardiac  action; 
excessive  heat  or  cold  is  also  said  to  favor  hyperemia.  It  is  asserted 
that  pulmonary  hyperemia  precedes  death  from  disease  of  the  coron- 
ary arteries;  disease  and  injury  of  the  pons  or  medulla  are  possible 
causes.  Localized  hyperemia  occurs  around  diseased  areas  that  inter- 
fere with  the  circulation,  such  as  infarcts,  circumscribed  catarrhal  or 
croupous  pneumonia,  and  areas  invaded  by  any  of  the  chronic  infectious 
diseases  to  which  the  lung  is  liable. 

If  the  lesion  be  purely  a  hyperemia,  the  condition  to  be  noted  in 
the  initial  stage  of  fibrinous  pneumonia  will  be  found. 

Congestion  (passive  hyperemia  or  passive  congestion  of  some  writers) 
is  dependent  upon  slowing  of  the  pulmonary  circulation  from  (i) 
deficient  force  from  the  right  heart;  (2)  from  non-aeration  of  the  lung; 
(3)  from  increased  tension  in  the  pulmonary  veins,  usually  due  to  im- 
peded progress  in  the  left  heart,  as  in  valvular  disease  of  the  mitral 
orifice,  associated  with  obstruction  or  regurgitation.  In  the  vast  major- 
ity of  cases  more  than  one  of  these  causes  will  be  found  acting.  Two 
forms  of  pulmonary  congestion  are  constantly  observed — (i)  brou-n 
induration  and  (2)  hypostatic  congestion.  Brown  induration  has  already 
been  described.  (See  p.  519.)  It  results  from  disease  of  the  left  heart 
most  commonly,  but  may  be  brought  about  when  any  obstacle  beyond 
the  pulmonary  capillaries  impedes  the  circulation.  Pulmonar}'  edema 
is  frequently  associated  with  chronic  congestion. 

Hypostatic  congestion  arises  as  the  result  of  weakened  heart  action, 
deficient  respiration,  and  the  influence  of  gravity.  It  is  found  in  febrile 
conditions  {e.  g.,  typhoid  fever),  in  the  aged,  and  after  prolonged  stay 
in  the  recumbent  posture,  as  when  a  fractured  limb  is  treated  with 
the  patient  prone. 

This  form  of  congestion  has  also  been  observed  in  morphin-poison- 
ing  and  in  association  with,  or  following,  disease  and  injuries  of  the 
brain;  in  the  latter  case  the  condition  is  further  favored  by  deficient 
movement  or  innervation  of  the  side  affected,  and  is  usually  most 
marked  when  paralysis  is  present.  All  forms  of  coma  favor  the  develop- 
ment of  hypostatic  congestion. 

Being  influenced  by  gravity,  the  dependent  parts  of  the  lung  are 

bieten  d.  Med.  u.  Chir.,"  1904,  Bd.  13,  H.  4  and  5:  also  "Jahrbuch  f.  Kinder- 
heilkunde,"  1904,  Bd.  60.  Hammer,  "Zieg.  Beitr.,"  1904,  Bd.  36,  H.  3.  Cou- 
velaire,  "Revue  Mens,  des  Mai.  I'Enfants,  "  Feb.,  1904.  Otto,  Inaug.  Diss., 
Miinchen,  1904. 


ORGANS  OF  RKSPIUATION.  5^,^ 

principally  involvcil.  The  atTottcd  area  is  dark  in  color,  olten  almost 
black,  much  heavier  than  normal,  ])its  on  ])ressure,  and  when  incised, 
blood  or  bloody  serum  streams  from  the  cut  surface.  The  blood  may 
be  retained  in  the  vessels  and  the  serum  in  the  intervesicular  struc- 
ture, in  which  case  the  affected  area  floats  in  water;  not  uncommonly, 
however,  the  scrum  and  even  some  blood  ])ermeate  the  vesicular  wall 
and  penetrate  the  air  alveolus,  in  which  case  areas  may  be  selected  which 
sink  in  water.  This  latter  condition  has  been  called  splenization  and 
hypostatic  pneumonia.  When  hemorrhage  or  infiltration  of  blood  oc- 
curs in  the  vesicular  wall,  the  chani,'es  observed  may  resemble  those 
seen  in  ditfuse  pulmonary  apoplexy. 

The  gross  anatomy,  as  just  given,  indicates  the  histology.  In  poorly 
marked  cases,  after  hardening,  very  slight  histologic  changes  may  be 
evident;  a  few  leukocytes  and  mucous  cells  in  excess  are  present  in 
the  vesicles;  the  vesicular  epithelium  is  found  cloudy  and  often  des- 
quamating. In  more  marked  cases,  in  addition  to  the  foregoing,  the 
vesicles  contain  more  or  less  blood,  and  infiltration  of  the  pulmonary 
connective  tissue  bv  serum  and  blood  may  be  demonstrable. 

IHilmonary  edema'  mav  be  general  or  local,  acute  or  chronic.  The 
acute  may  be  further  divided  into  the  acute  simple  and  the  acute  ful- 
minating. Acute  fulminating  pulmonary  edema  appears  suddenly,  some- 
times when  the  previous  health  has  given  no  warning.  Arteriosclerosis 
is  usuallv  present  in  this  as  in  other  forms  of  edema  of  the  lung,  and 
in  most  cases  there  is  also  a  chronic  interstitial  nephritis.  Brouardel 
does  not  recall  having  seen  a  case  of  pulmonary  edema  without  renal 
lesions;  Allbutt  has  noted  its  association  with  aortitis.  The  condition 
mav  be  produced  experimentally  by  the  administration  of  adrenalin. 
This  hyperacute  form  may  run  its  course  and  tenninate  fatally  within 
an  hour.  At  the  autopsy  the  lungs  are  found  hyperemic.  in  areas 
inundated,  and  the  bronchi  filled  with  a  reddish,  frothy  mucus.  Should 
the  patient  survive  a  single  attack,  recurrences  are  not  infrequent. 
The  patient  reported  by  Lissaman  had  seventy-two  attacks  in  two  and 
a  half  years;  during  one  attack  1260  c.c.  of  iiuid  was  expectorated  in 
eight  hours.  The  simple  acute  pulmonary  edema  appears  with  less 
rapiditv  and  is  rarely  so  intense.  The  bronchial  contents  and  sputum 
are  not  so  red,  although  the  quantity  of  albumin  is  usually  greater. 
It  occurs  especiallv  in  connection  wifli  pulmonary  congestion,  nephritis, 
arteriosclerosis,  and  cardiac  failure.  It  may  accompany  violent  septic 
processes  and  pulmonar\'  embolism.  Anatomically  the  lung  is  the 
seat  of  changes  essentially  similar  to  those  in  the  next  form  to  be  des- 
cribed. Chronic  pulmonary  edema  is  observed  in  Bright's  disease,  par- 
ticularlv  chronic  parenchymatous  nephritis.  It  may  also  be  caused  by 
chronic  pulmonarv  congestion,  profound  anemias,  mediastinal  tumors, 


'  The  principal  data  concerning  pulmonary  cdcina  can  be  obtained  from  the 
following  references:  Meltzer,  Harrington  Lectures.  University  c)f  BulTalo,  1904; 
also     Amer.  Med.."  July  2.  9,  23.  and  30,  1904.     Owen,  "Brit.  Med.  Jour 


p.  145.     Hewlett.  ■•  Intercolon.  Med.  Jour.."  Dec.  22,  1903,  p.  611.     von  Rieck- 
hofl,    Inaug.    Diss.,  Munchen.    1904.    Josu6.     "La   Presse    Mfed."  Jan.   21,   1905. 


p.  41. 


584  SPECIAL  PATHOLOGY. 

and  in  anv  condition  in  which  the  death  agony  is  prolonged.  The  pul- 
monary edema  associated  with  albuminous  expectoration  and  follow- 
ing thoracocentesis,  usually  resembles  the  acute  simple  form  of  edema 
of  the  lungs,  but  may  possess  some  of  the  characters  of  the  chronic 
form.  Chronic  pulmonary  edema  is  usually  held  to  be  the  result  of 
increased  tension  in  the  capillaries  of  the  lung,  associated  with  changes 
in  the  endothelium.  There  is  a  growing  belief  that  it  may  be  due  to 
infection;  Blumer  has  found  that  such  lungs  frequently  contain  bac- 
teria. 

Morbid  Anatomy. — In  marked  cases  the  whole  lung  is  affected,  but 
all  parts  are  not  involved  to  the  same  degree;  the  lesion  is  most  in- 
tense in  the  dependent  areas.  The  lung  pits  on  pressure,  does  not  al- 
ways crepitate  throughout,  is  often  boggy,  and  is  always  more  succu- 
lent than  normal.  In  the  absence  of  hyperemia  the  organ  is  pale,  but, 
as  the  blood-content  is  nearly  always  increased,  the  color  is  commonly 
dark.  As  soon  as  incised,  serum,  which  is  usually  blood-stained  and 
frothy,  streams  from  the  cut  surface.  The  greatly  increased  weight 
is  clearly  due  to  the  large  amount  of  serum  and  excess  of  blood  in  the 
organ;  usually  the  lung  crepitates  throughout,  but  in  marked  cases 
selected  areas  may  be  airless.  In  such  cases  the  air-vesicles  may  be 
filled  by  transuded  serum,  or  it  is  possible  that  serum  in  the  bronchi 
may  be  aspirated  into  and  fill  the  lobules.  It  is  rare  for  large  areas 
to  be  solidified.  Microscopically  the  vascular  distention  is  often  slight, 
but  may  be  marked.  The  interstitial  tissues  are  separated  and  many 
of  the  air-vesicles  contain  serum  and  a  few  cells.  In  the  absence  of 
infarction  red  cells  are  never  abundant  in  the  alveoH.  There  is  nearly 
always  more  or  less  evidence  of  bronchitis,  which  is  catarrhal  in  type. 
Sometimes  at  autopsy  the  lungs  are  gelatinous  and  trembling,  and  in 
such  cases  I  have  found  a  small  amount  of  fibrin  which  may  be  an 
evidence  of  postmortem  coagulation  of  the  edema  fluid. 

Localized  pulmonary  edema  occurs  around  neoplasms,  infarcts,  and 
acute  inflammatory  and  tuberculous  areas  in  the  lung.  The  condition 
is  sometimes  called  collateral,  circumscribed,  or  focal  edema,  and  is 
always  determined  by  some  local  lesion. 

Hemoptysis,  also  'called  blood-spitting,  bronchopulmonary  hemor- 
rhage, or  simply  pulmonary  hemorrhage,  may  be  due  to  falls,  blows 
upon  the  chest,  wounds  of  the  lung  or  bronchi,  or  other  forms  of  trauma. 
The  most  common  cause  is  tuberculosis,  in  which  condition  the  hemor- 
rhage mav  be  due  to  mihary  or  ulcerative  lesions  of  the  air-passages, 
or  the  rupture  of  vessels,  whether  aneurysmal  or  not,  in  cavities.  Weis- 
mayr^  strongly  urges  the  older  belief  that  most  of  the  hemorrhages 
are  due  to  aneurysms  in  caseous  cavities.  Any  form  of  laryngeal, 
tracheal,  or  bronchial  ulceration  in  which  a  bronchial  artery  is  opened 
may  be  a  cause.  Bronchiectasis  rarely  gives  rise  to  hemoptysis.  In 
pulmonary  congestion,  such  as  accompanies  heart  disease,  and  in  hyper- 
emia of  beginning  pulmonary  inflammation,  slight  hemorrhages  some- 
times occur.  In  malignant  tumors  of  the  lung,  or  tumors  involving 
the  bronchi,  trachea,  -or  larynx,  hemoptysis  is  occasionally  observed. 
Leprosy  and  actinomycosis  may  be  mentioned  among  the  rare  causes. 
Pulmonary  abscess  and,  especially,  gangrene  of  the  lung  often  give 
rise  to  bleeding  which  may  be  fatal.  Aneurysm  of  the  pulmonary 
i"Wien.   klin.   Rundschau,"   April   20,    1902. 


ORGAN'S  OF  RESPIRATION.  585 

artery  or  its  branches,  of  the  ac^rta,  innominate,  internal  carotid,  or 
even  the  subclavian,  may  ru[)ture  into  the  air-passages.  Rarely  the 
hemorrhage  is  vicarious.  Hemoptysis  is  occasionally  observed  in  hys- 
teria; Pende'  has  reported  an  instance  of  fatal  hysteric  hemoptysis  in 
which  no  lesion  could  be  found  in  the  lung  at  autopsy.  Pulmonan* 
hemorrhage  is  sometimes  observed  in  purpura,  scurvy,  and  occasion- 
ally in  leukemia.  In  pulmonary  distoniatosis- — enflemic  hemoptysis 
of  China  and  Japan — hemorrhage  constitutes  a  conspicuous  symptom. 
Wright  believes  that  in  hemoptysis  the  inordinate  hemorrhage  often 
depends  upon  lessened  coagulability  of  the  l)loo(l.  Reed^  reports  an 
instance  of  synchronous  bilateral  pulmonary  hemorrhage  brought  about 
by  a  heavy  lift.  At  the  autopsy  extensive  interstitial  hemorrhage  was 
found  in  the  central  portion  of  both  lungs;  anatomically  the  lesion 
resembled  an  infarct.  In  a  certain  number  of  cases  no  assignable  cause 
can  be  found;  in  a  few  of  these  the  hemorrhage  may  recur  a  number 
of  times  without  any  discernible  organic  lesion  preceding,  accompany- 
ing, or  following  it.  To  this  class  properly  belong  vicarious  hemo- 
ptysis, as  well  as  that  which  may  accompany  pregnancy;  in  the  latter 
instance  cases  are  recorded  in  which  successive  pregnancies  have  been 
accompanied  by   recurring   hemoptysis. 

The  effect  of  hemoptysis  may  be  local  or  general,  "-ocally,  a  slowly 
manifested  hemorrhage  may  be  aspirated  into  the  air-vesicles  and 
gradually  inundate  the  bronchial  system;  a  marked  or  severe  hemor- 
rhage may  rapidly  flood  the  respiratory  passages  and  be  immediately 
fatal.  The  hemorrhage  can  develop  so  slowly  that  no  phenomenon 
during  life  is  observed,  and  postmortem  much  of  the  lung  may  be 
found  filled  with  the  effused  blood.  If  large  cavities  are  present 
in  the  lung,  a  fatal  hemorrhage  may  fill  them  and  cause  death  with- 
out any  blood-spitting.  The  general  phenomena  are  those  of  shock. 
If  death  occur  during  the  attack,  the  lung  postmortem  is  more  or  less 
distended  or  inundated  with  blood;  antemortem  and  postmortem  coagula 
\v\\\  be  found  in  cavities,  when  such  are  present,  as  well  as  in  the 
bronchi.  As  the  patient  does  not  commonly  die  from  the  hemorrhage, 
the  causes  ma\'  l)e  of  more  interest  than  the  condition. 

Hemorrhagic  infiltration,  or  infarction*  {pnluionary  embolism,  or 
pulmonary  apoplexy),  consists  in  an  arrest  of  the  circulation  in  a  given 
area  of  the  lung,  vascular  rhexis  with  infiltration  of  the  intervesicular 
structure,  and  effusion  of  blood  into  the  air-vesicles. 

The  condition  results  from  occlusion  of  a  branch  of  the  pulmonary 
artery  by  a  thrombus  (autochthonous  embolism)  or  an  embolus.  The 
latter  usually  reaches .  the  heart  from  the  venous  circulation,  as  in 
phlegmasia  alba  dolens,  or  arises  in  the  heart,  notably  the  right  auricle. 
The  processes  of  thrombosis  and  the  origin  of   emboli  have  been  con- 

'  "Morgagni,"  July  q,  1904.     "Munch,  med.  Woch.."  Oct.   25,  1004,  p.  i93***- 

'  See  p.  192. 

'  "Western  Med.  Review,"  July  15,  1902.  vol.  vii.  No.  7. 

♦  Gebele.  "  Beitr.  z.  klin.  Chir..""  von  Bruns.  Tubinpen.  1904.  xliii.  \o  2. 
Oppenheimer.  "Bed.  klin.  Woch.."  Feb.  3.  1902.  Keves.  "  N*.  Y.  Med.  Jour.." 
April  5.  1902.  Miller,  "Amer.  Med.,"  Aup.  2,  1902.  McPhedran  an<l  Mackenzie, 
"Trans,  of  the  Assoc,  of  Amer.  Physicians,"  1903.  Tiedemann,  "Zeit.  f.  klin 
Med,"  Bd.  50.  Hodlmoser,  "Zeit.  t.  Heilk.."  Bd.  xxv,  H.  5.  p.  109.  Hadcler. 
Inaug.  Diss..  Munchen.  1904.  Connell.  Amer.  Med.  Assoc..  Section  in  Sur- 
gery. June  10.  1904:  also  "Med.  Record."  July  2.  1904.  p.  39.  Robinson.  "Med. 
Record."   Jan.    14.    1905. 


586 


SPECIAL  PATHOLOGY. 


sidered.  (See  p.  278.)  Where  a  thrombus  forms,  fibrinous  plugs  oc- 
clude the  vascular  supply  to  the  affected  part,  and  a  cone-shaped  area 
marks  the  outlines  of  the  infarct.  With  clearly  formed  areas  of  hemor- 
rhage, not  to  be  differentiated  from  known  areas  of  infarction,  some- 
times no  embolus  or  thrombus,  or  source  of  either  of  these  bodies,  can 
be  demonstrated.  Feebleness  of  the  circulation  favors  the  occurrence 
of  pulmonary  infarcts. 

Morbid  Anatomy. — Postmortem,  the  changes  found  depend  some- 
what upon  the  extent  of  the  area  involved  and  upon  the  age  of  the 
infarct  and  its  character. 

When  the  lodged  embolus  is  massive,  occluding  the  pulmonary 
artery  at  its  bifurcation,  and  when  death  occurred  immediately  upon 

its  lodgment,  the  lung  does 
^  not  show  the  condition  here 
considered  as  pulmonary 
apoplexy;  it  may  manifest 
no  conspicuous  change.  In 
typical  cases  of  recent  em- 
bolism the  infarct  appears, 
under  the  pleura,  as  a  dark- 
red,  almost  black,  mass,  vary- 
ing in  diameter  from  one 
centimeter  to  five  centimeters, 
rarely  larger,  and  on  section 
is  found  to  be  more  or  less 
wedge  shaped,  truly  conic, 
with  the  apex  of  the  cone  di- 
rected toward  the  center  of 
the  lung.  The  color  of  the 
affected  area  varies  from  a 
gray,  in  extremely  leukemic 
blood,  to  a  black;  as  the 
process  grows  older  the  color 
passes  from  black  to  reddish- 
brown,  and,  with  the  gradual 
resorption  of  blood  coloring- 
matter  and  resolution,  the 
normal  color  may,  in  favor- 
able cases,  return.  While  the 
typical  pulmonary  infarct  is 
conic  or  wedge  shaped  on  sec- 
tion, the  extensive  anastomosis  of  the  pulmonary  circulation  often 
affords  so  abundant  a  collateral  blood  supply  that  the  area  may  be  almost 
globular,  or  pear-shaped,  and  ovoid  on  section.  The  pleura  over  the 
area  is  at  first  normal,  but  soon  shows  a  beginning  exudate.  Many  post- 
operative pleurisies  are  of  embolic  origin.  There  is  usually  considerable 
edema  surrounding  the  infarct.  If  the  process  is  not  infected — it  is  the 
noninfected  variety  which  is  now  under  consideration — and  the  area 
is  small,  absorption  is  possible.  It  is  probable,  however,  that  a  certain 
amount  of  cicatricial  tissue  always  develops,  and,  in  not  a  few  instances, 
a  fibroid  area  remains. 

Histologically,  the  area  consists  of  plugged  vessels,  with  blood  in- 


FiG.    291.— Lung,  HiMni,  I'll  \^.i'     Kjarct.     (Natural    Size.) 
.4.  pleura.     B.  Small  infarct  centrally  placed.     The  large  in- 
farct shows  the  elevation  of  the  pleura,  the  hemorrhagic  suf- 
fusion of  the  central  area,   and  the  periphery  of  inflam- 
matory hyperemia. 


OKGANS   OF   RKSPIKATIuX.  5H7 

liltratctl  into  the  septa  antl  vesicles.  In  a  shcjrt  tune  utter  the  inliltra- 
tion  the  red  corpuscles  undergo  hemolysis,  disintegrate,  and  the  result- 
ing pigment  diffuses  into  the  adjacent  tissue.  The  leukocytes  increase 
in  number,  and,  if  the  area  involved  be  small,  the  jjroducts  may  pass 
off  bv  the  Ivmphatics.  which,  in  many  cases,  become  permanently  pig- 
mented by  the  process.  If  the  area  be  larger  and  the  tissue  reaction 
greater,  some  fibrous  tissue  results;  in  more  marked  cases  a  puckered, 
pigmented,  fibrous  area  forever  marks  the  site  of  the  lesion.  If  the 
bronchial  artery,  as  well  as  the  branches  of  the  pulmonary  artery,  be 
occluded,  the  area  may  undergo  a  simple  softening,  fibroid  change  may 
occur  around  it,  and  lime  salts  may  infiltrate  it.  The  embolus  causing 
the  process  mav  organize  in  situ  and  permanently  occlude  the  vessels, 
or  resolution  may  occur. 

If  the  embolus  contained  bacteria,  or  should  the  area  of  the  infarct 
become  infected  by  organisms  capable  of  inducing  suppuration,  an  ab- 
scess results;  if  the  saprophytic  bacteria  gain  ingress  and  survive,  gan- 
grene mav  be  engendered ;  if  the  embolus  represented  a  part  of  a  malig- 
nant tumor,  a  new  focus  of  development  is  assured.  Emboli  contain- 
ing the  micro-organisms  of  the  chronic  infections  lead  to  secondary 
nodules  in  the  lung.  The  emboli  associated  with  the  latter  processes 
— abscess,  gangrene,  neoplastic  growth,  and  chronic  infections— are  so 
small  that  little  hemorrhagic  infiltration  may  accompany  them. 

Pulmonary  atelectasis  occurs  in  two  forms — the  congenital  and  the 
accjuired. 

Congenital  atelectasis,  or  apneumatosis,  is  that  condition  of  the 
lungs  resulting  from  failure  t<j  expand  following  birth,  the  organ  re- 
taining its  fetal  characters. 

The  lungs  may  fail  to  expand  as  the  result  of  inefficient  resjnratory 
effort  or  weakness.  Extremely  feeble  infants  may  not  be  able  to  ex- 
pand the  whole  lung.  The  condition  may  also  result  from  plugging 
of  a  bronchus  by  aspirated  solids,  or  even  fluids,  during  delivery.  If 
the  infant  survive  for  some  weeks,  the  imperforate  bronchi  associated 
with  the  collapse  will  usually  show  dilatation  in  the  affected  area,  the 
extent  of  the  dilatation  depending  ui)on  the  duration  of  life  and  the 
amount  of  inspiratory  force  which  the  child  has  been  able  to  exert. 

Morbid  A)tato))iy.^—The  condition  may  involve  a  part  or  the  whole 
of  one  lung,  or  may  be  scattered  as  irregular  foci  in  l)Oth  lungs.  The 
areas  of  atelectasis  are  usually  most  abundant  and  largest  posteriorly 
in  the  lower  lobes.  When  the  collapse  has  been  due  to  inefficient  res- 
piratorv  efforts,  the  introduction  of  air  through  a  blowpipe,  inserted 
into  the  bronchus,  vnU  usually  lead  to  expansion.  When  the  atelec- 
tasis is  the  result  of  mechanical  obstruction  by  foreign  bodies,  the 
collai)sed  areas  can  not  be  fully  expanded  in  the  manner  just  described. 
The  atelectatic  portions  are  darker  in  color  than  the  surrounding  ex- 
panded lung,  do  not  crepitate,  and  sink  in  water.  When  the  areas 
are  small  and  not  abundant,  the  infant  may  recover;  under  such  cir- 
cumstances gradual  distention  may  be  brought  about,  or  degenerative 
or  proliferative  changes  may  lead  to  connective-tissue  substitution, 
followed  by  contraction,  and,  in  time,  but  little  evidence  of  the  lesion 
mav  remain. 

Acquired  atelectasis,  f)r  collapse,  is  the  condition  observed  when  a 
part  of  the  lung  which  has  once  expanded  loses  its  air  and  does  not  refill. 


e88  SPECIAL  PATHOLOGY. 

Pulmonary  collapse  results  from  the  introduction  of  gas,  fluids,  or 
solids  into  the  pleura,  the  first  arising  from  puncture  of  the  lung  or 
chest-wall,  or  both;  the  second  from  pleuritic  effusions,  dropsical  or 
inflammatory,  or  hemorrhage  into  the  pleura;  the  third  from  tumors. 
Bronchial  obstruction  is  a  frequent  cause ;  the  occlusion  may  be  due 
to  a  foreign  body,  a  mass  of  false  membrane,  a  clot  of  blood,  or  a  plug 
of  mucus;  the  bronchus  may  be  collapsed  by  pressure  from  without, 
as  when  an  enlarged  peribronchial  lymph-node,  tumor,  or  aneurysm 
presses  upon  it.  The  influence  of  pressure  may  be  shown  in  aortic 
aneurysm,  pericardial  distention,  mediastinal  tumors,  spinal  curvature, 
etc.;  the  pressure  may  be  insufficient  and  the  atelectasis  partial  at 
first,  but  if  the  cause  continues  to  act,  the  collapse  becomes  complete. 
When  due  to  bronchial  obstruction,  the  condition  is  called  obturation 
atelectasis;  collapse  resulting  from  external  pressure  is  known  as  com- 
pression atelectasis . 

Morbid  Anatomy. — When  the  collapse  aftects  the  whole  lung,  as 
in  pleurisy  with  effusion,  the  organ  is  pressed  upwar(i  and  toward  the 
mediastinum  and  against  the  spine.  The  organ  or  the  affected  area 
is  pink  or  pale  gray  in  color,  is  firm  and  airless,  is  tough,  tearing  with 
difficulty,  and  often  can  not  be  distended;  firm  adhesions  may  bind 
it  down,  and  the  pleura  may  have  become  so  thickened,  fibroid,  and 
resisting  that  reexpansion  can  never  occur.  When  small  areas  of  col- 
lapse occur,  as  in  bronchopneumonia,  in  the  recent  state,  they  appear 
as  small  depressed  spots,  immediately  under  the  pleura,  bluish-purple 
or  bluish-brown  in  color;  occasionally  lividity  develops  on  exposure 
to  the  air;  surrounding  these  areas  the  vesicles  are  distended  (com- 
pensatory emphysema)  and  are  pink  or  reddish-white,  in  contrast  to 
the  darker  collapsed  portions.  If  the  collapse  be  recent  and  the 
occluded  bronchus  not  too  firmly  obstructed,  a  blowpipe,  or  even  firm 
pressure  on  the  surrounding  areas,  may  refill  the  collapsed  vesicles. 
Later,  from  stasis  in  the  vesicular  wafl,  the  color  becomes  much 
darker,  and  blood  escapes  into  the  connective  tissue;  the  mass  is  soft 
and  resembles  the  spleen  in  texture  (splenization).  Later,  the  blood 
to  a  certain  extent  is  absorbed,  the  vesicular  walls  coalesce,  prolifer- 
ated connective-tissue  cells  and  leukocytes  form  a  _  young  cellular 
tissue,  and  the  mass  is  now  in  the  condition  called  carnification.  With 
the  completion  of  contraction  and  organization  a  firm  fibroid  area  re- 
sults, known  as  the  cirrhosis  of  collapse  ;  these  areas  contain  a  relative 
excess  of  pigment,  are  pink  at  first,  later  gray,  and  are  said  to  show 
gray  induration. 

Emphysema  is  a  condition  characterized  by  an  excess  of  air  in  the 
lung.  Two  forms  of  the  affection  are  recognized:  in  one  the  excess 
of  air  is  in  the  connective  tissue  of  the  organ ;  in  the  other  it  is  in  the 
overdistended  vesicles. 

Interstitial  emphysema,  also  called  interlobular  emphysema,  is  a 
condition  in  the  lung  comparable  to  subcutaneous  or  surgical  emphy- 
sema involving  the  subcutaneous  structures  in  fracture  of  the  nose,  or 
to  the  gas  generated  in  the  tissues  in  some  forms  of  gangrene. 

The  condition  usually  results  from  ruptured  air-vesicles,  and  oc- 
casionallv  occurs  in  violent  coughing,  as  in  whooping-cough,  or  bursting 
of  distended  air-sacs  in  vesicular  emphysema.  It  is  frequently  due  to 
pulmonarv  injury  resulting  from  fractured  ribs  and  penetrating  wounds 


ORGANS  OF   RESPIRATION.  589 

of  the  chest.  In  the  hitter  condition  interstitial  emphysema  may  occur 
without  pneumothora.K,  provided  air  does  not  i^uin  inj^ress  throuj^h 
the  thoracic  wall.  It  has  recently  been  shown  that  pneumothorax 
may  result  from  infection  of  the  pleura  by  the  Bacillus  aeroj^enes  cap- 
sulatus  of  Welch.  It  is  probable  that  in  a  similar  manner  an  inter- 
stitial pulmonary  emphysema  mij,dit  be  induced. 

Morbid  A}iato))iy. — ^Interstitial  em])hysema  may  be  readily  detected 
postmortem  by  the  larj^e  blebs  found  immediately  under  the  pleura, 
differing  from  overdistendetl  air-vesicles  in  that  the  former  can  be 
pushed  around  from  place  to  place  beneath  the  serosa.  When  the 
rujiture  occurs  near  the  root  of  the  lung,  not  only  does  the  air  reach 
the  surface  of  the  organ  by  the  interlobular  connective  tissue,  but  it 
may  rind  access  to  the  mediastinal  structures  and  the  connective  tissue 
of  the  neck. 

Vesicular  emphysema  is  a  condition  in  which  the  alveoli  and  in- 
fundibular passages  are  dilated. 

When  the  emphysema  consists  of  overdistended  vesicles  in  one  area 
occupying  the  space  and  receiving  the  air  that  should  be  distrilmted 
in  another  part  of  the  lung,  the  condition  is  spoken  of  as  local,  vicar- 
ious, or  compensatory  emphysema.  As  the  condition  may  be  acute, — 
c.  i^.,  around  an  atelectatic  area. — the  withdrawal  of  the  cause  termi- 
nates the  emphysema;  when  the  cause  persists,  the  acute  dilatation 
becomes  permanent;  at  first  there  may  be  no  wasting,  but  eventually 
the  intervesicular  septa  atrophy  and  this  form  passes  into  true  em- 
physema. 

Substantive,  substantial,  idiopathic,  hypertrophic,  or  large-lunged 
emphysema'  is  a  well-marked  condition,  readily  recognized  clinically, 
and  possessing  pathologic  lesions  eminently  its  own. 

Causes. — There  seems  to  be  necessary  a  hereditary  tendency,  a 
congenital  deficiency  in  the  lung  tissue,  in  the  absence  of  which  em- 
physema is  not  likely  to  occur.  Exactly  what  constitutes  this  heredi- 
tary' deficiency  has  not  been  determined;  the  view  that  it  is  a  defect 
in  the  elastic  tissue  is  entirely  consistent  with  the  facts,  but  probably 
is  not  demonstrable.  In  two  instances  observed  by  Orth  the  appear- 
ances suggested  a  congenital  hypoplasia,  and  he  is  of  the  opinion  that 
some  pulmonary  injury  or  developmental  defect  modifying  the  elas- 
ticitv  of  the  organ  is  the  essential  factor  in  the  production  of  emphy- 
sema. The  disease  is  hereditary,  in  the  .sense  indicated,  and  results 
from  tissue  peculiarity  transmitted  from  the  parent.  Given  the  first 
element, — congenital  weakness  of  the  vesicular  structures, — the  second 
is  heightened  intra  vesicular  tension.  This  may  be  brought  about  in 
two  ways — (i)  inspiratory  and  (2)  expiratory. 

I.  Inspiratory  Distention. — The  vesicular  distention  of  compensatory 
emphysema  is,  of  course,  inspiratory;  and  as  true  vesicular  emphysema 
is  almost  always  associated  with  catarrhal  lesions,  which  favor  atelecta- 
sis, the  possibility  of  inspiratory  distention  acting  as  the  cause  can 
not  be  overlooked.      The  constant  association  of  catarrhal  inflammation 

'Campbell,    'West   London    Med.    Jour.."    July,    iSq?,  p.   190.     Collingwood. 
Med.  Soc.  of   London.  "  Jan.  12.  1903;    also  "Brit.  Med.  Jour.."  Jan.  17,  1903. 
y.  139.     Prettin  and  Leibkind,  "Munch,  med.  Woch.,"  Feb.  9,  1904,  p.  259.     Con- 
ford.  "Brit.    Med.    Jour.,"  June  25,   1904,  p.    14S5.     Orth.  "Berl.  klin.  Woch.," 
Jan.  2,  1905.     Malibran,  "La  Presse  M6d.,  '  Sept.  3.,  1904,  p.  563. 


590 


SPECIAL    PATHOLOGY 


and  the  plugging  of  bronchioles,  attended  by  collapse  in  the  lobules 
supplied,  leads  to  compensatory  dilatation  of  adjacent  vesicles,  and 
eventually  to  overdistention  of  these  structures.  The  plug  of  mucus 
now  shifts,  and  another  series  of  vesicles  are  expanded  beyond  their 
normal  limits.  These  processes,  frequently  repeated,  so  overdistend 
the  elastic  tissue  of  the  vesicular  wall  that  the  normal  retractile  power 
is  lost  or  modified,  and  the  air -vesicles  are  thereby  rendered  incom- 
petent fully  to  empty  themselves.  The  foregoing  views  with  regard  to 
the  inspiratory  hypothesis  have  been  modified,  and  in  part  supplanted 
by  the  theory  to  be  next  discussed. 

2.  Expiratory  distention  acts  by  increased  pressure  applied  to  the 
lung  by  the  thoracic  wall,  and  coincident  abnormal  resistance  to  free 
exit  of  the  expired  air  brought  about  by  narrowing  of  the  laryngeal 
chink,  glottis,  epiglottidean  lumen,  etc.  During  the  violent  expiratory 
effort  incident  to  severe  coughing,  the  costal  cartilages  and  sternum 
are  pushed  forward,  the  extreme  normal  obliquity  of  the  ribs  is  altered, 
and  the  pulmonary  space  at  the  apex  is  increased,  thus  permitting  dis- 
tention of  the  lungs  at  the  apex  or  upper  lobes  and  the  anterior  mar- 
gins, these  points  showing  the  most  marked  change. 

The  causes  active  in  increasing  the  expiratory  stress  are:  (i)  Coughs, 
as  in  chronic  bronchitis,  the  violent  respiratory  strain  of  pertussis,  etc. 
The  fact  that  whooping-cough  increases  the  vesicular  tension  is  shown 
by  the  occurrence  of  interstitial  emphysema  induced  by  the  violent  res- 
piratorv  effort.  (2)  Increased  pulmonary  tension  induced  by  playing 
wind-instruments,  heavy  lifting,  etc.  The  studies  of  Prettin  and  Leib- 
kind  of  the  thoracic  condition  in  glass-blowers,  and  Fischer's  examination 
of  musicians,  have  cast  discredit  upon  the  previously  accepted  belief 
that  such  vocations  are  •  important  factors  in  the  production  of  em- 
physema. Collingwood's  conclusions  are  that  in  the  protected  parts 
of  the  lungs  the  condition  is  induced  by  causes  that  are  operative  dur- 
ing inspiration,  and  in  the  unprotected  areas — particularly  the  anterior 
margins  and  apex — the  emphysema  results  from  the  heightened  tension 
of  exaggerated  expiratory  effort. 

Morbid  Anatomy. — In  typical  cases  the  chest  is  barrel-shaped,  the 
most  conspicuous  alteration  being  an  increase  in  the  anteroposterior 
diameter.  The  sternum  is  pushed  forward  and  the  normal  obHquity  of 
the  ribs  greatly  lessened.  The  neart  is  lower  than  normal,  and  the 
diaphragm  depressed,  resulting  in  abdominal  displacement  of  the  sub- 
diaphragmatic viscera,  particularly  the  Hver  and  spleen.  The  costal 
cartilages  are  unusually  rigid  and  frequently  calcified ;  when  the  sternum 
is  raised,  the  lung  does  not  show  the  normal  tendency  to  collapse — 
indeed,  it  mav  not  retract  at  all,  and  may  bulge  forward.  The  anterior 
margin  of  the  lungs  extends  over  the  pericardium  to  a  varying  degree ; 
when  removed,  thev  do  not  collapse;  the  pleura  over  the  affected 
area  is  pale,  anemic,' dry,  and  the  unaffected  areas  are  congested;  white 
patches  occur  on  the  pleura — the  pulmonary  albinism  of  Virchow.  The 
emphvsematous  lines  may  follow  the  intercostal  spaces,  but  the  dis- 
ease is  most  marked  along  the  anterior  margins,  at  the  apex,  and,  less 
commonly,  around  the  margin  at  the  base.  Large  bullae  may  be  seen 
under  the  pleura,  varying  in  size  up  to  0.5  or  i  cm.,  and  at  the  free 
margin  they  may  attain  a  diameter  of  2  cm.  or  more.  Where  the  emphy- 
sema is  most  marked,  the  lung   fails  to  crepitate.     The  absence  of  elas- 


ORGANS  OF   KKSIMRATloN. 


59' 


ticity  is  imlicated  by  the  fatt  tliat  ])its  are  ()l)tainc<l  almost  as  readily  as 
in  edema,  althouj^h  edema  is  usually  absent.  In  unromj)lic-ated  cases  the 
weight  is  notably  less  than  nonnal.  The  color  depends  upon  the  amount 
of  pigment.  Usually,  the  organs  are  pale  and  any  residual  pigment  is 
conspicuous.  As  a  rule,  the  pulmonary  parenchyma  contains  less  blood 
than  normal;  and  even  when  death  has  been  delayed,  markefl  congestion 
and  consi)icuous  edema  are  freijucntly  absent.  The  lung,  when  handled, 
feels  like  a  pillow  stuffed  with  down  (Laennec).  The  smaller  bronchi 
may  be  tlilated;  more  or  less  bronchitis  and  peribronchial  induration 
are  always  present.  The  longitudinal  bands  of  elastic  tissue  may  be 
traceable  in  the  bronchial  wall.     (See  Fig.   29,^,  p.  592.) 

Morbid  Hi.stoloi^y. — If  the  lung  be  blown  up  and  dried,  the  enor- 
mous size  of  the  distended  vesicles  are  rendered  apparent;  even  on  sec- 
tion in  the  recent  state,  the  atrophic  remains  of  the  vesicular  walls  may 
be  discernible  with  a  hand  lens.  Hardened  and  examined,  the  elastic 
tissue  is  altered  in  quantity  and  quality,  and  the  vesicular  septa  atro- 
phied, permitting  coales- 
cence of  adjoining  cells;  in 
the  process  of  atrophy  the 
capillaries  disappear,  and 
this,  with  the  loss  in  septa, 
diminishes  the  aerating 
capacity  of  the  lung.  The 
most  conspicuous  changes 
\vill  be  observed  in  the 
elastica.  In  the  largest 
blebs  a  few  granules  of  this 
substance  are  scattered 
through  the  wasted  walls; 
in  other  areas  the  elastic 
fibers  are  coarse,  frag- 
mented, swollen,  and  fre- 
quently show  none  of  the 
undulations  present  in 
normal  elastic  tissue. 

Changes  in  Other  Or- 
gans.— The  increased  work  demanded  of  the  right  heart  in  emphysema 
leads  to  hvpertrophy  and  dilatation,  the  former  in  rare  cases  affecting 
the  entire  heart;  sclerotic  changes  in  the  pulmonary  artery  with  or 
without  dilatation  may  occur.  Other  organs — particularly  the  liver, 
spleen,  and  kidney — subject  to  the  alterations  of  structure  incident 
to  venous  distention  usually  manifest  that  change. 

Atrophic  or  senile  emphysema  {senile  atrophy  of  the  lung,  small- 
lunged  entphysenia  of  Jenner)  is,  as  its  name  indicates,  a  disease  of  ad- 
vanced life,  and  is  essentially  an  atrophic  lesion  of  a  lung  in  which 
vers'  little,  if  any,  distending  force  has  been  exerted.  The  chest  is 
small,  the  ribs  are  oblique,  thus  decreasing  the  diameters  and  dimin- 
ishing the  capacity  of  the  chest;  the  respiratory  muscles  are  atrophie<l 
and  the  lung  is  smaller  than  normal;  the  changes  in  the  vesicles  and 
septa  alreadv  noted  in  substantive  emphysema  occur.  The  enlargement 
in  the  size  of  the  vesicles  is  attributed  to  atrophy  of  the  inters'esicular 
walls.     The  bronchi  frequently  show  some  dilatati^v-      1  .r-.r..  K-jUae  are 


FiC.  J92. — PfLMOSARV    KUPHYSEM.X. — (Flullfrfr.) 

Kmphyscmatous  enlargement  of  an  infundihulum.  h.  .\tro- 
phied  intcn-esicular  septa,  improperly  called  absorbed  alveolar 
walls,    c.  Pigment  in  the  fibrous  septum. 


592 


SPECIAL  PATHOLOGY. 


usually  absent;  the  lung  commonly  collapses  on  opening  the  chest, 
and,  in  contrast  with  large-lunged  emphysema,  not  infrequently  shows 
areas  of  congestion,  edema,  and  infarction.  There  may  be  some  doubt 
as  to  the  propriety  of  classifying  this  condition  with  emphysema.  The 
fact  that  custom  has  established  the  precedent  does  not,  of  course, 
prove  its  correctness.  A  better  knowledge  of  atrophy,  occurring  in  the 
lung,  would  probably  lead  to  the  recognition  in  this  form  of  emphy- 
sema of  some  atrophic  manifestation  analogous  to  that  seen  in  other 
tissues  in  advanced  life. 

Acute  vesicular  emphysema  is  observed  in  acute  bronchitis  and 
after  death  from  asphyxia;  there  is  also  reason  to  believe  that  vesic- 
ular distention  is  present  during  Hfe  in  these  cases.     That  the  condi- 


FiG.  293. — Lung,  Emphysema. 
Weigert's  elastica  stain.     Fragmentation  and  swelling  of  the  elastica. 

tion  is  unassociated  with  atrophy  of  the  vesicular  walls  is  admitted. 
In  the  absence  of  such  atrophy  it  consists  largely  of  functional  over- 
distention,  and  is  not  properly  a  disease  of  the  air-vesicles. 

Pulmonary  Suppuration,i  Including  Abscess  of  the  Lung.— This  con- 
dition is  commonly  described  under  the  head  of  purulent  pneumonia, 
suppuration  pneumonia,  etc.,  names  indicating  that  it  is  some  special 
type  of  pulmonarv  disease  rather  than  the  usual  form  of  suppurative 
lesion.  Etiologically  and  pathologically,  and  to  a  certain  extent  cHnic- 
ally,  suppurative  processes  occurring  in  the  lung  possess  no  important 
difference  from  suppurations  arising  from  pyogenic  infection  in  other 
organs. 

>Eisendrath.  "Phila.  Med.  Jotir.,"  Nov.  9,  1901.  Bentz,  "La  Presse  Med.," 
1902,  No.  97.     Jurewitsch,  "Mtinch.  med.  Woch.,"  March  15,  1904,  p.  480. 


OKGANS   UK   KKSPIRATION. 


593 


Pnniarv  pulmonary  sui.i)uration  is  an  exceedingly  rare  condition; 
pyogenic  infection  may  be  brought  to  the  lung  in  one  of  four  ways: 
(A)  Hy  the  air-passages;  (i!)  from  loiiliguoiis  striuluns:  (C)  by  the 
blood;     (D)  by  the  lymphatics. 

{A)  By  the  Air-passages  {Hronchogenie  Sitppiiratioii).-- Although  we 
are  constantly  inhaling  large  numbers  of  bacteria,  many  of  them  un- 
doubtedly pyogenic,  and  in  other  ways  pathogenic,  the  bactericidal 
action  of  the  extruded  einthelium,  leukocytes,  mucus,  serum,  etc.,  pre- 
vents ingress  or  pathogenic  activity  except  the  tissues  be  weakened 
by  (i)  ge)ieral  debility,  (2)  previoits  local  disease,  or  (3)  accompanying 
injury.  As  examples  of  these  may  be  mentioned:  of  the  first,  the 
probability  that  tibrinous  pneumonia  in  drunkards  will  present  a  mixed 
infection;  of  the  second,  pyogenic  infection  of  tuberculous  areas,  or 
of  the  areas  involved  in  lobar  or  lobular  pneumonia,  or  in  pneumo- 
coniosis. In  lobar  pneumonia  abscess  formation  is  rare;  the  so-called 
purulent  infiltration  is  not  really  pus,  as  it  not  uncommonly  contains 
no  pneumococci,  and  rarely,  if  ever,  are  the  bacteria  of  suppuration 
present.  If  abscess  formation  takes  place  in  pneumonia,  it  usually 
begins  as  scattered  foci  of  infection,  and,  as  such,  is  found  ])Ostmortem; 
rarely,  however,  these  foci  extend  and  run  together,  the  infection  lessen- 
ing or  obliterating  the  circulation  in  the  area,  and  more  or  less  of  a 
lobe  may  be  converted  into  an  abscess.  Abscess  formation  in  acute 
lobular  pneumonia  is  still  rarer. 

Suppuration  from  injtiry  ivith  injection.  Exploratory  puncture  of 
the  pleura  has  caused  pulmonary  abscess.  But  the  form  of  suppuration 
due  to  an  injury  which  brings  infection  with  the  trauma,  and  both 
through  the  air-passages,  is  typified  in  the  so-called  aspiration  pneumonia. 
Foreign  bodies  in  the  air-passages;  suppurative  processes  in  or  around 
the  larynx,  trachea,  or  larger  bronchi;  deglutition  pneumonia,  in  which, 
from  altered  innervation,  food  particles  gain  ingress  to  the  air-passages; 
and  allied  processes,  all  may  give  rise  to  abscess  formation  bv  deposit- 
ing an  irritant,  no  matter  how  small,  and  with  it  the  bacteria  of  sup- 
puration. Bronchogenic  pyogenous  infection  induces  suppurative  in- 
flammation of  the  bronchi  which  extends  into  the  contiguous  vesicles 
and  interstitial  tissue.  Polymorphonuclear  leukocytes  accumulate  in 
large  numbers,  necrosis  of  the  involved  pulmonary  structures  occurs, 
and  an  abscess  results.  Commonly  such  suppurative  processes  are 
primarily  restricted  to  lobules;  frequently  they  are  multiple,  and  coal- 
escing with  contiguous  areas,  may  give  rise  to  abscesses  of  considerable 
size. 

{B)  Pulmonary  suppuration  arising  through  extension  of  the  infec- 
tion jrom  contiguous  structures  is  not  common,  in  the  sense  that  the 
abscess  extends  by  necrosis  of  the  lung  tissue;  but  in  the  lymphatics 
such  extension  may  occur.  Localized  or  circumscribed  empyema,  or 
pleural  abscess,  particularly  when  situated  between  the  lobes  or  at 
the  base,  between  the  diai)hragm  and  lung,  may  penetrate  tlie  pulmon- 
ary tissue  by  a  gradually  extending  necrosis,  and  eventually  may  find 
evacuation  through  a  bronchus.  Abscess  of  the  liver  or  suppurating 
echinococcus  may  perforate  the  diaphragm  and  infect  the  lung;  Hentz 
records  an  instance  in  which  a  tuberculous  abscess  of  the  right  iliac 
fossa  communicated  with  a  bronchus.  Mediastinal  abscess  and  other 
fonns  of  peripulmonic  suppuration  may  likewise  induce  suppurative 
39 


594 


SPECIAL  PATHOLOGY. 


pulmonic  lesions.     Cancer  of  the  esophagus  may  lead  to  direct  infec- 
tion of  the  lung  tissue  or  of  the  air-passages. 

(C")  Pnbnonary  suppuration  from  injection  through  the  blood  {hemato- 
genous infection)  was  the  common  sequence  of  preantiseptic  surgery  and 
obstetrics.  Emboli  containing  the  cocci  of  suppuration  lodge  in  the 
lung  and  give  rise  to  centers  of  infection,  followed  by  abscess  formation. 
These  abscesses  are  small,  usually  multiple,  superficially  located,  not 
uncommonly  cone-shaped,  with  the  base  of  the  cone  toward  the  pleura, 
into  which  they  not  infrequently  rupture,  giving  rise  to  suppurative 
pleurisy  (empyema  or  pyothorax),  or,  if  communication  has  been  es- 
tablished between  the  abscess  cavity  and  a  bronchus,  thereby  admit- 
ting air  to  the  pleural  cavity,  there  quickly  results  a  pyopneumothorax. 
(See  Metastatic  Abscesses,  p.  284.) 

{D)  Infection  of  the  Pulmonary  Structure  through  the  Lymph-channels 
{Lymphogenic  Infection). — An  interstitial,  peribronchial,  or  interlobular 
suppurative  process  may  result  from  invasion  of  the  lung  tissue  by 
wav  of  the  peribronchial  lymphatics.     Thus,  in  suppurative  inflamma- 
tion of    the    pleura  (empyema)  the    lymphatics    passing   through   the 
lung  may  be  distended  by  infective  material,  or  exudates  eminently 
adapted  to  infection,  and  cocci  accompanying  the  process  or  gaining 
ingress  to  the  resulting  lesion,  may  give  rise  to  pus  formation  in  the 
interstices  of  the  lung;    as  the  infection  is  in  the  lymphatics  around 
the  bronchi,  it  is  spoken  of  as  peribronchial   suppurative  lymphangitis. 
The  condition  can  not  be  diagnosticated  during  life,  and  is  recognized 
only  postmortem.     Pyogenic  agents  reaching  the  lung  or  its  lymphatic 
system  from  the  mediastinum  or  elsewhere  may  give  rise  to  the  process. 
Morbid  Anatomy  of  Pulmonary  Abscess. — When  solitary,  the  abscess 
may  attain  the  size  of  a  lobe;    when  multiple,  they  are  usually  small. 
The  contents,  in  addition  to  pus,  contains  epithelial  debris  and  rem- 
nants of  lung  tissue,  the  demonstration  of  which  in  the  sputum  is  a 
valuable  aid  to  diagnosis.     If  evacuation  has  occurred  during  Hfe,  the 
walls  may  be  gangrenous  and  the  cavity  exceedingly  fetid ;    if  the  mass 
be  small  and  the  patient  in  good  condition,  a  fibroid  protecting  wall 
may  form;     ordinarily,  however,  the  wall  is  formed,  from  within  out- 
ward, by  a  layer  of  (i)  necrotic  disintegrating  lung  and  inflammatory 
tissue;     (2)  a' layer  of  soHdified  lung  infiltrated  with  leukocytes  and 
young  connective-tissue  cells,  and  commonly  containing  hemorrhages 
in  the  alveoli  and  interstitial  tissue;  (3)  edematous  lung  tissue.     If  the 
pleura  has  not  been  opened,  the  abscess  wall,  formed  by  that  structure, 
is  covered  by  an  abundant  exudate  of  fibrin,  and  some  cloudy  serum, 
varying  in  quantity,  will  probably  occupy  the  cavity.     Purulent  pleurisy 
(empyema)  may  occur  without  rupture  of  the  abscess,  but  invariably 
results  if  rupture  takes  place,  and  is  usually  accompanied  by  pneumo- 
thorax, the  latter  depending  upon  whether  the  abscess  communicates 
with  an  open  bronchus.     Rarely,  a  pulmonary  abscess  may  encapsulate, 
as  previously  indicated;     in  lobar  pneumonia,  when  the  evacuation  is 
complete,   cicatrization  has  been  known  to  occur;     the  same  change 
has  been  observed  in  hepatic   abscess   discharging  through  the  lung. 
The  majority  of  cases  terminate  fatally.     Sometimes  infection  is  wide- 
spread and  is  not  associated  with  distinct  abscess  formation.     Under 
these  circumstances  the  condition  is  one  of  peribronchial  suppurative 
lymphangitis,  mentioned  above. 


ORGANS   OI-    KKSPIKATIOX. 


595 


Attempts  have  been  made  to  classify  jjulmonary  abscesses  ac-cord- 
ing  to  the  cause,  as,  pyogenic,  tuberculous,  actinomycotic,  pneumonic, 
etc.  But  these  processes,  when  terminating  in  pus  formation,  are 
essentially  mixed  infections  in  the  vast  majority  of  cases,  and  the 
primary  disease  does  not  materially  alter  the  true  character  of  the 
developed  malady. 

Gangrene  of  the  lung'  consists  of  two  factors:  (i)  Death  of  a  part 
of  tile  puinioiiarx-  tissue  (necrosis)  or  a  material  lessening  of  its  biood 
.supply  and  (2)  infection,  which  must,  in  all  probability,  be  ])olymicrobic. 
Infection  alone  often  fails  to  produce  this  form  of  necrosis;  oblitera- 
tion of  the  blood  supply  does  not  insure  gangrene;  the  lung  tissue  must 
be  killed,  or  its  resistance  to  bacteria  greatly  reduced,  and  coincident, 
or  subsequent,  infection  then  completes  the  process.  If  pyogenic  infec- 
tion occur  in  a  lung  the  blood  supply  of  which  is  abundant,  supjmration 
is  induced,  pus  being  a  product  of  vital  reaction  to  pyogenic  mvcotic  in- 
vasion: if.  however,  the  tissue  be  dead,  if  vital  ])rocesses  be  materiallv 
weakened,  the  tissue  resistance  reduced,  the  nutrition  greatlv  modified 
by  existing  lesions,  or,  it  may  be.  arrested,  the  pyococci  and  associated 
organisms  give  rise  to  gangrene. 

The  causes  of  pidnioiiary  ,{,'a;;t,';r;/t',  then;  embrace  all  those  condi- 
tions that  materially  lessen  or  arrest  nutrition  and  permit  infection — 
lobar  pneumonia,  aspiration  pneumonia,  foreign  bodies  in  the  bronchi, 
pulmonary  embolism,  bronchiectasis,  suppurative  conditions  in  the  lung, 
pressure,  as  from  tumors  and  aneurysms  on  the  bronchi  and  blood- 
vessels, etc.  The  cases  of  pulmonary  gangrene  that  accompanv,  or, 
more  commonly,  follow,  severe  febrile  processes  are  probablv  infections 
in  areas  of  hypostatic  or  hemorrhagic  pneumonia.  Brain  abscess  and 
middle-ear.  and  mastoid  disease,  by  infectious  thrombosis  of  the  sinuses, 
frequently  induce  pulmonary  embolism,  which,  being  infected,  is  often 
followed  by  gangrene  or  abscess.  The  same  is  true  of  infectious  pro- 
cesses in  the  venous  system  elsewhere.  The  bacteriologv  of  pul- 
monary gangrene  has  been  studied  by  a  number  of  observers;  the 
results  have  been  collated  by  Ophiils,  who  adds  five  personal  obser- 
vations. In  many  of  the  cases  acid-fast  bacilli  and  organisms  resembling 
the  streptothrix  group  are  present.  The  germs  possessing  the  characters 
of  tubercle  bacilli  may  mislead  the  uninitiated,  but  are  usuallv  easilv 
recognized  by  experienced  observers.  Rosenberger-  has  shown  that 
within  certain  limits  it  is  possible  to  differentiate  a  number  of  these 
organisms.     Anaerobic  bacteria  are  usually  present. 

Morbid  A>iiitoniy. — Two  forms  are  recognized:  the  diffuse  or  dis- 
seminated and  the  circmuscrihed.  The  division  made,  independent  of 
any  surgical  conce[)tion  of  the  affection,  seems  well  adapted  to  the 
modern  surgical  divisions  of  gangrene —circumscribed  and  sjireading. 
Clinicians  recognize  a  latent  pulmonary  gangrene  characterized  by  the 
absence  of  the  usual  symptoms,  notably 'the  offensive  odor  of  the  breath 
and  the  fetid  expectoration.  In  some  of  the  latent  cases  the  area  in- 
volved is  large  and  may  be  multiple. 

'  Withincrton.    "Boston    Med.    and    Surj;.   Jour,      .March    10,    i.s^.s.     (iphul.s. 
■Jour,  of  Med.   Research."  June.    IQ02,  vol.   viii.  p.   242.      Holzle.   Inauj;.    Diss.. 
Munich,  No.    136.   1Q03.     Steven.    'Lancet,"  Oct.   15.   i()04,  p.   1077.      Budinjjer, 
'Munch,  med.  Woch."  Oct.  18.  1904,  p.  1874.     Anders  and  McFarland,  "Medi- 
cine."   Feb.,    igo2. 

'  Publications  from  the  Laboratories  of  the  Jefferson  Medical  College  Hospital, 
1904,  vol.  i. 


596 


SPECIAL  PATHOLOGY. 


Diffuse  pulmonary  gangrene,  like  the  spreading  form  of  the  surgical 
affection,  is  rare,  and  commonly  fohows  pneumonia,  and,  although 
less  frequently,  obstruction  of  the  pulmonary  artery.  There  is  not  a 
sharp  line  of  demarcation  between  the  healthy  and  diseased  tissue ;_  a 
whole  lobe,  or  the  greater  part  of  a  lobe,  is  involved,  the  process  being 
well  marked  at  the  center  of  the  diseased  area,  but  gradually  fading 
into  the  surrounding  zone  of  highly  inflamed  pulmonary  tissue. 

In  the  circumscribed  pulmonary  gangrene  there  is  a  sharp  line  of 
demarcation  between  the  dead  and  the  inflamed  tissue,  and,  although 
the  foci  mav  be  multiple,  each    area   involved   is  clearly  outlined  in 

the  living  pulmonary 
structure. 

The  gangrenous 
mass  in  either  case  is. 
as  a  rule,  extremely 
fetid,  and  during  life 
this  foul  penetrating 
odor  is  imparted  to  the 
breath,  and  persists  for 
hours  in  the  sputum. 
The  latter,  when  left  in 
a  conic  glass,  usually 
manifests  a  tendency  to 
separate  into  three 
layers:  the  uppermost 
is  thick,  frothy,  yellow 
or  green  or  greenish- 
V  el  low  in  color;  the 
middle  stratum  is  a 
clear  serous  fluid,  but 
slightly  tinted;  the  sed- 
iment is  greenish-brown, 
occasionally  pus -like, 
and  contains  the  char- 
acteristic odor  in  its 
fullest  concentration. 
Elastic  fibers  are  not 
always  present,  al- 
though they  usually  are 
to  be  found;  Eijkman^ 
has  shown  that  certain 
bacteria  evolve  an  elas- 
tica-dissolving  enzyme,  and  it  is  possible  that  the  disappearance  of  elastic 
tissue  in  pulmonary  gangrene  may  be  attributable  to  the  action  of  some 
such  substance.  The  color  of  the  diseased  tissue  is  dependent  upon  the 
stage  and,  probably  to  a  large  extent,  upon  the  character  of  the  infection. 
Early,  it  is  brown  or  reddish  brown;  and  later,  quite  black.  The  color- 
changes  are  in  part  brought  about  by  the  presence  of  blood  pigment,  to 
which  the  brownish  hue  is  to  be  attributed.  The  blackening  is  partly 
due  to  changes  in  the  hemal  iron  as  well  as  to  the  presence  of  iron-free 
pigment.  The  occasional  greenish  hue,  which  may  be  marked,  is 
1  "Centralbl.  f.  Bakt.,"  Nov.  5,  1903,  p.  1. 


Fig.  294. — Part  of  Right  Lung,  Circumscribed  Gangrene. 
A .  Two  pockets  of  gangrenous  cavity.    B.  Dilated  bronchus  \^^th  gan- 
grenous walls.     C,C.    Solidified  zone  of   pulmonary  inflammation. 
D.  Adhesion  between  superior  and  inferior  lobes.    E.  Beginning 
abscess  at  margin  of  gangrenous  area. 


OKC.ANS   Ol'   RFSPIkATKJN.  597 

due  to  changes  in  normal  pigments  or  to  the  i)resence  of  the  bacillus 
pyocvaneus.  In  the  earlier  stages  the  gangrenous  tissue  may  retain 
its  structure,  but  disintegration  rapidly  ensues,  and  a  cavity  with  ragged 
irregular  walls  forms,  inclosing  a  green  or  reddish-yellow  mass  of  soft- 
ened necrotic  tissue.  Passing  into,  often  across,  the  cavity  are  remains 
of  blood-vessels  and  bronchi.  By  reason  of  the  infectious  character 
of  the  lesion,  the  blood-vessels  are  not  occluded,  as  normally,  by  an 
organizing  thrombus;  the  coagulum  forming  in  the  lumen  being  infected, 
is  easily  displaced,  permitting  hemorrhage,  which  may  be  recurrent, 
and  in  rare  cases  fatal.  Around  the  gangrenous  area  there  is  a  zone 
of  deeply  congested  or  intensely  hyperemic  tissue,  which  is  usually 
solidified,  and  outside  of  this  an  area  of  marked  edema  with  leukocytic 
infiltration.  Cicatrization  and  recovery  may  occur;  the  disease  is  more 
commonly  fatal. 

Pneumonia. 

The  term  pneumonia  is  used  to  embrace  all  the  inflammatory  lesions 
of  the  pulmonary  tissue,  often  including  some  of  the  processes  already 
considered;  for  example,  pulmonary  suppuration  is  sometimes  spoken 
of  as  septic  pneumonia  or  suppuration  pneumonia.  When  the  term 
pneumonia  is  used  alone,  without  any  qualifying  phrase,  croupous 
pneumonia  is  usually  meant.  The  forms  of  pneumonia  commonly  con- 
sidered are  lobar  or  croupous  pnctimonia,  catarrhal  pneumonia,  or  hron- 
chopncumonia,  interstitial  or  fibroid  pneumonia,  and,  by  some  writers, 
the  desquamative  pneumonia  of  tuberculosis. 

Lobar,  Croupous,  or  Fibrinous  Pneumonia*  {Pneumonitis;  Luuf: 
Freer). — The  fact  that  the  pleura  is  usually  involved  has  led  to  the 
name  pleuropneumonia.  This  disease  is  an  acute  inflammatory  affection 
of  the  lung  due  to  infection. 

'  Xorris,  "Amer.  Jour,  of  Med.  Sci.,"  June.  1901.  Blumer,  "Albany  Med 
Annals,"  Aug..  1901.  Fisher,  "Amer.  Jour,  of  Med.  Sci.,"  Aug.,  1901.  Fouler- 
ton,  "Lancet,"  Aug.  17,  igoi.  Busquet.  "Revue  de  Med.."  Feb.  10,  1902.  Burt. 
"Amer.  Med.,"  April  26,  1902.  Littleiohn,  "  EdinVjurgh  Med.  Jour.."  April. 
1902.  Maschke,  "Cleveland  Med.  Jour.,"  May,  1902.  Sears  and  Larrabee, 
"Med.  and  Surg.  Reports  of  Boston  City  Hosp.,"  twelfth  series,  Dec.  i,  1901; 
also  "St.  Paul  Med.  [our.."  July,  1902.  Hare  and  Dare,  "Med.  News."  Aug.  33 
and  30.  1902.  Hans  "Kohn,  "Berl.  klin.  Woch.."Noy.,  1903.  Spitta,  "Brit.  Med. 
lour.,"  Nov.  15,  1902,  p.  1579.  Washboum,  Croonian  Lectures  for  1902;  "Lan- 
cet." 1902,  vol.  ii.  Wadsworth,  "Amer.  Jour,  of  Med.  Sci.,"  May.  1904-  Eb- 
stein,"Munch.  mcd.  Woch.."  May  5,  1903.  p.  761.  Rosenow,  "Jour,  of  Infectious 
Diseases,"  March  19,  1904,  p.  280^  also  "Jour.  Amer.  Med.  Assoc,"  March  18, 
1905.  Kerr,  "Trans,  of  Chicago  Path.  Soc,"  May  11  and  June  S.  1903.  Tcbisto- 
vitch,  "Annals  de  I'lnst.  Pasteur,"  May  2s,  1904.  Goss,  "Arch,  des  Sc.  Biol, 
de  St.  Petersburg,"  1904.  No.  5,  p.  429.  Durck,  "Miinch.  med.  Woch.."  June 
28,  1904,  p.  1137.  Callender,  "Brit.  Med.  Jour.,"  July  16,  1904.  p.  116.  Koawa. 
"Berl.  klin.  Woch.."  1904.  No.  14.  Stuertz,  "Zeit.  f.  klin.  Mcd.,"  1904,  Bd. 
lii,  p.  422.  Rau,  "Zeit.  f.  Heilkunde."  1904.  H.  i.  Tarchetti  and  Curio.  "Gazz. 
degli  Osped.  e  delle  Clin.,"  1904,  March  27,  p.  3S7.  Manges.  "Med.  Record." 
Dec.  10.  1904.  p.  929.  Wells.  "Jour.  Amer.  Med.  Assoc."  Sept.  24.  1904.  Morse. 
"Amer.  Med.."  Ian.  28.  1905.  p.  153.  Heyman.  "Tht^'se  de  Wurtsbourg."  1Q04. 
Bottomley,  "Brit.  Med.  Jour'.  Feb.  4.  1905.  p.  237.  WoUstcin.  "Jour,  of  Fi.vper. 
Med.."  1905,  vol.  vi,  Nos.  4,  5,  and  6,  p.  391.  Ramsdell.  "Amer.  Mcd.."  Feb. 
II.  1905,  p.  237.  Kiefler.  "Amer.  Med.,"  March  4,  iqos.  p.  356.  Pratt. 
Contributions  to  the  Science  of  Medicine  by  the  Pupils  of  William  H.  Welch. 
1900.   pp.    265  to  277. 


598 


SPECIAL   PATHOLOGY 


That  pneumonia  is  a  disease  due  to  bacterial  invasion  is  now  uni- 
versally admitted.  That  it  is,  however,  the  result  of  a  single  organism 
seems  no  longer  probable,  although  not  absolutely  disproved.  The 
germ  most  frequently  present  is  the  Diplococcus  pneumoniae, ^  which 
was  described  by  Sternberg  as  the  micrococcus  of  rabbit  septicemia, 
and  named  by  him  the  micrococcus  of  Pasteur.  This  organism  was 
later  studied  by  a  number  of  observers,  and  was  found  by  Frankel  and 
Talamon  in  the  lung  in  croupous  pneumonia;  it  is  sometimes  called 
the  pneumococcus  of  Frankel. 

In  1882  Friedlander  described  an  organism-  associated  with  pneu- 
monia, to  which  he  gave  the  name  pneumococcus.  As  a  result  of  later 
studies  the  germ  is  now  held  to  be  a  bacillus.  Croupous  pneumonia 
clinically    and   anatomically    not   to   be    differentiated    from    croupous 

pneumonia  produced  .by  the  pneu- 
mococcus of  Frankel  may  result 
from  infection  by  streptococci,  and 
possibly  staphylococci,  although  it  is 
usually  held  that  the  presence  of  the 
latter  organism  is  to  be  attributed  to 
a  mixed  or  secondary  infection,  and 
that,  even  when  found  alone,  the 
primary  pneumonia  was  due  to  the 
pneumococcus  or  other  bacterium 
which  has  disappeared.  The  Bacillus 
typhosus,  Bacillus  influenzae,  colon 
bacillus,  plague  bacillus,  and  possibly 
a  number  of  micro-organisms  may 
bring  about  that  form  of  solidification 
usually  regarded  anatomically  charac- 
teristic of  croupous  pneumonia.  The 
pneumococcus  is  present  in  from 
seventy -five  per  cent,  to  eighty  per 
cent,  of  the  cases  examined  postmor- 
tem. The  anatomic  distribution  of 
the  lesion  would  indicate  that  infec- 
tion usually  takes  place  through  the 
bronchi.  Atypical  distribution,  and 
occasionally  associated  lesions,  would 
lead  us  to  admit  the  possibility  of  primary  hematogenous  infection. 
Certain  predisposing  causes  are  recognized.  These  act  in  one  of 
two  ways:  (i)  By  altering  the  saliva,  and  thereby  the  culture  medium 
in  which  the  organism  is  growing;  these  changes  in  the  pabulum 
increase  the  virulence  of  the  pneumococcus;  (2)  the  predisposing  ele- 
ments so  weaken  the  tissues  that  infection  becomes  possible.  The 
latter  is  illustrated  by  the  frequency  with  which  pneumonia  occurs 
in  drunkards,  in  the  debilitated,  in  Bright's  disease,  and  after  contu- 
sions of  the  chest.  Of  the  two  hypotheses  it  seems  the  more  reason- 
able, and  but  little  importance  is  usually  attached  to  the  first  given. 

All  ages  are  Hable,  but  pneumonia  is  most  frequent  in  three  periods 
— early  childhood,  between  twenty  and  forty,  and  after  sixty.     It  is 

*  For  description  see  p.    109. 
2  For  description  see  p.    127. 


Fig.  295. — ^Sputom,  Croupous  Pneumonia. 
In  the  extreme  upper  part  of  field  is  a  leukocyte 
showing  chromatolysis  but  containing  en- 
globulated  cocci.  Below  and  slightly  to  the 
left  of  this  cell  is  a  squamous  cell  from  the 
mouth.  To  the  right  of  the  latter  and  slightly 
below  is  a  polymorphonuclear  leukocyte,  and  in 
the  extreme  lower  part  of  the  field  is  a  small 
iiyaUne  cell.  The  field  also  contains  numerous 
encapsulated  pneumococci,  a  few  streptococci, 
and  unarranged  cocci  that  can  not  be  accu- 
ratelv  identified. 


ORGAN'S  OF   RESPIRATION.  599 

more  common  among  males  than  females;  where  hc^th  are  subject  to 
the  same  influences,  there  is  little  ditTerence.  Of  Scars  and  Larrahee's 
949  cases,  714  were  males.  Comlitions  dislurl>ing  the  equilibrium  of 
the  pulmonary  circulation,  as  chronic  heart  disease,  retention  of  ex- 
crementitious  matters,  as  in  uremia, — in  other  words,  any  j^rocess  re- 
ducing the  vital  powers  and  enabling  infection  to  occur, — favor  the  de- 
velopment of  pneumonia.  Unhygienic  environment  acts  in  two  ways 
— (a)  bv  reducing  resistance  and  (/')  by  favoring  the  accumulation  of 
infectious  material  in  the  surroundings.  The  si)CciHc  cause  elucidates 
the  occasional  occurrence  of  epidemics  in  crowded  or  unhygienic  (quar- 
ters. That  unsanitarv  environment  is  not  necessary  to  the  production 
of  an  epidemic  is  shown  by  records  of  hospitals  and  institutions  where 
children  are  housed  in  large  numbers.  In  the  epidemic  of  pulmonary 
inflammations  observed  by  Spaet  13.9  per  cent,  of  the  population  suf- 
fered. It  has  been  shown  experimentally  that  exposure  to  cold  and 
dampness  increases  the  susceptibility  of  animals.  There  seems  to  be 
an  individual  predisposition,  as  manifested  by  the  frequent  recurrence 
of  pneumonia  in  the  same  individual,  twenty-eight  attacks  having 
been  observed  in  one  patient  (Loomis).  That  relapses  do  not  com- 
monlv  occur  seems  to  indicate  a  condition  of  acquired  immunity;  that 
such  is  of  brief  duration  is  also  presumable  from  the  susceptibility 
to  recurrent  attacks.  Experimentally,  it  has  been  shown,  in  animals, 
that  a  certain  degree  of  immunity  may  be  secured  by  the  injection  of  fil- 
tered bouillon  cultures  of  the  pneumococcus  or  a  glycerin  extract  pre- 
pared from  the  growing  organism.  The  immunity  is  temporary,  lasting 
but  a  few  months,  but  during  that  time  is  transmitted,  in  gestation 
and  bv  nursing,  to  the  offspring.  The  serum  of  such  animals  has  been 
used  with  beneficial  results  in  the  treatment  of  pneumonia. 

Morbid  Atuitoniy. — Pneumonia  involves,  as  a  rule,  either  a  whole 
lobe  or  a  whole  lung,  most  commonly  the  lower  right  lobe;  the  lower 
left  lobe  is  next  in  order;  third  in  point  of  frequency  is  double  pneu- 
monia, while  pure  croupous  pneumonia  of  the  apices  is  rare.  The 
right  apex  is  more  frequently  involved  than  the  left.  Kerr's  statistics 
show  that  the  affection  is  unilobar  in  forty-two  per  cent,  and  unilateral 
in  eightv-four  per  cent,  of  the  cases.  The  lesion  is  double  in  from 
twelve  to  fifteen  per  cent,  of  the  cases.  The  whole  of  the  affected 
lobe  or  lung  is  usually  in  the  same  stage,  although  wandering,  creep- 
ing, or  migratory  pneumonia,  involving  one  lobe  after  another,  shows 
different  stages  in  ditTcrent  lobes;  in  such  cases  the  lower  lobe  is 
most  frequently  first  involved.  In  rare  instances  one  lobe  and  part 
of  another  may  be  affected,  and  in  different  stages.  Occasionally, 
central  changes  precede  peripheral  lesions,  and  the  center  of  the  lung 
is  grav,  while  the  periphery  is  less  advanced — central  pneumonia ; 
rarely,  the  reverse  may  be  demonstrated.  In  <louble  pneumonia  one 
lung  mav  be  further  advanced  than  the  opposite  organ.  In  infancy 
and  in  old  age  the  apex  is  more  frequently  the  initial  point  of  invasion; 
in  the  aged,  death  occurs  earlier  in  the  attack  than  in  the  adult.  When 
the  disease  is  one-sided,  the  unaffected  lung  is  commonly  deeply  hy- 
peremia and  congested. 

For  purposes  of  description  it  is  customary  to  recognize  three  stages, 
called  (i)  engorgement.  (2)  red  hepatization.  (3)  gray  hepatization. 
Pratt's  studies  show  that  the  differences  between  the  n-d  .m.l  tho  gray 


6oO  SPECIAL  PATHOLOGY. 

hepatization  can  not  be  detected  histologically;  in  other  words,  that 
the  color  upon  which  the  differentiation  rests  is  not  characterized  by 
a  constant  histologic  picture. 

State  of  Engorgement. — When  the  chest  is  opened,  the  lung  does 
not  retract  or  collapse  with  its  wonted  rapidity;  there  may  be  a  slight 
shrinking  in  volume,  but  the  general  contour  of  the  organ  is  likely  to 
be  retained.  The  lung,  or  the  area  involved,  is  red,  often  a  scarlet 
hue.  Crepitation  is  present  throughout,  but  is  less  distinct  than  nor- 
mal; the  specific  gravity  is  greater  than  in  health,  as  is  shown  by  the 
fact  that  while  the  lung  floats,  it  does  not  float  as  high  as  the  normal 
organ.  Occasionally,  the  pleura  shows  evidence  of  beginning  inflam- 
mation. (See  p.  476.)  On  section,  the  color  is  uniform;  as  a  rule, 
blood  oozes  from  the  cut  surface,  and  while  in  the  majority  of  the 
cases  the  blood  is  thick,  flowing  slowly,  in  some  cases  an  abundant 
transudate  of  serum  appears  immediately  on  section,  which,  mixing 
with  the  blood,  bathes  the  incised  surface,  and  drips,  or  even  runs, 
from  the  dependent  edge.  On  microscopic  examination  the  capillaries 
of  the  vesicular  walls  are  found  enormously  distended,  tortuous,  and^ 
even  saccular;  the  epithelium  of  the  vesicles  is  swollen  and,  in  places, 
desquamating;  in  the  few  vesicles  with  marked  desquamation  some 
leukocytes  and  red  blood-corpuscles  may  be  demonstrated.  The  sub- 
pleural  and  interlobular  connective  tissue  also  shows  the  engorgement, 
and  the  lobules  may  be  outlined  under  the  pleura  by  the  intensely 
distended  vessels. 

This  stage  lasts  from  a  few  hours  to  two  or  three  days;  rarely  the 
latter.  It  seems  reasonable  to  suppose  that  in  the  last  moments  of 
life,  or  even  after  death,  solidification  may  occur,  or,  having  already 
developed,  may  extend.  Thus,  the  author  has  made  postmortems  after 
the  most  experienced  clinicians  had,  but  a  few  moments  before  death, 
outHned  the  area  that  seemed  solid;  in  not  a  few  of  these  cases  has 
the  solidification  been  found  far  beyond  the  outlines  indicated  by  the 
physical  examination  made  just  before  death.  This  offers  some  con- 
solation for  undiagnosticated  areas  of  soHdification,  but  it  is  also  ex- 
plained by  assuming  that,  after  death,  the  lung  rises,  as  a  result  of 
retraction  or  partial  atelectasis  of  the  unsolidified  areas  above.  Death 
rarely  occurs  in  this  stage  except  when  great  exposure,  an  alcoholic 
debauch,  or  other  debilitating  antecedent  conditions  are  incident  to 
the  attack. 

The  stage  of  engorgement  is  often  found  in  one  part  of  the  lung 
when  another  area  is  more  advanced,  or  in  one  lung  when  its  fellow 
is  solidified.  It  seems  reasonable  to  assume  that,  in  very  rare  cases, 
recovery  may  occur  without  further  progress  of  the  morbid  process. 

Stage  of  Red  Hepatization. — The  stage  of  engorgement  terminates 
by  the  distended  blood-vessels  pouring  out  an  inflammatory  exudate 
into  the  air-vesicles,  and  thus,  by  excluding  the  air,  bringing  about 
the  stage  of  solidification.  The  lung,  or  affected  area,  on  opening  the 
chest,  shows  absolutely  no  tendency  to  retract;  it  is  voluminous,  and 
may  be  marked  by  the  ribs;  the  color  is  darker  than  in  the  first  stage,  or 
rather  more  of  a  brown  or  reddish-brown;  the  area  involved  is  solid, 
and  the  absence  of  air  is  shown  in  the  entire  freedom  from  crepitation, 
in  the  absolute  dullness,  great  weight,  and,  when  thrown  into  water, 
the   rapiditv   with   which   the   part   involved   sinks.     On   section    (see 


Pl.ATH    VII. 


Lung.     ('r<>u|x)U>  Pnrumonia.     Stage  of  red  hepatization. 
{Fox's  Alias.) 


ORGANS  Ol-    RKSPIKATI(J\. 


60  I 


Plate  VII),  the  orj^^an  is  dry,  rough,  and  granular;  a  finger  passed  over 
the  scraped  surf-ace  gives  to  the  observer  the  imi)ression  of  a  rough 
surface,  not  unlike  ground  glass;  this  and  the  granular  appearance 
are  due  to  the  plugs  of  lihrin  that  occlude  the  vesicles  and  on  section 
project;  they  may  be  scraped  out  or  picked  out  with  a  needle,  and 
often  an  infunilibulum  with  attached  cast  of  the  vesicles,  or  a  bronchial 
plug,  may  be  removed.  The  area  is  friable,  and  gives' way  when  the 
finger  is  thrust  into  it;  a  thick  slice  cut  from  the  surface  breaks  when 
bent;  there  is  nothing  more  characteristic  than  this  fact.  The  weight 
of  the  normal  lung  rarely  reaches  400  grams;  the  lung  in  croujious  pneu- 
monia may  weigh  three  or  six  times  as  much. 

Morbid  Histology.— On  microscopic  examination  the  blood-vessels 
are  less  distended  than  in  the  preceding  stage,  although  thev  are  still 
fuller  than  normal.  The 
i  n  rt  a  m  m  a  t  o  r  y  exud  ate 
poured  out  from  the  vessels 
now  occupies  the  vesicular 
cavity.  When  the  exudate 
passed  from  the  vessel  it 
was  liquid  (liquor  san- 
guinis), but  in  the  vesicle 
coagulation  of  the  fibrin 
has  solidified  the  intraves- 
icular  contents  and  en- 
tangled the  cellular  ele- 
ments present.  With  the 
transudation  of  the  liquor 
sanguinis  leukocytes  (bv 
diapedesis)  and  erythro- 
cytes (by  rhexis)  escape 
into  the  vesicular  cavity. 
Thus  there  are  found  in 
the  vesicle  leukocytes,  red 
corpuscles,  and  a  few  des- 
quamated epithelial  cells 
entangled  in  a  meshwork 
of  fibrin  fibrillae.  In  some 
cases  the  fibrin  is  more 
abundant  at  the  peripherv 
of  the  vesicles;  commonlv, 
\\'ithin  the  affected  alveoli. 


I-'io.  206. — Three  Ai.veou  Fillep  viitu  Fibrinous  Exudate. 
Croupous  Pneumonia,  Stage  of  Hepatization.— (5eyim<j««.) 
250  diameters. 

rt.  a,  a,  a,  a,  a,  a,  a,  a.  Alveolar  si-pta  with  sotncwhat  distended  capil- 
laries, as  at  h,  b.  c.  Meshwork  of  lihrin  orrupyinK  the  cavity  of 
the  air-vesicle.  Two  other  .lir-vesicles,  also  filled,  arc  shown.  In 
this  solidified  exudate  are  entangled  desriuamated  epithelial  cells, 
c,  from  the  alveolar  wall  and  leukocytes,  d,  d. 


however,  it  is  fairly  uniformly  distributed 
I  have  seen  the  lines  of  fibrin  parallel,  but 
usually  an  interlaced  or  web-like  fibrin  mesh  is  present.  Often  threads  of 
fibrin  pass  through  the  vesicular  wall.  The  smaller  and  sometimes  rela- 
tively large  bronchi  contain  fibrinous  plugs.  The  character  and  number  of 
the  leukocytes  are  not  always  the  same  in  different  cases,  nor  are  the  same 
cells  present  in  all  the  alveoli  of  the  affected  area.  Undoubtedly  the  viru- 
lence of  the  infecting  organism  exerts  different  chemiotactic  powers  upon 
the  individual  leukocytes  of  the  blood ;  in  some  cases  the  mononuclears 
are  the  first  to  appear  and  are  the  most  conspicuous  cells;  this  is  in 
accord  with  Pratt's  observation.  Polymorphonuclear  leukocytes  often 
appear  early  and  persist  with  decreasing  numbers  into  the  later  stages. 
The  small  amount  of  epithelium  contrasts  strongly  with  the  abundance 


6o2 


SPECIAL   PATHOLOGY 


of  that  element  in  the  air-vesicles  in  bronchopneumonia.  The  demon- 
stration of  the  presence  of  fibrin  is  best  accomplished  by  Weigert's 
method.     (See  p.   252.) 

The  solid  exudate  extends  into  the  bronchiole,  and  may,  in  rare 
instances,  reach  bronchi  of  considerable  size.  The  connective  tissue 
of  the  lung  is  the  seat  of  more  or  less  swelling,  rarely  marked,  and  the 
lymph-spaces,  particularly  near  the  hilum  of  the  organ,  are  often  dis- 
tended  by   leukocytes.     The   accumulation   of   leukocytes   around   the 


^  **',««» 


a 

Fig.  297. — Croupous  Pneumonia.  Single  Air-vesicle  in  the  Second  Stage,  with  Slightly  Contractei> 
Exudate,  (i-inch  objective,  i-inch  ocular.)  Much  higher  magnification  than  in  iiguie  296,  with  the  object 
of  bringing  out  the  fibrinous  network. 

Specimen  fixed  in  corrosive  subhmate,  infiltrated  with  paraffin,  stained  with  hematoxylin  and  eosin,  and  mounted 
in  balsam,  a,  a,  a,  a,  a,  a.  Vesicular  walls,  b.  E.xudate  in  the  air- vesicles;  during  life  the  unoccupied  area 
around  the  exudate  either  contained  serum  or  the  contraction  may  have  occurred  during  fixation  and  [hard- 
ening. 


bronchi  is  less  evident  than  in  catarrhal  pneumonia.  Suitably  pre- 
pared sections  usually  show  abundant  pneumococci,  and  the  occasional 
presence  of  other  organisms,  to  which  reference  has  been  made. 

If  evidence  of  pleurisy  did  not  develop  in  the  earlier  stages,  it  is 
certain  to  do  so  now.  A  thin  plastic  layer  or  a  marked  fibrinous  exu- 
date may  be  present.  When  a  past  pleurisy  has  obliterated  the  sac 
by  universal  adhesion,  an  exudate  is  often  present  in  the  newly  formed 
connective  tissue;     when  the  synechia  is  old  and  cicatrization  firm,  it 


OkCANS  l)K   KESPIKATION.  603 

is  less  susceptible  to  intlamniatcjry  infiltration.  Serous  exudates  are 
rare,  and,  from  the  very  nature  of  the   lung  lesion,  can  not  be  large. 

Whether  or  not  a  desquamative  process  preceded  the  stage  of  ex- 
udation at  present  under  consideration  there  is  now  induced  desqua- 
mation of  the  epithelial  lining  of  the  vesicles.  The  fibrin  contracts, 
and  free  fluitl  collects  in  the  vesicle  or  is  taken  up  by  the  lymphatics. 
The  red  blood-cells  undergo  fragmentation  and  disintegrate,  and 
bronchial  inflammation  with  some  of  the  features  of  a  bronchopneu- 
monia occurs.  The  presence  of  desquamated  and  fatty  ejjithelium  is 
associated  with  licjuefaction  of  the  coagulum  in  the  vesicle  and  con- 
version of  the  mass  into  an  emulsion  favorable  for  absorption  or  ex- 
pectoration. These  changes  usually  alter  the  color  of  the  organ  from 
red  to  gray,  and  the  condition  is  spoken  of  as  gray  hepatization.  The 
duration  of  the  stage  of  red  hepatization  no  doubt  varies;  in  three 
days  after  the  onset  of  symptoms  the  lung  may  be  gray;  on  the  other 
hand,  the  author  has  examined  a  lung  thirty-nine  days  after  the  initial 
chill,  and  thirty-seven  days  after  the  clinical  diagnosis  of  solidification, 
and  found  the  organ  still  red. 

Gray  Hepatization. — When  this  stage  is  reached,  the  lung  no  longer 
resembles,  in  its  gross  appearance,  the  previous  stage,  just  described. 
As  indicated,  the  organ  is  reddish-gray,  gray,  or  yellowish-gray,  de- 
pending upon  the  degree  to  which  the  stage  is  developed;  the  affected 
tissue  is  much  softer  and  less  tense  than  in  the  red  stage,  tearing  with 
the  greatest  ease,  but  is  less  readily  broken  by  bending.  The  incised 
surface  is  moist  and  smooth,  in  contrast  to  the  dry  and  rough  surface 
observed  in  the  red  stage.  (See  Plate  VIII.)  In  gray  hepatization 
squeezing  the  organ  leads  to  a  rather  free  flow  of  the  partly  emulsified 
inflammatory  exudate. 

The  peribronchial  lymph  nodes  are  enlarged,  the  pleurisy  is  more  ad- 
vanced, and  occasionally  the  lymphatic  channels,  running  from  the  pleura 
toward  the  mediastinum,  are  swollen  and  show  as  light  yellow  or  yellow- 
ish-red streaks.  The  involved  area  is  still  airless,  at  least  in  the  earlier 
stages  of  the  gray  change,  as  may  be  shown  by  the  tests  already  given 
when  considering  the  airless  condition  of  the  organ  in  red  hepatization. 
Under  the  microscope,  in  the  later  stage  of  gray  hepatization,  no  fibrin 
can  be  demonstrated,  but  the  vesicles  are  filled  with  cellular  elements 
resembling  those  of  bronchopneumonia;  there  are  more  leukocytes 
and  desquamated  epithelial  cells  in  varying  stages  of  granular  and  fatty 
change,  and  there  is  less  serum  than  in  the  bronchopneumonic  exu- 
date. The  coagulability  of  the  fluids  that  bathe  the  cut  surface  in 
the  gray  hepatization  can  be  shown  by  thrusting  the  organ  into  strong 
alcohol,  aqueous  solutions  of  picric  or  chromic  acid,  or  boiling  water, 
thereby  coagulating  the  albuminous  constituents  of  the  vesicular  con- 
tents. The  firmness  and  resisting  density  of  the  red  stage  can  not,  how- 
ever, be  redeveloped,  as  the  material  which  solidifies  at  this  stage  is 
albumin  undergoing  coagulation,  and  not  fibrin. 

1  erminations} — It  is  reasonable  to  suppose  that  the  gray  stage  is 
the  beginning  process  of  resolution.  As  a  result  of  autolytic  and  fatty 
changes,  the  softened  vesicular  e.xudate  eventually  becomes  transformed 
into  an  emulsion  that  is  absorbable  and  sutTiciently  liquid  to  permit 

'  For  the  formation  of  abscess  in  lobar  pneumonia  see  p.  594.  Ganprene 
resulting  from  lobar  pneumonia  is  also  there  describefl. 


6o4 


SPECIAL  PATHOLOGY. 


extrusion  from  the  air-vesicles  and  expectoration.  The  quantity  leav- 
ing the  lung  by  absorption  may  be  in  excess  of  that  escaping  by  the 
bronchi,  or  the  reverse.  The  amount  of  the  exudate  (estimated  by 
weighing  the  normal  lung  and  deducting  its  weight  from  that  of  the 
inflamed  organ)  varies  for  the  entire  lung  between  i  kilogram  and  1800 
grams;  by  observing  how  little  may  be  expectorated,  the  capacity  of 
the  absorbents  can  be,  in  part,  appreciated.  It  is  probable  that  this 
absorbed  material  is  largely  cared  for  by  the  lymphatics,  as  such  exu- 
dates are  not  likely  to  pass  through  even  capillary  walls.  The  termi- 
nation of  lobar  pneumonia  in  interstitial  pneumonia  will  be  considered 
with  the  latter.  Occasionally,  croupous  pneumonia  apparently  termi- 
nates in  tuberculosis.     In  such  cases  the  tubercle  bacillus  mav  have 


Fig.  298. — Lung,  Croupous  Pneumonia,  Organization  of  the  Intra  vesicular  Exudate. 
The  duration  of  the  pneumonia  in  the  case  from  which  this  specimen  was  obtained  could  not  be  determined  with 
accuracy.  The  clinical  data  indicated  that  the  organ  had  certainly  been  solid  over  six  weeks.  A.  Vessel 
in  intervesicular  septum.  B.  Slightly  granular  partly  organized  intravesicular  plug.  C.  Point  of  attach- 
ment of  organizing  exudate  to  inner  wall  of  air-vesicle.  D.  Prohferating  vesicular  epithelium.  In  the  ves- 
icle below  that  into  which  the  leader  from  D  runs  are  many  large  cells  apparently  epitheUal  in  origin,  lying 
free  in  the  cavity  with  a  small  amount  of  granular  detritus. 


been  in  the  lung  in  some  quiescent  nodule,  or  the  lesion  may  be  the 
result  of  a  secondary  infection  in  the  tissues  weakened  by  the  pneu- 
monic process. 

Unresolved,  organized,  or  organizing  pneumonia  results  when  re- 
solution is  long  delayed  and  active  infection  suppressed.  The  condition 
is  also  called  chronic  pneumonia.^  The  essential  phenomenon  of  the 
process  is  the  gradual  substitution  of  the  fibrinous  contents  of  the 
air-vesicles  by  fibrous  tissue  developed  from  the  intervesicular  struc- 
tures.    In  the  earlier  stages  continued  proliferation  and  desquamation 

*  See  "Nothnagel's  Encyclopedia  of  Medicine,"  American  edition,  volume  on 
"Diseases  of  the  Bronchi,  Pleura,  and  Lungs,"  1903,  p.  6S5. 


Pl.ATH    \'I1I. 


Lung.  Croupous  Pnt-umonia.  Stage  of  gray  hepatization. 
The  pleura  on  the  right  and  at  the  base  shows  the  fibrinous 
eNudate,  modified  from   Bollinger. 


ORGANS  OF   KKSI'IUATIOX.  ()0^ 

of  the  epitlK'luim  can  sometimes  be  recognized.  Outgrowths  from  the 
connective  tissue  of  the  intervesicuhir  wall  gratlually  extend  into  the 
cavities  of  the  air-cells,  which  are  eventually  tilled  by  a  hyaline,  rather 
imperfectly  developed  librous  tissue.  The  vessels  supplying  the  new 
structure  are  derived  from  the  pre-existing  capillaries  of  the  alveolar 
wall.  Before  the  completion  of  the  process  the  newly  formed  tissue 
is  attached  by  a  pedicle  to  the  wall  of  the  air-vesicle  at  the  point  from 
which  it  arose.  Eventually  the  pulmonary  tissue  contracts  and  the 
affected  structures  become  paler  and  firmer.  Any  residual  epithelial 
cells  disappear,  the  newly  formed  intra-alveolar  fibrous  tissue  merges 
\vith  the  vesicular  wall,  and  obliteration  of  the  pulmonary  parenchyma 
IS  completed. 

Lesions  That  May  Accompany  Croupous  Pneumonia. — Pleurisy  is 
always  present  in  a  pneumonia  that  reaches  the  surface  of  the  lung. 
Pleurisy  of  the  base  with  pneumonia  of  the  apex,  and  inflammation  of 
the  opposite  pleura,  are  combinations  of  pathologic  interest.  While 
the  pleurisy  is  usually  manifested  by  a  slight  plastic  or  an  abundant 
solid  exudate  and  little  serum,  it  is  not  invariably  so;  abundant  serous 
exudates  occasionally  occur,  and  empyema  (suppurative  pleurisy)  is 
not  so  infrequent  as  was  once  believed.  It  is  now  established  that 
the  pneumococcus  is  the  essential  etiologic  factor  in  various  forms  of 
pleurisy,  and  that  it  may,  without  mixed  infection,  induce  suppuration. 
Pericardial  inflammation  accompanying  pneumonia  partakes  of  the 
same  general  character  already  described  as  present  in  pleurisy,  and 
is  due  to  the  same  cause.  It  occurs  most  commonly  in  pneumonia 
of  the  left  lung,  and  especially  when  that  part  of  the  lung  overlying 
the  pericardium  is  the  seat  of  the  disease. 

The  blood  chatii^cs  that  occur  in  croupous  pneumonia,  although  not 
characteristic,  are  important.  There  is  a  notable  increase  in  the  num- 
ber of  polymorphonuclear  leukocytes;  poikilocytosis  is  occasionally 
present;  the  alkalinity  of  the  blood  is  decreased.  Although  not  of 
unvarying  import,  increase  in  the  leukocytes  is  considered  a  favorable 
prognostic  omen.  Tchistovitch  believes  he  has  demonstrated  that 
the  crisis  results  from  the  accumulation  of  phagocytes  in  the  pulmon- 
arv  tissue.  It  is  well  known  that  leukopenia  is  often  marked  in  fatal 
cases.  During  the  active  stages  of  the  disease  the  pneumococcus  is 
frequentlv  present  in  the  blood;  Rosenow  found  it  in  ninety-one  per 
cent,  of  175  cases  studied. 

The  heart  muscle  may  show  cloudy  swelling:  less  commonly,  ad- 
vanced granular  change;  and,  rarely,  a  well-marked  fatty  degenera- 
tion, or  a  frank  acute  nonsuppurative  myocarditis  may  be  in  progress. 
Mvocardial  infective  processes  have  not  been  observed.  Cardiac  thrombi 
on  the  left  side  develop  rarely,  except  immediately  preceding  death, 
and  when  associated  with  endocardial  inflammation.  Just  preceding 
death,  in  the  agonal  period,  the  slowed  and  greatly  obstructed  circu- 
lation of  the  right  side  may  be  embarrassed  by  clots  extending  from 
the  right  ventricle  into  the  smaller  ramifications  of  the  pulmonar\' 
arterv,  and,  at  the  postmortem,  these  may  l)c  pulled  out  as  long  tree- 
like or  whip-like  masses. 

Endocarditis,  both  acute  simple  and  acute  malignant,  occurs.  The 
acute  simple  form  has  been  found  without  the  observer  being  able  to 
demonstrate  pneumococci  in   the  blood  or  cardiac  lesion;     they  are. 


6o6  SPECIAL   PATHOLOGY. 

however,  commonlv  present.  In  the  maUgnant  form  of  endocarditis 
accompanying  pneumonia  the  pneumococcus  is  invariably  present,  and 
in  a  smair percentage  of  the  cases  other  organisms  of  suppuration  occur 
in  the  vegetations  and  blood. 

Monarticular  joint  injianiinations  have  been  frequently  noted,  and 
are  extremely  likelv  to  terminate  in  suppuration.  It  is  interesting  to 
note  that  pneumococci  have  been  found  in  the  affected  joints,' in  the 
pus  from  the  joints,  and  that  arthritis  has  been  induced  by  the  intra- 
articular injection  of  the  organism. 

The  extreme  selection  of  serous  surfaces  by  this  organism  and  its 
products  is  further  illustrated  in  the  occasional  peritonitis  and  inflam- 
mation of  tendon  sheaths  that  have  been  observed. 

Meningitis  is  another  illustration  of  the  liability  of  serous  surfaces 
to  suffer;  while  it  may  occur  with  malignant  endocarditis  and  be  ac- 
companied bv  embolic  processes,  both  may  be  absent.  All  the  intra- 
cranial serous  structures  may  be  the  seat  of  the  disease,  or  it  may  be 
restricted  to  a  single  fossa  or  region  or  to  the  base.  Infection  occurs 
through  the  blood  or  from  the  nasal  or  aural  spaces,  and  the  seat  of 
the  lesion  may  indicate  the  source  of  the  infection.  The  process  may 
be  restricted  to  the  meninges  or  the  brain  structure  may  be  involved. 
Involvement  of  the  spinal  meninges  has  been  observed. 

A  number  of  mucous  membranes  may  be  infected  by  the  pneu- 
mococcus, either  during  pneumonia  or  independently;  the  most  fre- 
quent are  the  ear  {otitis  media)  and  mucous  surfaces  of  the  nasal  ap- 
pendages; e.  g.,  abscess  of  the  frontal  sinus,  containing  the  diplococcus 
and  followed  "by  a  diplococcus-menmgitis.  Anders  reports  three  cases 
of  cholecvstitis^  complicating  croupous  pneumonia.  Suppurative  par- 
otitis (the  pus  containing  the  diplococci)  is  occasionally  observed. 
Fibrinous  inflammations  of  the  stomach,  colon,  and  other  mucous  sur- 
faces may  occur;  hemorrhagic  and  gangrenous  processes  are  less  fre- 
quent, except  in  the  embolic  phenomena  which  accompany  malignant 
endocarditis.  The  epithelium  of  the  mucosae,  liver,  and  kidneys  is 
usually  cloudv.  The  renal  lesion  in  croupous  pneumonia,  manifested 
by  the  presence  of  more  or  less  albumin  in  the  urine,  rarely  passes  on 
to  an  inflammatorv  condition  which  persists  after  the  disappearance  of 
the  initial  cause.  "  In  fatal  cases  an  acute  diffuse  or  acute  nonsuppura- 
tive interstitial  nephritis  is  often  observed.  Thrombosis  of  one  or  more 
veins  and  thromhoarteritis  sometimes  occur.  Either  of  these  may  give 
rise  to  gangrene.  An  instance  of  acute  thyroiditis,  the  pus  of  wdiich 
contains  pneumococci,  is  recorded.  Among  the  complications  involv- 
ing the  nervous  system  may  be  mentioned  acute  cerehritis,  monoplegias, 
hemiplegias,  and  neuritis. 

Bronchopneumonia^ — This  disease  is  also  known  as  lobular  pneu- 
monia, a  name  objectionable  in  that  it  does  not  indicate  the  bronchial 

1  Steven,  "Lancet,"  Sept.  20,  1902,  p.  791.  Richat  and  Goepfert,  "Rev. 
mens  des  Mai.  de  I'Enfance,"  Aug..  1902.  Joachmann  and  Moltrecht,  "Zen- 
tralbl.  f.  Bakt.,"  1903,  xxxiv,  15.  Robertson,  "Scottish  Med.  and  Surg.  Jour.. 
June.  1903,  p.  485.  Conner,  "N.  Y.  Med.  Jour.,"  Dec.  26,  1903,  p.  1213.  Laig- 
nel-Lavastine  and  Voisin,  "Arch.  Gen.  de  Med.  et  path.  Anat.,"  March,  1904, 
p  206.  Bovaird,  "Med.  News,"  April  30,  1904,  p.  820.  Hardy,  "Lancet. 
Sept.  24,  1904,  p.  885.  Woolstein,  "Jour,  of  Exper.  Med.,"  1905,  vol.  vi,  P-  39i- 
Sutherland,  "  Harveran  Soc.  of  London,"  Feb.  9,  1904;  also  "Lancet,  Feb. 
25,   1905,  p.  502. 


ORGAN'S   OF    kKSPIKATHiN.  607 

association  that  is  always  ])rcsent,  and  also  in  the  fact  that  embolic 
processes  may  be  essentially  lobular  and  still  bear  no  relation  in  point 
of  cause  or  patholofjy  to  the  condition  under  consideration.  The  name 
catarrhal  pneumonia  indicates  the  character  of  the  exudate,  but  not 
all  Its  component  ])arts  are  catarrhal  in  point  of  orij^in.  and  the 
chanj^es  to  be  noted  in  the  vesicular  wall  make  the  process  more  than 
a  superficial  inflammation.  The  dcsi^mation  capillary  bronchitis  is  ob- 
jectional)le,  as  it  does  not  indicate  the  acconi])anyin.!.(  vt-siiular  change. 
The  term  dissiiiiifiiitcd  p)u-nmouia  indicates  the  wide  distribution  of 
the  ])rocess  in  contradistinction  to  the  more  or  less  circumscribed  lesion 
of  croupous  pneumonia.  The  tenn  catarrhal  brotichopiicnuioiiia  seems 
no  better  than  bronchopneumonia  alone.  The  various  other  synonyms 
that  have  been  given  in  attempts  to  indicate  the  location  or  character 
of  the  lesion,  the  cause  or  termination,  are  either  obsolete  or  objection- 
able. 

Causes. — Bronchopneumonia  is  not,  as  a  rule,  a  primary  disease, 
but  arises  secondarily  in  some  other  process.  Conner  has  collated  the 
experiences  of  a  large  number  of  observers  and  concludes  that  probably 
less  than  thirty  per  cent,  to  thirty-five  per  cent,  of  the  cases  are  prim- 
ary. In  nearly  all,  if  not  all,  the  cases  of  this  disease  the  bronchiole 
or  the  passage  above  is  the  initial  seat  of  the  lesion,  and  the  vesicle 
is  secondarily  affected.  When  the  inflammatory  process  follows  dis- 
ease of  the  intervesicular  wall,  such  as  tuberculosis  of  that  structure, 
one  can  conceive  the  initial  lesion  to  have  been  in  the  vesicle;  but, 
aside  from  this  factor, — contiguous  disease, — bronchopneumonia,  as  the 
name  indicates,  begins  essentially  as  a  bronchial  inflammation. 

While  no  specific  germ  has  been  adduced,  the  phenomena  are  those 
commonly  attributed  to  infection  or  infectious  products.  The  pneumo- 
coccus  of  Frankel  is  present  in  a  relatively  large  percentage  of  the 
cases;  it  may  occur  alone  or  be  associated  with  other  organisms.  Meu- 
nier  has  shown  that  the  only  organism  present  may  be  the  Bacillus 
influenzae;  streptococci  and  other  pyococci  are  sometimes  found.  The 
condition  is  so  constantly  a  part  of  various  infections  that  it  wi  uld 
seem  that  the  definite  anatomic  alterations  to  be  described  might  arise 
from  a  multitude  of  causes,  a  few  acting  singly,  or  the  combination  of 
two  or  more  factors.  The  fact  that  bronchopneumonia  occurs  most 
constantly,  as  an  important  process,  in  the  young  and  the  aged  seems 
to  indicate  some  peculiarity  of  tissue  at  those  periods;  this  has  been 
assumed  to  be.  in  part  at  least,  an  inability  of  the  terminal  air-passages 
to  evacuate  themselves,  owing  to  the  faulty  or  poorly  developed  elastic 
tissue  in  the  lung  of  the  young,  or  muscular  weakness  of  the  respiratory 
apparatus  in  the  two  extremes  of  life;  further,  the  epithelium  of  the 
infant,  in  the  transitional  stages  of  development,  is  most  abundantly 
exfoliated  as  a  result  of  an  irritation  that  adult  tissues  would  resist. 
That  such  excessive  susceptibility  of  the  mucous  surfaces  exists  is 
shown  in  the  gastro-intestinal  diseases  of  childhood  equally  as  much 
as  in  the  pulmonary  lesions.  Bovaird  states  that  in  the  Foundling 
Hospital  forty  per  cent,  of  the  dead  have  bronchopneumonia.  A  similar 
susceptibility  is  manifest  in  old  age. 

Unsanitan,'  surroundings,  crowding,  poorly  ventilated  sleeping  or 
living  rooms,  are  all  predisposing  elements.  Exposure,  cold,  dampness, 
and  other  incidents  of  the  winter  months  show  a  marked    influence. 


6o8  SPECIAL  PATHOLOGY. 

the  disease  being  most  prevalent  from  November  to  May,  inclusive, 
reaching  its  acme  in  the  uncertain,  varying,  climatic  conditions  of  the 
early  spring  months.  Its  relation  to  the  infections  is  shown  in  the 
constancy  with  which  it  develops  in  the  presence  of  those  conditions; 
of  the  acute  infectious  diseases,  measles  is  the  one  with  which  it  is 
most  frequently  associated,  although  diphtheria,  both  pharyngeal  and 
laryngeal,  especially  the  latter,  is  commonly  the  immediate  precursor 
or  accompanying  lesion.  Scarlet  fever  and  whooping-cough  are  usu- 
ally, and  typhoid  fever  and  smallpox  may  be,  accompanied  by  broncho- 
pneumonia. 

When  the  respiratory  apparatus  is  the  seat  of  any  of  the  specific 
infectious  diseases,  whether  acute  or  chronic, — anthrax  (as  in  wool- 
sorter's  disease),  tuberculosis,  glanders,  leprosy,  etc., — bronchopneu- 
monia is  extremely  liable  to  occur;  and  when  one  of  these  processes 
involves  the  lung,  catarrhal  pneumonia  is  inevitable.  The  bacillus  of 
tuberculosis  in  the  lung,  whether  in  the  cavities  of  the  alveoli,  as  when 
aspirated  from  above,  or  in  the  vesicular  or  bronchiole  wall,  as  when 
brought  by  the  blood  or  lymphatics,  always  incites  a  bronchopneu- 
monia, which  is  modified  by  the  tuberculous  process,  but  is,  neverthe- 
less, a  characteristic  lesion.  Bronchopneumonia  may  be  present  in 
syphilis  of  the  lung. 

When  infectious  materials  are  drawn  into  the  lung,  as  in  the  de- 
glutition and  aspiration  pneumonias,  to  which  reference  has  already 
been  made,  bronchopneumonia  and  other  accompanying  infective  pro- 
cesses ensue;  that  bronchopneumonia  is  not  the  whole  of  the  process 
is  shown  by  the  frequency  with  which  suppuration  or  gangrene  may 
follow.  (See  Pulmonary  Suppuration,  p.  592.)  Bronchopneumonia 
also  terminates  fibrinous  or  lobar  pneumonia  when  resolution  is  gradu- 
ally reestablishing  the  normal. 

In  conclusion,  it  remains  to  be  said  that  any  condition  that  lowers 
the  vitality  of  the  individual,  that  weakens  the  avenues  open  for  in- 
fection, that  depresses  or  debilitates,  favors  the  development  of  broncho- 
pneumonia. To  this  group  of  causes  belong  Bright's  disease,  chronic 
heart  disease,  convalescence  from  acute  processes,  or  the  debilitating 
influences  of  more  chronic  ones.  Bronchopneumonia  to  a  varying  de- 
gree always  accompanies  pneumoconiosis. 

Morbid  Anatomy. — In  recent  cases,  acute  in  time,  the  lung  is  more 
voluminous  than  normal,  and  does  not  collapse  with  usual  promptness, 
and  may  not  shrink  in  the  least  when  the  chest  is  opened;  there  is  not 
that  dense  firmness  of  the  tissue  involved  so  constantly  present  in  fibrin- 
ous or  lobar  pneumonia,  and  on  superficial  examination  the  lung  ap- 
pears to  crepitate  throughout;  examined  more  closely,  areas  that  do 
not  crepitate  are  easily  found;  while  firm,  they  are  not  dense,  and 
are  small  nodules  in  contrast  to  the  large  areas  of  fibrinous  pneumonia. 
On  the  surface  of  the  lung,  as  a  rule,  near  the  base  are  areas  sunken 
below  the  surface,  blue  or  bluish-brown  in  color,  usually  isolated  and 
small,  although  in  rare  instances  almost,  if  not  quite,  all  of  a  lobe  may 
be  involved  in  the  atelectatic  process.  Usually,  such  areas  can  be 
reexpanded  by  forcing  air  into  the  bronchus.  The  area  joining  that 
of  collapse  is  not  uncommonly  emphysematous,  as  are  the  anterior 
and  apical  margins.  At  scattered  points  will  be  found  projecting  areas, 
over  which  the  pleura  may  be  rough  or  even  show  a  beginning  exudate ; 


ORGAN'S  OF   RESPIkATION'. 


609 


the  larger  the  consoUdated  portion,  the  more  evident  the  pleurisy. 
On  section,  the  surface  is  usually  dark  or  reddish,  although  in  adults 
it  mav  be  gray  at  points — not  unlike  the  gray  stage  of  fibrinous  pneu- 
monia. The  surface  is  smooth  and  moist,  and  drips  blood  or  bloody 
senmi.  The  outline  of  the  affected  lobules  can  be  seen,  or,  where  a 
nimiber  have  run  together,  they  usually  manifest  different  stages  of 
the  process,  and  -can  in  that  way  be  distinguished.  A  suitable  lobule, 
on  longitudinal  section,  shows  the  grape-like  structure  of  the  lung, 
with  alveoli,  infundibula,  and  bronchiole  filled  with  puriform  mucus; 
a  transverse  section  reveals  the  central  bronchiole,  containing  a  ten- 
acious plug  of  mucus,  surrounded  by  distended  vesicles  and  the  ad- 
jacent collapsed  lobules.     Adjoining  the  inflamed  tissue  the  areas  of 


Fig.  399. — Lfsx,  I.nxluding  a  Small  Bronchus.  Brontwtis  and  BRONc-HOPNtuMosiA. 
The  bmnchus  (center  of  field)  shows  desquamation  of  epithelium,  m.iny  of  the  cells  lioing  completely  detache*! 
and  others  in  process  of  detachment.  The  bronchial  wall  is  infiltrated  by  mononuclear  leukocytes.  Many 
of  the  adjacent  air-vi-siclos  contain  a  granular  deposit  resulting  from  precipitation,  during  fixation,  of  an 
albuminous  exudate;  in  this  granular  material  arc  var>'ing  numlnrs  of  mononuclear  cills  and  epithelial  cells, 
the  latter  having  been  cast  off  the  alveolar  walU. 

collapse  may  be  readily  distinguished,  or  they  may  be  indistinct;  if  de- 
fined, they  are  dark,  smooth,  airless,  and  instead  of  bulging  when  cut, 
apparently  retract;  when  immediately  subpleural,  there  may  be  ecchy- 
mosis  in  or  over  them;  when  not  well  defined,  the  outline  is  formed 
by  darkish  bands  traversing  the  lobes  in  an  irregular  manner.  The 
peribronchial  lymphatic  nodes  are  usually  swollen  and  edematous,  owing 
to  the  effort  made  to  care  for  the  degenerative  product  of  the  bronchial 
and  vesicular  inflammation.  In  some  cases  the  lymphatics  traversing 
the  lung  are  also  distended. 

Morbid  Histology. — If  a  drop  of  the  fluid  that  fills  the  air-sj)aces 
be  squeezed  out  upon  a  slide,  it  will  be  found  composed  of  germinal, 
granular,    and    fatty    epithelium,    a    varying    number    of    leukocytes, 
40 


6io 


SPECIAL  PATHOLOGY. 


rarely  any  red  blood-cells.  The  fluid  exudate  must  be  solidified  before 
making  sections  for  histologic  examination;  this  may  be  accomplished 
by  thrusting  a  part  of  the  affected  tissue  into  boiling  water,  and  thus 
coagulating  the  albumin  in  the  serum  and  incarcerating  the  cellular 
elements;  such  a  process  alters  the  surrounding  structures  too  pro- 
foundly to  be  commendable,  and  the  same  object  may  be  secured  by 
using  absolute  alcohol  or  Flemming's  or  Hermann's  fixing  solutions. 
(See  p.  33.)  Infiltration  is  imperative  in  order  to  retain  the  histologic 
structure  in  place. 

Examination  of  properly  prepared  sections  discloses  the  alveoli 
filled,  not  with  a  fibrin-bearing  exudate,  as  in  lobar  pneumonia,  except 
in  a  very  few  scattered  vesicles,  but  with  a  mucoid  exudate  containing 
the  cellular  elements  previously  indicated,  the  epithelium  being  espe- 
cially conspicuous.  The  bronchiole  lumen  will  be  found  occluded  by 
the  same  exudate,  the  wall  infiltrated  by  leukocytes,  and  the  integral 
elements  pushed  apart,  typifying  the  swelling  that  was  present.  Longi- 
tudinal sections  reveal,  in  the  bronchiole,  more  or  less  irregularity  in 

the  transverse  diameter — saccular  di- 
a  a  latation.     The  infundibulum  and  its 

surrounding  vesicles  are  filled  with 
a  similar  exudate,  and  the  same 
cellular  infiltration  of  the  vesicular 
walls  may  be  found.  Toward  the 
margin  of  the  affected  lobule  the 
distention  is  less  marked,  and  the 
alveolar  epithelium  shows  desqua- 
mation and  marked  fatty  changes. 
The  capillaries  of  the  walls,  both 
vesicular  and  bronchial,  are  usually 
distended  and  surrounded  by  leuko- 
C}^es.  The  lymphatic  channels  lead- 
ing from  the  affected  areas  are 
usually  engorged.  In  the  peribron- 
chial lymphatics  more  or  less  swelling 
and  infiltration  are  manifest. 
In  the  bronchopneumonia  accompanying  the  aspiration  of  foreign 
bodies  into  the  bronchi  the  bacteria  present  infiltrate  the  connective 
tissue,  abundant  leukocytic  infiltration  occurs,  and,  if  the  processes 
have  sufficient  time,  suppuration  or  gangrene  usually  ensues. 

Terminations. — Acute  bronchopneumonia  undergoes  resolution  rap- 
idly once  the  process  begins;  upon  withdrawal  of  the  cause  the 
lymphatics  and  blood-vessels  dispose  of  the  unexpectorated  exudate, 
epithelium  rehabilitates  the  denuded  walls,  and  resorption  of  cellular 
products  in  the  ve^'cular  and  bronchiole  tissues  follows  the  removal 
of  the  Hquid  exudates  that  caused  the  swelHng  to  which  reference  was 
made  while  considering  the  histology.  The  feebleness  of  the  respira- 
tion and  the  reduced  resistance  may  enable  deposited  bacteria  to  secure 
a  more  or  less  permanent  abode.  That  pyogenic  and  saprophytic  bac- 
teria may  induce  suppuration  and  gangrene  has  already  been  stated. 
In  the  distended  vesicles  or  lobules  tubercle  bacilli  may  lodge,  and 
the  characteristic  phenomena  of  tuberculosis  ensue,  constituting  a  tuber- 
culous infection  secondary  to  the  bronchopneumonia.     This,  while  pos- 


FiG.  300. — Two  Alveoli  and  a  Part  of  a  Third 
FROM  Lung  in  Catarrhal  Pneumonia. 

a,  a,  a.  Walls  of  the  alveoli,  b.  Desquamated  epi- 
thelial cells  from  the  walls  of  the  alveolus,  c. 
Alveolus  filled  %vith  catarrhal  exudate,  d. 
Leukocyte. 


OKGAXS   t)F   KESPIKATIOX.  6ll 

sible,  is  no  doubt  rare,  and  where  caseation  with  fibroid  encapsulation 
of  the  caseous  area  is  found  postmortem,  it  is  probable  that  the  dis- 
ease was  tuberculous  from  the  start,  but  that  the  conservative  elements 
limiteil  the  ])rocess;  these  areas  may  become  calcareous,  and  exhibit 
the  other  ])henomena  so  constantly  associated  with  fiuiescent  tubercu- 
losis. It  is  ]X)ssible  for  tuberculosis  to  follow  a  more  wide-spread  in- 
filtration, or  the  tubercle  bacillus  may  have  induced  the  pneumonia. 
At  one  time  it  was  believed  that  caseation  and  fibroid  change 
were  legitimate  terminations  of  bronchopneumonia,  and  recognized 
as  frequently  occurring  conditions.  While,  as  already  stated,  one  can 
conceive  of  a  simple  nontuberculous  area  of  consolidation  becoming 
fibroid  and  limited,  independent  of  the  bacillus  of  tuberculosis,  still, 
when  caseation  and  calcareous  infiltration  are  found,  the  evidence  is 
clearly  that  of  a  "healed-in"  ttiberculous  focus. 

I'lic  coniplicaiions  of  bro}ichopuciinioiiia  are  fewer  and  occur  less  fre- 
quentlv  than  those  observed  in  croupous  pneumonia.  The  catarrhal 
lesions  of  the  upper  air-passages  are  not  properly  considered  as  compli- 
cations, limpyema  is  probably  the  most  important  coincident  affection  or 
sequel,  .l/cningi/i^  is  occasionally  observed ;  Hardy  encountered  it  eight 
times  in  150  cases;  he  places  it  among  the  causes  of  bronchopneumonia. 
Joint  coDt plications  are  infrequent,  but  Bichat  and  Goepfert  have  shown 
ithat  thev  may  occur  and  be  due  to  the  pneumococcus  or  other  pyogenic 
organisms.  Endocardial  and  myocardial  changes  of  importance  are  usu- 
ally the  result  of  the  condition  which  caused  pneumonia,  and  not  truly 
a  consequence  of  the  latter;  to  this  statement  there  are  occasional  ex- 
ceptions. In  some  cases  a  leukocytosis  occurs.  Simple  uncomplicated 
attacks  are  rarely  attended  by  changes  in  the  kidneys  or  important 
structural  alterations  in  the  liver. 

Fibroid  pneumonia,'  interstitial  pneumonia,  chronic  interstitial  pneu- 
monia, pnl))ionary  cirrhosis,  or,  more  properly,  pnlmoiiary  sclerosis, 
fibroid  induration,  fibroid  lung,  with  various  other  synonyms,  is  a  chronic 
productive  inflammatory  process,  involving  essentially  the  connective 
tissue  of  the  organ,  with  increase  of  the  fibrous  elements  and  more 
or  less  contraction  of  the  newly  formed  structures.  The  degree  to 
which  the  change  may  progress  is  dependent  upon  many  factors. 
The  fact  that  the  process,  practically  always,  is  secondary  to  some 
other  lesion,  has  led  to  a  multitude  of  names,  each  assuming  the  exist- 
ence of  a  separate  condition.  No  inflammation  of  the  lung  tissue,  no 
invasion  of  the  pulmonary  structure  by  foreign  bodies,  whether  coal 
or  iron,  bacteria  or  morbid  growths,  is  likely  to  occur  without  a  cer- 
tain amount  of  increase  in  the  fibrous  tissue.  This  statement  indi- 
cates the  character  of  the  causes  which  are  active.  Fibrinous  pneu- 
monia, bronchopneumonia,  tuljerculous  ])neumonia,  and  other  infectious 
processes  which  may  induce  inflammation, — as  syphilis,  leprosy,  and 
actinomvcosis,  pneumoconiosis,  and  inflammation  of  the  pleura, — may 
all  be  cited  as  etiologic  factors. 

When  the  cause  is  limited  to  a  part  of  the  lung,  the  fibroid  change 
may  involve  only  a  small  area;  thus,  a  small  circumscribed,  possibly 

'  See  Vogel,  "Ziegler's  Beitr.,"  iqoo.  vol.  xxviii.  Auld,  "Brit.  Med.  Jour.." 
Feb.  4,  IQ05,  p.  2^6.  Also  article  on  ■Chronic  Pneumonia,"  "  Nothnaijers  Ency- 
clopedia of  Practical  Medicine,"  American  edition,  volume  on  "Diseases  of  the 
Bronchi,  Pleura,  and  Lungs,"  1903,  p.  685. 


6l2  SPECIAL  PATHOLOGY. 

quiescent  tuberculous  process  in  an  apex  may  be  surrounded  by  an 
insignificant  area  of  advanced  interstitial  fibroid  change.  When  a  pro- 
tracted bronchopneumonia  has  involved,  for  any  great  length  of  time, 
the  entire  pulmonary  structure,  increase  of  fibrous  tissue  will  be  present 
throughout  both  lungs,  the  bronchial  walls  will  be  thickened,  and  many 
intervesicular  septa  more  or  less  fibroid.  Attempts  have  been  made 
to  classify  these  various  stages  and  degrees,  but  one  lung  may  be  in 
one  stage  and  the  other  contain  similar  lesions  developed  to  quite  a 
different  degree;  one  lung  may  be  universally  fibroid,  the  other  show 
only  points  of  fibroid  change— the  so-called  local  fibroid  pneumonia. 
As  to  source  or  cause,  the  fibrous-tissue  increase  follows  out  certain 
lines. 

In  fibrinous  pneumonia  the  area  involved  may  not  undergo  resolu- 
tion, but  pass  into  this  condition  of  fibroid  change.  The  connective- 
tissue  cells  in  the  vesicular  wall  proliferate,  and  the  fibrinous  plugs 
occupving  the  vesicles  and  infundibula  pass  through  the  various  stages 
of  embryonic  and  granulation  tissues,  and  eventually  the  mass  becomes 
converted,  more  or  less  completely,  into  fibrous  tissue — a  condition 
spoken  of  as  the  gray  induration  of  unresolved  pneumonia.  The  area 
is  gray,  firm,  elastic,  and  smooth,  and  closely  resembles  recently  de- 
veloped but  slightly  contracted  connective  tissue.  The  process  is  one 
of  the  infrequent  terminations  of  croupous  pneumonia.  In  persistent 
bronchopneumonia  the  inflammatory  changes,  already  noted  as  occur- 
ring in  the  vesicular  wall,  lead  to  thickening,  and  in  the  areas  of  col- 
lapse this  may  preclude  restoration  of  function.  The  most  marked 
development  of  fibrous  tissue  occurs  around  the  bronchi, — a  peribronch- 
itis,— followed  by  the  fibrous  invasion  extending  to  the  septa  between 
lobules,  and  eventually  to  the  vesicular  walls. 

When  fibroid  lung  follows  an  inflammation  of  the  pleura, — pleuro- 
genous  interstitial  pneumonia, — the  condition  is  usually  associated  with 
plastic  pleurisy,  the  formative  inflammatory  process  extending  into 
the  lung  along  the  course  of  the  interlobular  septa  and  peribronchial 
lymphatics.  This  differs  etiologically  from  the  fibroid  condition  already 
described  as  occurring  in  the  more  or  less  completely  collapsed  lung 
with  thickening  of  the  pleura  and  constriction  of  the  lung  by  an  inter- 
stitial process;  the  shrinking  or  contraction  of  the  organ  is  secondary 
to  the  development  of  new  fibrous  tissue;  in  the  collapsed  lung  the 
fibroid  change  is  secondary  to  the  pleural  thickening  and  the  cessation 
of  function. 

The  development  of  fibroid  lung  in  pneumoconiosis  has  already 
been  considered ;  ^  it  remains  only  to  be  said  that  the  increase  in 
fibrous  tissue  there  noted  is  due  to  the  direct  influence  of  the  foreign 
bodies  in  the  connective  tissue  of  the  lung,  exactly  as  fibrous  tissue 
develops  around  any  extraneous  body  in  the  process  of  "healing-in"; 
to  this  must  be  added  the  thickening  incident  to  the  accompanying 
inflammation  of  the  mucous  surface,  such  as  always  occurs  when  per- 
sistent inflammation  leads  to  fibrous  changes  in  the  submucosa.  (See 
Fig.  269,  p.  544.) 

Morbid  Anatomy. — From  the  foregoing  it  will  be  seen  how  varied 
the  appearance  of  such  organs  must  be.     In  the  simpler,  less  extensive, 

1  See  Pneumoconiosis,  and  other  infiltrations  of  mucous  membranes,  p.  542; 
also  Chronic  Catarrhal  Inflammation  of  Mucous  Membranes,  p.  546. 


OKllANS   OK    RKSPIkATIOX, 


6 '3 


and  ^'cnerallv  (lissenunaUMi  k'sioii  the  or.ijan  is  lirnier  than  normal,  and 
on  the  pleura  the  hbroid  areas  between  lobes  or  lobules  may  be  recog- 
nized. On  section,  these  areas  of  fibrosis  ai)])ear  as  gray,  more  or  less 
pigmented    masses, 

usually  radiating  from  •• 

the  central  bronchus 
along  the  lines  of  the 
interlobar  or  inter- 
lobular septa.  The 
uninvolved  portions 
of  the  lung  ma\'  be 
slightly  emphysema- 
tous, and  the  elasticity 
of  the  organ  so  mod- 
ified that  it  collapses 
slowly,  if  at  all.  In 
more  advanced  cases, 
or  when  the  lesion  is 
more  marked,  the 
fibrous  tissue  involves 
a  whole  lobe,  or  a 
greater  part  of  a  lobe, 
and  is  conspicuous ; 
on  section,  it  differs 
in  degree  only  from 
the  next  condition  to 
be  described,  in  which 
the  whole  of  a  lung  is 
usually  involved. 

This  constitutes 
tnie  cirrhosis,  or,  bet- 
ter, sclerosis  of  the 
lung.  Of  necessity, 
the  process  is  uni- 
lateral, and  the  cor- 
responding chest-wall 
shrunken  and  pulled 
in,  and  the  shoulder 
lower  than  that  of  the 
unaffected  side.  The 
opposite  lung  is  vol- 
uminous, extends  far 
beyond  the  median 
line,  is  emphysemat- 
ous, and  the  mediasti- 
nal tissues,  heart,  and 
great  vessels  are  dis- 
placed toward  the 
affected    side.     The 

diminished  volume  of  ■  .    • 

the  fibroid  lung  mav  be  incredible ;  the  author  saw  a  case  in  which  it 
was  not  larger  than' two  small  fists,  and  Osier  speaks  of  an  instance  in 


.  30..    »..j..^., -  —  — 

Hyaloserositis,  a.su  a  Ierminal  Catarrhal  Pneumonia  Resulting 
FROM    Concurrent    Inkection   by  the  Tubercle   Bacillus  and 

Pneumococcus. 

.1.  Greatly  thickened  plour.i.  li  Dibtcd  bronchi.  C.  One  of  many 
hro.id  sir.ita  of  tilirous  tissue  irrrKui.irlv  traversing  the  organ.  D. 
I^-irgc  ci-seous  lymph  n'xic  near  hilum  of  Iuhr.  and  immediately  adja- 
cent to  the  .lorta.  a  section  of  whidi  is  shown  just  alMivc.  The  aorta  is 
the  scat  of  slight  atheroma. 


6l4  SPECIAL  PATHOLOGY. 

which  the  affected  organ  was  not  found  (!).  The  lung  is  firm,  at  times 
doughy  and  airless,  and  resists  the  knife  to  an  unusual  degree.  In  the 
pleurogenous  form,  and  when  the  process  follows  croupous  pneumonia, 
the  pleura  may  be  adherent,  and  is  always  very  much  thickened;  when 
the  condition  results  from  intrapulmonary  causes,  the  pleura  may  not 
be  affected.  The  bronchi  are  nearly  always  more  or  less  dilated,  some- 
times to  an  enormous  degree.  (See  Bronchiectasis,  p.  579.)  The  cut 
surface  shows  the  fibroid  character  to  advantage;  the  blood-vessels 
and  bronchi  are  embedded  in  a  mass  of  grayish,  rather  dense,  often 
hyaline,  and  sometimes  partly  calcified,  fibrous  tissue.  The  slowness 
of  the  circulation  and  the  loss  of  functional  activity  in  the  affected  organ 
render  infection  readily  possible;  rareh^  this  may  be  pyogenic,  and 
leave  a  cavity.  Tuberculosis  as  a  cause  and  tuberculosis  as  a  sequence 
— an  infection  of  a  point  of  least  resistance,  as  this  truly  is — occurs 
in  no  small  number  of  cases;  the  relation  of  the  tuberculous  process 
to  the  interstitial  change  can  usually  be  inferred  by  the  location  and 
character  of  the  lesion.  The  cases  of  tuberculous  origin  frequently  show 
an  apical  cavity  and  some  evidence  of  infection  in  the  opposite  lung. 

Morbid  Histology. — This  has  been  partly  considered  in  the  preced- 
ing remarks  and  varies  as  does  the  gross  anatomy.  In  the  less  marked 
cases  fibrous  tissue  in  varying  stages  of  development  ma}'  be  found  in 
the  vesicular  walls  and  around  the  bronchi;  in  the  advanced  cases — 
those  last  considered — the  bands  of  fibrous  tissue  have  compressed  and 
obliterated  the  pulmonary  vesicles,  and  converted  the  areas  involved 
into  irregularly  outlined  masses  of  cicatricial  tissue.  A  varying  amount 
of  catarrhal  inflammation  may  be  evident  in  the  vesicular  structure  or 
the  change  indicative  of  a  past  catarrhal  process  may  remain.  Evi- 
dence of  tuberculosis  can  often  be  demonstrated  microscopically  when 
the  grosser  lesions  are  lacking. 

Termination. — Under  the  most  favorable  circumstances,  in  nontuber- 
culous  cases,  arrest  of  the  process  is  all  that  can  be  expected.  This 
is  dependent  upon  the  possible  removal  of  the  cause.  In  a  vast  major- 
ity of  cases  tuberculosis  is  the  last  and  fatal  stage;  Auld  reports  an 
instance  in  which  tuberculosis,  beginning  in  an  unresolved  pneumonia, 
became  arrested.  The  limited  fibroid  change — local  interstitial  pneu- 
monia— around  a  point  of  tuberculous  infection  may  be  beneficent  in 
that  it  is  possible  by  this  means  to  limit  the  dissemination  of  a  localized 
tuberculosis,  and  the  increase  of  connective  tissue  with  calcareous  in- 
filtration, as  so  often  occurs,  is  no  doubt  the  local  reaction  to  an  infec- 
tion by  which  contiguous  and  general  extension  is  prevented. 

Puimonary  tuberculosis/  tuberculosis  of  the  lung,  axid  tuberculous 

^Aufrecht,  "Berl.  klin.  Woch.,"  Oct.  21.  1901.  Baumgarten.  ■'Wien.  klin. 
Woch.."  1901,  No.  2.  Heymans,  "Arch,  de  Pharmacodynamie  et  Therap.," 
tome  xiii,  p.  469.  Roberts,  "Lancet,"  March  29,  1902.  Ribbert.  "Deut.  med. 
Woch.,"  April  24,  1902.  Watanabe,  "Ziegler's  Beitr.,"  1902,  Bd.  31,  p.  366. 
Esser,  "Deut.  med.  Woch.,"  March  4,  1902.  Schmorl,  "Miinch.  med.  Woch.," 
Aug.  19,  1902,  p.  1379.  Woodhead,  '"Report  of  the  Henry  Phipps  Institute  for 
the  Studv,  Prevention  and  Treatment  of  Tuberculosis,"  Philadelphia,  vol.  i,  1904. 
Orth,  "Berl.  klin.  Woch.,"  1904,  Nos.  11,  12,  and  13.  Owen,  "Brit.  Med.  Jour.," 
April  2,  1904,  p.  765.  Perkins,  "Med.  News,"  April  16,  1904,  p.  744.  Blumer 
and  Lartigau,  "California  State  Jour,  of  Medicine,"  Sept.,  1904.  Swan,  "Pro- 
ceed, of  the  Phila.  Co.  Med.  Soc,"  Feb.  29,  1904,  vol.  xxv,  n.  s.,  vol.  vi.  Weber, 
"Lancet,"  April  2,  1904,  p.  924.  Bro^Am  and  Pope,  "Amer.  Jour,  of  Med.  Sci.," 
Oct..  1904,  p.  619.     Abrikossoff,  "Virchow's  Arch.,"  1904.  Bd.  178,  p.  173.     Was- 


ORGANS  OF  RESPIRATION'. 


615 


phthisis,  arc  names  applied  to  the  pulmonary  manifestations  of  infec- 
tion bv  the  tubercle  bacillus.  The  entrance  of  the  tubercle  bacillus 
mto  the  jjulmonary  parenchyma  may  be  manifested  in  a  number  of 
wavs,  dependinj^  upon  the  resistance  of  the  individurd,  the  virulence 
of  the  infecting  organism,  and  the  route  of  the  infection,  as  well  as 
upon  the  extent  of  bacterial  distribution  in  the  ])ulmonary  tissue.  It 
is,  of  course,  in  all  its  forms  due  to  the  tubercle  bacillus.'  The  organ- 
ism may  reach  the  lung  through  at  least  three  important  avenues: 
(i)  bronchi,  (2)  lymphatics,  (3)  blood-vessels,  and  possibly  by  direct 
invasion  from  adjacent  tissues. 

Aerogoioiis  or  piicuinatogoiotis  injection  occurs  through  the  inhala- 
tion of  tubercle  bacilli.  It  is  probable  that  when  the  bacilli  are  de- 
posited within  the  larger  bronchioles,  invasion  of  the  peribronchial 
tissue  is  less  likely  to  occur;  and  that  when  the  tubercle  germs  escape 
extrusion  by  the  activity  of  the  ciliated  epithelium  and  by  expectora- 
tion, they  may  pass  through  denuded  areas  in  the  bronchial  wall,  reach- 
ing the  peribronchial  tissue,  and  eventually  a  lymphatic  node,  in  which 
they  give  rise  to  tuberculosis.  In 
other  instances  a  primary  tubercu- 
lous lesion  is  produced  in  the  larynx, 
trachea,  or  larger  bronchi,  and,  from 
these  structures,  invasion  of  the 
lymph-nodes  or  pulmonary  paren- 
chyma may  occur. 

From  a  primary  tuberculous  focus 
in  the  larynx,  trachea,  or  larger  bron- 
chi, or  from  a  tuberculous  area  in  the 
lung,  infected  material  may  be  aspir- 
ated into  the  smaller  bronchi,  or  even 
into  the  vesicular  structure.  It  is 
probably  more  common  for  the  organ- 
ism to  reach  the  finer  ramifications 
of  the  bronchioles  when  inhaled  in 
the  form  of  a  fine  dust.  Watanabe 
and  others  have  shown  that  no  matter 
how  the  bacillus  reaches  the  vesicular 

structure  or  the  smaller  bronchioles,  a  catarrhal  inflammation  results. 
At  first  this  inflammation  partakes  of  the  character  of  an  ordinary 
catarrhal  process  associated  with  desquamation  of  the  epithelium  and 
with  accumulation  of  the  catarrhal  products  in  the  vesicle,  infundibulum. 
and  smaller  bronchiole.  Within  this  inflammatory  collection,  growth 
of  the  tubercle  bacilli  is  favored;  instead  of  the  catarrhal  accumulation 
undergoing  the  usual  softening  and  expulsion,  caseation  results,  due 
to  the  specific  action  of  the  product  of  the  tubercle  bacillus.  The 
progress  that  the  change  makes  must  depend  largely  upon  the  virulence 
of  the  organism  and  upon  the  susceptibility  of  the  individual.  It  is 
probable  that,  with   a   high   degree  of   immunity,  the  bacillus  may  at 


^^v  c-^ 


Fig.  302. — Tuberculous  Pneumonia.  The  Des- 
quamative Lesion WiTHi.N  the  Air-vesicles, 
Which  Occurs  Near  to  and  Around  Titber- 
cles  in  the  Lung,  or  Results  from  the  De- 
posit OF  THE  Tubercle  Bacillus  in  the  .\ir- 
VESICLES. — (Schmaiis.)     X  250  diameters. 

(1,  a.  Exudate  undergoing  degenerative  changes 
(ca-seation)  in  the  air-vesicle.  /'.  Round  cells 
in  same.  c.  Desquamating  cells.  The  inter- 
vcsicular  walls  are  thickened. 


sermann.  "Berl.  klin.  Woch.,"  Nov.  2S.   1904.     Osier, 
Feb.,  IQ05.     Von  Ruck,  "N.  Y.  Med.  Jour.,"  March  11, 
tralbl.  f.  allg.    Path.  u.  path.  Anat.,"  April    15,    1905. 
British  Congress  on  Tuberculosis."   1901,  vol.  iii. 

'See  p.    144;    al'so   Morbiil   Aiintrjmv  tjf  Tuberculosis 


Brooklyn   Mc<l.  Jour.." 

1905.     Sthwarz,  "Cen- 

Ophuls,  "Trans,  ai   th<- 

]>.    14')- 


6i6 


SPECIAL   PATHOLOGY. 


once  be  destroyed,  and  that  the  bacterial  invasion  of  the  vesicular  wall 
may  be  arrested  by  the  protective  forces  of  the  tissues. 

When  infection  through  the  bronchi  occurs,  as  just  indicated,  it 
is  not  necessary  to  presuppose  any  antecedent  lesion.  In  a  small  per- 
centage of  cases,  however,  a  bronchopneumonia,  not  of  tuberculous  origin, 
is  infected  by  the  tubercle  bacillus.  The  result  is  essentially  the  same 
as  though  the  lesion  had  been  tuberculous  from  the  start.  Under  favor- 
able circumstances  the  inflammation  is  restricted  to  a  small  area  of 
pulmonary  tissue.  The  solidified  nodule,  commonly  small,  undergoes 
caseation  and  encapsulation  by  a  wall  of  fibrous  tissue,  into  which  lime 
salts    may    be    infiltrated.     This    constitutes    the    so-called    quiescent, 


■/•*• 


,*» 


m 

w^ 


^-i  t<*if>:*l.\L  '&1m£^  S^Je^ 


*v' 


%% 


y 


y:  1 


W^v^l^^ 


fit/ 


,^%^^i 


i'i.'-^j 


'/^] 


Fig.  303. — Lung,  Chronic  Caseous  and  Ulcerating  Tuberculosis  of  the  Apex;    Tuberculous  Bron- 
chitis, AND  A  Miliary  Tuberculosis. 

"  healed-in,"  or  cretaceous  tubercle,  and  is  what  the  older  writers  spoke  of 
as  chronic  or  caseous  catarrhal  pneumonia.  With  less  evident  resistance, 
or  with  more  virulent  infection,  involvement  of  the  bronchioles  and 
of  adjacent  vesicular  structures  occurs.  This  is  commonly  preceded  by 
more  or  less  leukocytic  invasion  and  proliferative  change,  which  later 
terminate  in  necrosis  and  caseation.  The  process  more  or  less  rapidly 
involves  the  whole  of  the  lobule  in  which  the  original  infection  occurred. 
When  a  lobule  or  part  of  a  lobule  has  been  infected,  the  area  may  be 
enlarged  by  the  coalescence  of  adjacent  lobules  simultaneously  involved, 
or  it  may  extend  from  one  lobule  to  another. 

The  gross  lesion  resulting  from  such  infection  must  vary.     As  a 


ORGAN'S   OF   RKSPIKATION'.  617 

rule,  in  adults  the  structural  chan.ijo  invcjlves  to  a  greater  extent,  and 
is  most  conspicuous  in.  the  apex,  although  the  lower  lobes  may  also 
suffer.  The  point  in  the  apex  usually  affecte<l  is  from  two  to  five  centi- 
meters below  the  superior  border.  Of  the  many  explanations  that  have 
been  advanced  for  the  well-known  frequency  with  which  the  apex  is 
attacked,  none  is  fully  satisfactory.  It  is  probable  that  the  more  active 
circulation  and  freer  movement  of  the  lower  part  of  the  lung  may  better 
enable  the  organ  to  ex[)el  the  infectious  material,  and,  by  reason  of  its 
abundant  blood  supply,  to  resist  infection.  The  lessened  pulmonary 
movement  at  the  apex  offers  better  opj^ortunities  for  the  deposit  of 
infectious  material  on  the  bronchial  surfaces.  Aufrecht  and,  more  re- 
cently, Wassermann  have  suggested  that  the  frequent  involvement  of 
the  apices  is  due  to  the  entrance  of  bacilli  by  way  of  the  tonsils,  pharynx, 
cervical  lymph-nodes,  and  pleura.  Aufrecht  believes  that  the  peri- 
bronchial nodes  are  infected  from  the  cervical  chain  and  that  in  this 
wav  the  lung  is  reached.  It  is  well  known  that  even  in  minor  lesions 
of  the  apex  adhesions  to  the  vault  of  the  pleura  are  frequently  present, 
and  Wassermann  construes  this  to  be  an  evidence  of  direct  infection 
of  the  lung  from  the  cervical  lymphatics.  In  adults  involvement  of 
the  lower  lobes  is  usually  indicative  of  a  primary  lesion  higher  in  the 
lung,  from  which  the  infected  material  has  been  aspirated  into  the 
more  dependent  portions. 

In  many  instances  of  pneumatogenous  tuberculosis  the  process  re- 
mains local,  with  the  development  of  fibrous  tissue  in  the  surrounding 
structures,  to  which  reference  has  already  been  made.  In  other  cases 
the  initial  infection  must  have  involved  a  number  of  areas  in  the  pul- 
monarv  tissue,  or  a  primary  infection  may  have  been  followed  by  ex- 
tension to  adjacent  lobules.  These  recognized  differences  possibly 
justify  the  terms  (i)  localized,  restricted,  or  chronic  piieiiniatogoioits  or 
broiiciiogoiic  tuberculosis;  and  (2)  disseminated,  bronchogenic ,  tuberculous 
pneumonia.  The  symptomatology  of  the  conditions  is  vastly  different, 
largely  because  of  the  greater  amount  of  pulmonary  tissue  involved 
in  the  last-named  process,  but  pathologically  there  is  little  difference 
except  that  due  to  the  fact  that  the  sudden  appearance  of  a  multitude 
of  lesions  must  be  taken  as  an  evidence  of  weak  resistance,  and  as  this 
must  of  necessity  further  lessen  the  protective  powers,  the  disease  not 
uncommonly  runs  a  rapid  course. 

With  the  inception  of  the  initial  lesion  of  tuberculosis  in  the  pul- 
monary tissue, — if  Wassermann's  views  are  correct,  the  primary  infection 
being  lymphatic, — extension  to  adjacent  intervesicular  and  interlobular 
structures  occurs  by  means  of  the  lymph  paths,  constituting  a  form 
of  lymphogenous  or  lymplwgenic  tuberculosis.  Thus,  in  many  areas  of 
purely  bronchogenic  tuberculosis  of  the  kind  described  in  the  foregoing 
paragraphs,  it  is  quite  easy  to  recognize  that  the  extension  is  taking  place 
by  means  of  the  adjacent  lymphatics.  This  view  is  further  supported 
by  the  fact  that  the  lymph  paths  through  the  pulmonary  tis.sue  are 
followed,  and  that,  either  primarily  or  secondarily,  the  lymph-nodes 
are  eventually  affected.  Involvement  of  a  lymphatic  lying  close  to  a 
blood-vessel,  pulmonary  artery,  or  vein  may  be  followed  by  extension 
into  the  vessel-wall,  which  later  becomes  caseous.  In  the  vessel  may 
be  formed  a  thrombus  in  which  caseation  occurs,  followed  by  the  escape 
of  infectious  material  into  the  blood  stream.     If  the  blood-vessel  in- 


6l8  SPECIAL  PATHOLOGY. 

volved  be  small,  and  the  blood  current  be  toward  the  periphery,  as 
would  be  the  case  in  the  branches  of  the  pulmonary  arter}',  there  is 
brought  about  a  circumscribed  hematogenous  miliary  tuherc^ilosis .  In 
other  cases  the  infection  of  the  pulmonary  tissue  through  the  blood 
stream  is  more  uniform,  as  the  result  of  a  wider  and  more  general  dis- 
tribution of  the  tubercle  bacilli  deposited  from  the  circulating  blood. 
In  the  circumscribed  hematogenous  tuberculosis  one  lung  or  a  part 
of  a  lung  may  be  involved,  while  in  the  general  or  diffuse  hematogenous 
(miliary)  tuberculosis  there  is  usually  a  more  or  less  uniform  involve- 
ment of  both  lungs.  Although  it  is  the  general  belief  that  pulmonary 
tuberculosis  is  an  aerogenous  infection,  the  view  is  not  without  opposi- 
tion. Ribbert  and  Baumgarten  are  ardent  advocates  of  hematogenous 
infection,  and  the  latter  has  been  able  to  produce  strictly  localized 
pulmonary  tuberculosis  by  infecting  animals  through  the  urethral 
mucosa.  Aufrecht  also  inclines  to  the  hematogenous  origin  of  many 
cases.  Woodhead  strongly  insists  on  the  presence  of  some  primary 
focus,  usually  catarrhal,  on  which  the  tubercle  bacillus  is  engrafted. 
From  such  points  of  infection  local  dissemination  occurs  through  the 
lymphatics.  Abrikossoff  thinks  that  the  lesion  begins  as  a  peribronchial 
tuberculous  lymphangitis  which  extends  along  the  wall  of  the  bronchi. 
As  a  result  of  caseation  the  bronchial  wall  is  opened  and  the  caseous 
material  aspirated  into  other  parts  of  the  organ,  causing  areas  of  broncho- 
pneumonia which  progress  to  caseation.  In  the  completely  evolved 
tuberculosis  of  pulmonary  tissue,  bronchogenous,  lymphogenous,  and 
hematogenous  distribution  of  the  organism  may  often  be  implicated. 

Morbid  Anatomy. — There  is  probably  no  other  well-known  affection 
of  the  lung  associated  with  more  diversity  in  the  gross  lesions,  and  yet 
due,  in  all  its  forms,  to  the  same  cause.  In  some  of  the  cases  it  may 
be  possible  to  formulate  an  opinion  as  to  the  method  by  which  infec- 
tion occurred.  In  other  cases  this  is  quite  impossible.  Usually,  it  is 
said  that,  anatomically,  tuberculosis  of  the  lung  manifests  itself  in 
three  forms :  (i)  An  acute  mihary  tuberculosis,  also  called  acute  phthisis, 
or  galloping  consumption;  (2)  chronic  ulcerating  or  caseous  tuberculosis; 
(3)  fibroid  phthisis. 

The  morbid  anatomy  of  acute  miliary  tuberculosis  of  the  lung  must 
depend  upon  the  extent  and  duration  of  the  tuberculous  process; 
organs  in  which  there  has  been  a  wide-spread  distribution  of  a  large 
number  of  tubercles  do  not  manifest  the  same  changes  as  those  in 
which  the  eruption  involves  a  more  restricted  area  and  gives  rise  to 
fewer  tubercles.  Sometimes  the  large  number  of  tubercles,  with  the 
associated  proliferative  changes,  may  almost  as  fully  solidify  a  lung 
as  does  croupous  pneumonia  and,  both  cHnically  and  pathologically,  the 
organs  may  closely  resemble  each  other.  If  the  process  has  existed 
for  even  a  comparatively  short  time,  the  miliary  tubercles  become 
sufficiently  large  to  be  readily  recognized,  and,  of  course,  as  soon  as 
this  occurs  the  anatomic  diagnosis  is  easily  made.  The  lung  is  more 
voluminous  than  normal,  and  does  not  collapse  with  its  wonted  readi- 
ness. The  pleura  is  frequently  the  seat  of  an  old  inflammation,  and 
not  uncommonly  shows  uniform  adhesion  between  the  visceral  and 
parietal  layers.  Small  tubercles  may  be  seen  in  the  pleura  or  just  be- 
neath, or,  what  is  more  common,  they  are  palpable.  On  incision, 
the  lung  usually  cuts  with  more  resistance  than  normal.     The  amount 


ORGANS  OF  RESPIRATION. 


619 


of  moisture  is  dependent  upon  tlie  presence  of  an  associated  edema,  in- 
tense congestion,  or  hyperemia.  The  recognizable  tubercles  are  usually 
paler  than  the  surrounding  lung  tissue,  and  are  white,  grayish-white, 
or  yellow  in  ciolor.' 

With  the  acute  lesion,  evidences  of  older  tuberculosis,  such  as  healed- 
in  areas,  areas  of  caseation  and  fibrosis,  or  fully  formed  cavities,  may 
be  present.  It  may  be  possible  to  demonstrate  the  primary  nodule 
from  which  infection  has  occurred,  although  in  the  large  majority  of 
cases  the  demonstration  will  l)e  unsatisfactory,  and  seldom  conclusive. 


^x:.  'v^v 


r< 


I'iC.    304. — Tt'BEBCTLOSIS  OF   THE    LVXO. 

Ti>suc  ti-xcil  in  cr'iro^ivi-  sulilimaic.  infiltrated  with  paraffin,  stained  with  hematoxylin  jnd  cnsin,  and  mounted  in 
bal.<^m.  ii.  Tulx-rde  with  advanced  cascati<jn.  6  and  c.  'ruherclos  showing  less  ailvanced  dcnencrative 
changes.  In  the  upper  ,ind  right  quadrant  of  b  is  seen  a  giant  cell.  d.  Three  air-vesicles  p-inly  fil!,-.)  V.y  in 
flammatory  products,  tulierculous  pneumonia.    (J-inch  objective,  i-inch  ocular.) 

An  examination  of  the  lung  during  the  period  in  which  the  tuin-n  its 
are  forming,  or  when  they  are  fully  formed,  will  result  in  the  recog- 
nition of  histologic  changes  such  as  are  shown  in  figure  84,  page  151. 
(See  also  Fig.  305.)  In  acute  cases  there  is  usually  considerable  catar- 
rhal pneumonia  or  intravesicular  exudate,  and  sometimes  this  may  be 
fibrinous,  further  explaining  the  gross  resemblance  of  the  lesion  t<>  t  fUD- 
ous  pneumonia. 

'See  Tuberculosis.  \-.    >44.   also  Morbid  Anatomy  of  Tuberculobi-.  j.    .  »' 


620  SPECIAL  PATHOLOGY. 

Morbid  Anatomy  of  the  Chronic  Ulcerating,  Ulcerative,  or  Caseous 
Tuberculosis  of  the  Lung. — This  is  a  type  of  the  disease  that  usually 
follows  aerogenous  infection.  The  structural  changes  are  commonly 
situated  in  the  apex,  although  other  parts  of  the  lung  may  be 
involved.  The  lesion  consists  for  the  most  part  of  caseous  areas,  vary- 
ing in  size  from  purelv  microscopic  bodies  (miliary  tubercles)  to  cavities 
from  five  to  ten  centimeters  in  diameter,  or  much  larger.  The  cavity 
formation  is  brought  about  by  caseation  and  confluence  of  a  large 
number  of  tubercles,  with  an  associated  bronchopneumonia,  which  it- 
self becomes  caseous,  and  is,  of  course,  due  to  the  tuberculous  infection 
of  the  pulmonary  tissue.  As  these  areas  of  caseation  are  increased  in 
size  by  peripheral  extension  and  coalescence,  obliterative  changes  take 
place  in  the  blood-vessels,  the  vesicular  walls  and  fibrous  septa  disappear 
before  the  extending  necrosis,  the  pulmonary  tissue  itself  becomes 
caseous,  and  eventually  the  necrotic  collection  ruptures  into  a  bronchus. 
With  evacuation  of  the  caseous  contents  a  cavity  is  formed.  The 
wall  of  such  a  cavity  is  lined  by  a  layer  of  necrotic  and  caseating  pul- 
monary tissue  containing  tubercles  in  various  stages  of  caseation,  and 
the  inflammatory  products  that  usually  accompany  infection  by  the 
tubercle  bacillus.  External  to  the  caseous  layer  is  a  wall  of  granula- 
tion tissue  composed  largely  of  lymphoid  cells,  and  usually  containing 
easily  recognizable  tubercles.  Outside  of  the  zone  of  granulation  tissue  is 
a  variable  amount  of  fibrous  tissue.  In  chronic  cases  cavities  of  long 
duration  are  sometimes  surrounded  by  a  fibrous  membrane  the  inner 
surface  of  which  may  be  smooth  or  granular,  usually  the  latter.  Such 
excavations  resemble  dilated  bronchi,  and  the  two  may  be  present  in 
the  same  organ.  The  points  assisting  in  differentiating  the  two  cavities 
have  been  mentioned  on  p.  580. 

The  most  disastrous  changes  in  pulmonary  tuberculosis  result  from 
secondary  infection  by  pyogenic  organisms.  Ophiils  found  that  in  twenty 
of  thirty-nine  cases  of  pulmonary  tuberculosis,  acute  mixed  infection. 
or  sepsis,  seemed  to  be  the  immediate  cause  of  death.  He  has  not  been 
able  to  corroborate  the  observations  of  those  who  maintain  that  the 
softening  observed  in  tuberculous  lesions  is  invariably  due  to  mixed 
infection.  Comparative  pathology  shows  that  in  the  lower  animals, 
particularly  cattle,  rapid  and  extensive  necrosis  is  usually  due  to  con- 
current pyococcic  invasion  of  the  tuberculous  tissue.  In  such  cases 
and  in  man  the  bacteria  accompanying  the  tubercle  bacillus  in  the 
lesions  are  the  ordinary  pyogenic  cocci,  the  pneumococcus,  tetracoccus, 
colon  bacillus,  and  occasionally  other  microbes,  all  of  which  may  not 
be  pyogenic.  Whether  or  not'such  organisms  find  ready  access  to  the 
caseous  area  before  its  rupture  into  the  bronchial  wall,  their  introduction 
is  assured  at  this  time,  and  hence  there  are  added  to  the  tuberculous 
process,  properly  so  called,  active  pyogenesis  and  the  absorption  of 
the  products  of  pyogenic  bacteria.  The  progressive  extension  of  case- 
ous tuberculosis  "is  favored  by  the  occurrence  of  mixed  infection. 
Necrotic  changes  in  the  contiguous  tissue  and  involvement  of  the  ad- 
jacent lymphatics  may  progress  slowly.  In  other  instances  there  is  a 
more  rapid  extension, 'and,  after  a  comparatively  short  period  of  cavity 
formation,  invasion  of  a  blood-vessel  or  prominent  lymph  canal  occurs, 
or  the  process  extends  to  other  parts  of  the  lung,  and  leads  to  the  rapid 
dissemination  of  infection  and  to  death. 


OKC.ANS  OF   RESPIRATION. 


621 


Morbid  Auatomy  of  Fibroid  Phthisis. — The  term  fibroid  plithisis  is 
applied  to  tuberculous  processes  involving  a  lung  where  the  tendency 
is  toward  fibrosis,  restriction,  limitation,  and  healing-in,  and  where 
necrosis,  degeneration,  and  extension  are  limited  by  the  protective 
powers  of  the  tissues  or  are  rendered  less  extensive  by  reason  of  reduced 


F 


/_ 


Fjc.  30s. — LrxG,  Chronic  I'lcxrative  Tuberculosis  of  Upper  Lobe;  Accte  Miijarv  Tcberci-losis  as  a 
Terminal  Lesion  Lvvolmno  the  Entire  Organ;  Slight  Interstitial  (Fibroid)  Pneimonia;  Chronic 
TtTBERciLois  Peribronchitis;  Bronchiectasis;  Actte  Psevdomembranois  Bronchitis;  Chronic 
Fibrohyaloplevritis. 

A.  A.  Ca\ities.  B.  B.  I>iLit«l  bronchi.  C.  Miliary  tubercles,  many  of  which  arc  conspicuous,  csprcially  in  the 
liiwcr  lol)e.  D-  .Area  of  hemorrhage.  £.  Two  bronchi  containing  casts.  F.  Brondius,  the  wall  of  which  is 
greatly  thickened  by  a  tuberculous  peribronchitis. 


virulence  of  the  infecting  organism.  In  typical  cases  a  comparatively 
small  area  of  the  lung  is  involved.  In  the  purely  tuberculous  lesion 
a  large  portion  of  the  organ  may  show  the  changes  of  fibroid  pneumonia, 
and  contain  only  a  small  amount  of  caseous  tissue.  In  other  cases  the 
evidence  of   tul)erculosis,  at  present   active  or  quiescent,   may   be  ir- 


622  SPECIAL  PATHOLOGY. 

regularly  distributed  through  a  large  part  of  the  pulmonary  tissue. 
In  typical  cases  the  evidence  indicates  that  tuberculosis  is  being  limited 
or  restricted  by  fibroid  and  calcareous  changes;  in  other  words,  that 
healing-in  is  progressing.  In  patients  dying  from  other  causes  small 
areas  are  not  infrequently  found  in  which  the  tuberculous  process  has 
been  fully  restricted  or  walled  off  by  masses  of  fibrous  tissue,  or  limited 
by  calcareous  infiltration.     (See  Quiescent  Tuberculosis,  p.    151.) 

Mixed  Forms  of  Pulmonary  Tuberculosis. — In  a  large  percentage  of 
the  cases  of  tuberculosis  of  the  lung,  as  observed  postmortem,  the  disease 
is  manifested  by  mixed  lesions,  due  to  the  presence  of  more  than  one 
form  of  tuberculosis,  as  described  in  the  foregoing  pages.     There  is  not 


Fig.  306.— Wall  of  a  Tuberculous  Cwn^.—iSchmaus.)    X  loo  diameters. 
c    Ca\-itv.    f,,  fii.  Smaller  cavities  that  will,  eventually,  as  the  result  of  caseation  and  liquefaction  of  the  interven- 
ing tissue,  blend  with  the  larger  caWty.    b,  b.  Remains  of  a  bronchi,    t,  t.  Tubercles  undergoing  softemng.    Just 
over  a  are  shown  other  tubercles,    k.  Caseous  wall.     g.  Blood-vessel. 

infrequently  a  distinct  area  in  which  the  lesion  is  old  and  cretaceous. 
Around  this,  at  times  some  distance  from  it,  can  be  recognized  a  more 
recent  and  active  tuberculosis,  with  cavity  formation,  and  corresponding 
to  the  anatomic  subdivision — chronic  caseous  tuberculosis.  Still  other 
parts  of  the  lung  may  show  the  changes  of  a  typic  acute  miliary  tuber- 
culosis. 

Tuberculosis  of  the  lung  in  all  its  forms  is  practically  always  as- 
sociated with  some  lesion  of  the  overlying  pleura,  which  may  be  a  frank, 
acute  pleuritis^  or  chronic  sclerotic  change.     Frequently  the  cavity  of 
1  See  Inflammations  of  the  Serous  Membranes,  p.  475. 


ORGAN'S  OF   RKSPIRATION'.  62^^ 

the  pleura  has  been  obliterated  by  universal  adhesions  and  often  the 
serosa  is  enorniously  thickened  (chronic  hyj)erplastic  hyaloserositis). 

Syphilis  of  the  lung'  occurs  in  both  the  cojiiictiital  and  acquired  forms 
of  the  disease.  In  the  former  a  condition  known  as  ichitc  hepatization 
is  occasionally  seen;  proliferation  of  the  cells  that  line  the  fetal  ves- 
icles and  of  the  connective  tissue  of  the  septa  leads  to  the  oblitera- 
tion of  the  air-spaces,  and  when,  at  birth,  the  inspired  air  enters  the 
lung,  none  gains  ingress  to  the  affected  area;  the  only  circulation  to 
this  part  is  that  for  supplying  nourishment;  hence,  the  area  is  pale, 
anemic,  and  is  said  to  show  'd.'hitc  hcpatizatioi,  the  paleness  contrast- 
ing with  the  surrounding  hyperemic  area.  Another  manifestation  of 
transmitted  syphilis  is  the  ordinary  gumma.  This  may  be  found  in 
any  part  of  the  lung,  but  is  usually  near  the  larger  bronchi  at  the  hilum. 
The  gummata  are  for  the  most  part  small,  but  they  may  attain  diam- 
eters of  from  two  to  six  centimeters.  Gummata  of  the  lung  in  con- 
genital syphilis  are  of  infrequent  occurrence,  but  when  fully  developed, 
thev  do  not  differ  essentially  from  those  found  in  the  acquired  di.sease. 

In  acquired  syphilis  gummata  are  more  frequent;  the  situation  is 
usually  at  the  root  of  the  lung,  but  they  may  be  anywhere.  They 
are  grav  or  grayish-yellow,  not  uncommonly  caseous,  and  surrounded 
by  a  fibrous  capsule,  which,  if  recent,  is  translucent;  if  older,  is  firm, 
truly  hbroid,  and  dense.  Like  all  the  infective  granulation  tumors, 
these  begin  in  the  alveolar  walls  or  in  the  walls  of  the  bronchi,  beneath 
the  basement  membrane;  after  the  aggregation  of  cellular  elements 
hyaline  degeneration  and  necrosis  ensue,  and  eventually  caseation  com- 
pletes the  process,  and  evacuation  into  a  bronchus  commonly  follows. 

Occasionally,  an  interstitial  pneumonia  accompanies  the  formation 
of  the  gumma,  and  Virchow  believed  that  a  purely  syphilitic  process 
may  begin  as  an  interstitial  inflammation  at  the  root  of  the  lung  and 
extend  along  the  course  of  the  interlobar  and  the  interlobular  septa, 
particularly  the  latter.  When  marked,  it  maybe  attended  by  bronchi- 
ectasis and  all  the  usual  phenomena  of  interstitial  pneumonia.  In 
many  cases  of  acquired  pulmonary  syphilis  a  catarrhal  inflammation 
involving  the  bronchi  and  vesicles  accompanies  the  interstitial  fibroid 
hyperplasia  or  the  formation  of  gummata.  The  clinical  and  even  the 
anatomic  changes  may  resemble  tuberculosis  so  closely  that  nothing 
short  of  demonstrating  the  tubercle  bacillus  can  enable  the  observer  to 
identify  the  process.  As  syphilitics  may  become  tuberculous  and 
patients  with  tuberculosis  may  acquire  syphilis,  the  affections  may  be 
concurrent  in  tlie  lung. 

Leprosy  of  the  lung  may  occur  as  a  distinctly  miliary  process,  the 
leprous  nodules  so  closely  resembling  those  of  tuberculosis  that  many 
claim  the  determining  factor  is  a  tuberculous  infection  of  a  leprous  in- 
dividual; the  almost  utter  impossibility  of  differentiating  the  lesions 
has  led  a  few  to  believe  that  leprosy  was  but  a  form  of  tuberculosis; 
evidence  confirmatory  of  this  view  is  not  in  the  least  conclusive,  and  for 

'  Flockemann,  "Centralbl.f.  Path.  u. path.  Anat..  "  1S99.  Bd.  x,  p.  449.  "  Xoth- 
nagel's  Encyclopedia  of  Practical  Medicine."  American  edition,  article  on  "Syphi- 
litic Pneumonia."  vol.  on  "Diseases  of  the  Bronchi.  Pleura,  and  Lungs,"  1903, 
p.  643.  Winfield.  "Med.  News,"  Aug.  30,  1902.  p.  405.  Hansemann.  "Cen- 
tralbL  f.  med.  Wiss.,"  Julv  3.  1902.  Berg.  "Med.  Record."  Dec.  13,  1902,  p- 
926.  Remsen,  "Bull,  of  Johns  Hopkins  Hosp.,"  Oct..  1903,  p.  280.  Willson, 
"Med.  News,"  Feb.  25.  1905,  p.  351. 


624  SPECIAL  PATHOLOGY. 

the  present  there  seems  to  be  no  reason  for  believing  that  the  two  dis- 
eases are  in  any  way  related. 

Glanders  of' the  lung^  may  arise  as  the  result  of  aspiration  of  the 
bacilli  from  lesions  in  the  upper  passage,  or,  as  in  acute  glanders,  the 
infection  may  occur  by  the  blood  stream.  Once  localized  in  the  lung 
tissue,  whether  interstitial  or  intravesicular,  a  more  or  less  severe 
bronchopneumonia  is  brought  about,  and  frequently  this  proves  fatal. 
When  time  is  afforded,  the  typical  glanders  nodules  develop.  These 
lie,  as  a  rule,  immediately  under  the  pleura,  and  present  somewhat 
different  aspects  at  different  stages  of  their  development.  At  first 
they  are  gray,  slightly  translucent,  and  much  softer  than  tubercles; 
later  they  become  somewhat  denser,  and  a  hyaline  change  occurs  in  the 
center,  the  process  eventually  terminating  in  a  caseous-like,  encapsulated 
mass,  especiallv  if  the  lesion  be  restricted  to  one  or  two  points  of  infec- 
tion in  an  animal  not  very  susceptible  to  the  disease.  In  the  horse,  in 
which  animal  susceptibility  is  marked,  and  occasionally  in  man,  the  con- 
dition terminates  in  a  suppurative  pneumonia  by  pyogenic  infection  of 
the  glanders  nodules. 

Actinomycosis  of  the  lung-  results,  in  most  cases,  from  infected 
material  reaching  the  involved  part  through  the  air-passages ;  a  bronchial 
inflammation  accompanies  the  fungus  down  into  the  lobules,  where  a 
so-called  miliary  bronchopneumonia  ensues;  the  number  of  these 
areas  is  dependent  upon  the  number  and  dissemination  of  the  fungi. 
A  mass  of  granulation  tissue  develops  around  the  point  of  infection, 
m  which  also  occur  characteristic  groups  of  fungi.  Suppuration  and 
not  uncommonly  cavity  formation  ensue;  it  is  usually  conceded  that 
the  rav  fungus  i's  itself  pyogenic,  and  can,  therefore,  induce  pus-forma- 
tion without  the  intervention  of  the  cocci  of  suppuration.  When  the 
actinomycotic  lesion  approaches  the  surface,  an  adhesive  pleurisy  usually 
results,  and  progresses  to  obHteration  of  the  cavity.  In  many  of  the 
reported  cases  the  suppurative  process  penetrated  the  chest-wall  and 
the  diagnosis  was  made  by  finding  the  characteristic  granules  in  the 
discharge.  Mediastinal  actinomycosis  may  or  may  not  accompany  the 
pulmonary  form,  or  the  one  may  be  secondary  to  the  other.  Occasion- 
ally, actinomycotic  fibroid  changes  in  the  lung  and  "healing-in"  of 
the  infected  area  occur.  In  such  cases  the  masses  found  postmortem 
are  surrounded  by  a  dense  fibrous  and  calcareous  capsule.  The 
diagnosis  of  actinomycosis,  both  clinical  and  pathologic,  is  dependent 
upon  finding  the  fungus  in  the  sputum  during  life  or  in  the  masses  post- 
mortem. Forms  of  actinomycotic  bronchitis  and  peribronchitis  have 
been  described. 

Tumors  of  the  lungs^  are  rarely  primary;     usually  they  arise  by 

1  MacCallum,  "  Ziegler's  Beitr.,"  1902,  Bd.  xxxi,  p.  440.  See  also  Glanders, 
p.  160. 

2  Spijariny,  abstract  in  "Med.  Record,"  April  11,  1903,  p.  576.  Webber, 
"Brit.  Med.  Jour.,"  May  9,  1903,  p.  1084.  See  also  "Pulmonary  Streptothn- 
cosis,"  "Warthin  and  Olne'v."  Amer.  Jour,  of  Med.  Sci.,"  Oct.,  1904,  p.  637.  Maass, 
"Annals  of  Surgery,"  Aug.,  1903,  p.  292.     Also  consult  Actinomycosis,  p.  166. 

3  Pollack,  "Virchow's  Arch.,"  1901,  Bd.  175,  p.  129.  Musser,  "Univ.  of 
Penna.   Med.   Bull.,"    1903.      Ramond  and  Boidin,   "La  Presse  Med.,"  Jan.    14, 

1903,  p.  56.  Rolleston  and  Trevor,  "Brit.  Med.  Jour.,"  Feb.  14,  1903,  p.  361. 
Demorest,  "Med.  Record,"  Jan.  16,  1904,  p.  96.  Bremken,  "Amer.  Jour,  of  Med. 
Sci    "    Dec,  1903.     Adler,  Carpenter  Lecture,  N.  Y.  Acad,  of  Medicine,  Oct.  20, 

1904.  Broc,  "C.  R.  deSoc.  Anat.,"  Jan.  27,  1905.  Packard,  "Med.  News,"  Feb. 
18,  1905,  p.  303. 


ORGANS  OF   RESPIRATION.  625 

metastasis  from  t)tlier  organs  or  by  invasion  from  adjacent  structures. 
According  to  Adler.  Wolff  observed  46  primary  tumors  of  the  lung  in 
20,160  autopsies.     Adler  collated   330  cases  of  lung  tumor;    211    were 
cancers,  22  sarcomata,  and  24  endotheliomata;     10  were  mixed  tumors 
and  the  remainder  unclassified.     Occasionally  the  {jre.sence  of  pulmon- 
ary  neoplasms   may   be   diagnosed   by   the   examination   of   fragments 
found  in  the  expectoration;    in  discussing  Broc's  case,  Cornil  referred 
to  such  an  instance,  and  Demorest  also  records  a  case  in  which  the  diag- 
nosis was  made  from  the  sputum.      Non-malignant  e])ithelial  tumors 
of  the  lung  are  exceedingly  rare,  although  adenomata  of  the  bronchial 
glands  have  been  described.     Embryonic  epithelial  neoplasms  are  not 
correspondinglv  rare:     1  have  seen  four  instances  within  the  last  few 
years.     When  carcinomata  occur  in  the  lung,  as  the  result  of  the  rich 
vascular  supplv  and  the  relatively  small  amount  of  connective  tissue, 
the   neoplasm    is   usually   encephaloid.     The   growth   may   be    circum- 
scribed and  manifest  itself  as  a  few  masses,  or  it  may  consist  of  one 
gray  or  white  soft  nodule.     Each  nodule  may  develop  as  a  single  mass 
without  very  marked  dissemina- 
tion, but  more  commonly  exten-  ^ 
sion  occurs  through  the  lymph-                           /  ""'11^;%^.         "^-^ 
channels,  and  results  in  dissem-                    f?Oi  '   .   ,  ',    '^."      ' 
inated  growths  throughout  the                     ""V|!:;"' .    '':-^^  •  v.<  .      ,    .\.{\ 
lung  tissue.    The  local  metastasis                /iiV'^H'^'v ''/^  *" '^ "^  "^ 


gives  rise  to  nodules  similar  to  ^'^^'''^''^'*^:ti^'^^-''-.i  ^    iy^ii} 

the  original,   which,  by    exten-      ^ ^^'^^^^^*''''  '  ■^^-^^^^^''^ 

sion,  coalesce  and  convert  nearly  it  •  V  •      •  y^ -v'' 

all,  if    not  all,   the  lung  into  a  /o'w**''^--^''^'^^'!  '-^'  "^- 

cancerous    mass.      Invasion    of  '^%'l^'  "''''■*    '',-.;'' 
peribronchial    and     mediastinal  .  '     -' 

Ivmphatics   takes  place,  and   if  -^--''-  ' -^.^j—     / 

not  fatal   bv  this  time,  the  prOC-  Fig.  ^07.— Branch  of  Pdlmonary  Artery  Contai.vinc. 

occ  ma\-  Av'tPnrl    tn   thp   nnno<;itp  Sarcoma  Cells  from  a  Case  of  Wide-spread  Dis- 

eSS  ma}    extena    lO    Xne    opposite  sExnNA-noN  of  a  Timor   Primary  in  the  Slbcu- 

Ortran.  tankoi-s  Tissue  of  the  Thigh. 

Pr-lmar-i-  tiimnrc  nf  thp  nrllllt  -^  •  Sarcoma  cells.    5.  Polymorphonuclear  k-ukocyte.  There 

rnmar\    tumors  OI   l  ne  aaUU  -^  ^^^  irreRuhirily  in  the  size  and  shape  of  the  red  cells 

connective-tissue    series    are    less  <luf  to  •''«;  ass<Ki.ite<l  secondary  anemia. 

frequent.     Fibroma,  chondroma, 

osteoma,  and  mixed  forms  of  these,  with,  rarely,  a  small  quantity  of 
lipomatons  tissue,  have  been  described.  They  are  commonly  multiple; 
usually,  a  number  are  to  be  found  disseminated  throughout  one  or 
both  lungs. 

Embrvonic  connective-tissue  neoplasms  (sarcomata)  are  infrequent 
primary  tumors  of  the  lung.  The  form  of  sarcoma  known  as  ciido- 
thclioma,  arising  in  or  from  the  pleura,  is  the  most  common.  Like 
the  cancers,  such  tumors  usually  form  single  large  masses,  but  may 
extend  to  the  lymph -nodes  and  mediastinal  tissues.  As  a  rule,  primary 
sarcoma  is  restricted  to  one  lung. 

Secondarv  tumors  of  the  lung  arise  as  the  result  of  inva.sion  through 
the  Ivmphatics  or  the  blood;  even  the  instances  of  apparently  direct 
invasion  are  not  truly  so.  The  embryonic  epithelial  tumors — the  can- 
cers— invade  the  lung,  as  secondary  growths,  in  a  very  small  percent- 
age of  the  cases  of  carcinoma  elsewhere.  The  epitheliomata  rarely,  if 
ever,  the  scirrhus  more  commonly,  and  the  encephaloid  most  frequently, 

41 


626  SPECIAL  PATHOLOGY. 

occur  as  secondary  growths  in  the  lung.  The  cancers,  spreading  by 
the  lymphatics,  usually  involve  those  structures  in  the  lung  first,  and 
manifest  dissemination  along  the  course  of  the  lymph -channels. 
Reaching  the  pleura  by  the  lymphatic  system,  dissemination  may  occur 
along  the  course  of  the  interlobular  lymph-vessels,  in  which  will  be  seen 
the  grayish  cancerous  lines  traversing  the  connective-tissue  septa,  and 
even  extending  to  the  peribronchial  lymph-nodes. 

Carcinoma  occasionally  reaches  the  lung  by  the  blood,  and  the 
frequency  with  which  this  is  associated  with  an  initial  focus  in  the 
digestive  organs,  more  especially  that  part  of  the  alimentary  canal 
that  communicates  with  the  chyle  duct,  apparently  explains  this  form 
of  dissemination;  in  reality,  the  cancer  cells  have  reached  the  blood 
by  being  poured  into  the  venous  circulation  through  the  lymph-chan- 


FiG.  308. — Lung,  Part  OF  Serous  Surface;  Secondary  Sarcoma. 
The  larger  distinctly  elevated  masses  are  the  oldest;    similar  smaller  nodules  are  more  recent,  while  the  youngest 
growths  are  «hown  as  minute  (miliary)  grayish-white  or  white  subserous  dotlets.    The  specimen  is  a  part 
only  of  the  lower  lobe;   reproduction  natural  size.    The  incised  surface  of  the  same  specimen  is  shown  m 
Fig.  309. 

nels  arising  in  the  abdominal  cavity.  When  a  cancerous  embolus 
lodges  in  the  lung,  the  growth  immediately  proceeds  in  the  usual  way; 
as  these  emboli  are  commonly  multiple  and  are  fairly  abundant,  both 
lungs  are  likely  to  be  involved,  and  many  small  tumors  occur  more 
frequently  than  a  single  large  one.  There  can  be  found,  of  course,  no 
regularity  in  their  location,  and,  once  lodged,  they  follow  the  same 
processes  of  growth  and  local  dissemination  that  have  already  been  in- 
dicated ;  the  encephaloid  is  the  carcinoma  most  frequently  reaching  the 
lung  by  metastasis;  encephaloid  cancers  that  have  undergone  colloid 
or  mucoid  change  are  especially  Hable  to  such  dissemination.  Scirrhus 
rarely  involves  the  lung. 

Of  the  secondary  tumors  belonging  to  the  adult  connective-tissue 


ORGANS   OF   RESPIRATION'. 


02  7 


series,  there  are  lourteen  recorded  instances  in  wliich  chondromata  and 
osteomata  have  reached  the  lunj.>^.  By  hematogenous  dissemination  the 
sarcomata  are  the  most  frequent  invaders  of  the  pulmonary  tissues. 
This  is  due  to  the  relation  which  the  cellular  elements  of  these  neoplasms 
bear  to  the  blood  channels  which  they  contain.  The  small  round-cell 
varieties  are  most  commonly  noted,  although  any  form  of  sarcoma  may 
be  disseminated  by  the  blood.  As  to  the  seat  of  the  initial  growth,  it 
is  fountl  that  the  sarcomata  arising  in  bone,  and  especially  in  the  long 
bones,  are  the  most  frequent  as  secondary  growths  in  the  lung.  Mela- 
notic sarcomata  are  also  prone  to  such  metastasis.  Unlike  cancers, 
sarcomata,  if  situated  in  the  distribution  of  the  portal  vein,  rarely  reach 
the  lung,  but,  traveling 
by  the  blood-vessels,  in- 
volve the  liver. 

Parasites  in  the  lung 
and  bronchi  are  not  of 
freciueiit  occurrence. 
Reference  has  already 
been  made  to  the  Dis- 
toma  westermanii,  dis- 
toma  pulmonale,  or 
bronchial  fluke,  as  a 
cause  of  hemoptysis. 
(See  p.  192.)  Ascaris 
lumbricoides  occasion- 
ally migrates  into  the 
air-passages,  and  may 
cause  obstruction  with 
fatal  results;  or,  reach- 
ing the  bronchi,  may  in- 
duce gangrene,  etc.  It 
is  not  uncommon  in  in- 
fested bodies  to  find 
that  the  worm  has  en- 
tered the  air-passages 
postmortem. 

Hydatids '  occur  in 
the  lung;  they  may  be 
central     or    subpleural. 

The  subpleural  form,  and  hydatids  of  the  pleura,  may  occur  together; 
in  either  case  effusion  into  the  pleura  is  usually  found,  and  not  uncom- 
monly empyema  results.  The  cysts  are  multiple  and  commonly  are 
near  the  base;  they  may  be  diaphragmatic.  When  in  the  lung,  the 
compression  resulting  from  their  growth  leads  to  conditions  favorable 
to  infection,  and  abscess  and  gangrene  sometimes  result.  Clinically  and 
pathologically,  a  positive  diagnosis  is  dependent  upon  finding  the  hook- 
lets  in  the  cysts  or  discharges.  (See  p.  1Q9.)  The  parasites  more 
rarely  found  in  the  lung  are  the  Cysticercus  cellulosae,  Strongylus  long- 
evaginatus,  and  Pentastoma  denticulatum.  ^ 

'Pel.  "Berl.  klin.  Woch.,"  Aug.  26,  looi.  Lendon,  "Clinical  Lectures  on 
Diseases  of  the  Lung,"  1002.  Quill,  "Jour,  of  Royal  Army  Med.  Corps,"  April, 
1004.     Symmers,  "Lancet."  Jan.   7,   1005,  p.   22. 


Fig.  309. — Li;n<..  I.sci.sed  Surface  of  Part  of  One  Lobe,  Secondary 
Sarcoma. 
The  serous  surface  is  shown  in  Fig.  308.     (Natural  size.) 


CHAPTER  IX. 
DISEASES  OF  THE  URINARY  ORGANS.^ 

The  Normal  Kidney. — The  kidneys  vary  somewhat  in  size  and  are 
rarely  symmetric;  normally  the  left  kidney  weighs  150  gm.  to  190  gm., 
and  the  right  slightly  less.     According  to  Verraeck,^  the  specific  gravity 


F]G.  310. — LON'GITUDINAL  SECTION  OF  THE  KiDNEY. — (Tysoii,  after  Henk.) 
I.  Cortex,  equal  in  thickness  to  about  one-half  the  length  of  the  medullary  pyramid.  2.  Medulla.  C.  Pelvis, 
with  calices  extending  outward  between  the  papillae  of  the  pyramids,  i'.  Medullary  rays,  between  which 
are  the  labyrinths  i".  2'.  Conducting  tubules  of  the  medulla.  The  line  from  2"  runs  to  a  point  just  below 
the  corticomedullary  line.  A.  Renal  artery:  at  s,  5  is  shown  its  method  of  distribution.  3,  3.  Transverse 
section  of  tubules.     4.  Fat  of  renal  pelvis.     *Transversely  coursing  medullary  rays.     U.  Ureter. 

of  the  organs  varies  between  1.050  and  1.055.     The  pyramid  is  the  ana- 
tomic unit;    the   Malpighian   tuft,  with  its  blood-vessels  and  the  tube 

*  Of  the  more  recent  works  on  diseases  of  the  kidney  the  student  is  advised 
to  consult  Morris,  "Surgical  Diseases  of  the  Kidney  and  Ureter,"  1901,  and  Tyson, 
"Bright's  Disease  and  Diabetes,"   1904. 

^  "  La  Semaine  M6d.,"  Aug.  7,   1901. 

628 


DISEASES  OF  THE   URINARY   ORGAN'S. 


629 


passing  oflf  as  the  proximal  convoluted  tube,  the  loop  of  Henlc.  the 
second  or  distal  convoluted  tube,  and  tcrininating  in  the  conducting 
tube,  constitutes  the  gland  unit. 

Histologically,  the  tubules  are  tracts  of  mucous  membrane  in  which 
different  portions  are  lined  by  epithelial  cells  having  slightly  different 
characters.  The  ei)ithelium  of  the  tuft  is  flat,  with  a  tendency  to  cuboid 
outline;  the  epithelium  of  the  convoluted  tubes  is  more  or  less  poly- 
hedral. The  cortex  of  the  organ  is  made  up  of  two  histologic  struc- 
tures, which  are  most  important  from  a  pathologic  standpoint;  these 
are  the  labyrinth  and  the  medullary  rays  or  pyramids  of  Ferrein.  In  a 
perfectly  normal  kidney  these  two  elements 
can  not  be  satisfactorily  differentiated  by 
the  unaided  eye;  but  with  the  occurrence 
of  inflammation  or  of  marked  degenerative 
change  the  structures  named  are  often 
outlined  with  remarkable  clearness.  The 
thickness  of  the  cortex  varies  considerably 
in  health,  and  also  depends  on  the  size 
and  general  contour  of  the  organ.  A  kid- 
ney may  be  short,  with  a  thick  cortex, 
or  long  and  the  cortical  portion  somewhat 
thinner;  there  is,  however,  a  more  or  less 
definite  relation  between  the  cortex  and 
the  medullary  portion,  which  is  sufficiently 
constant  to  be  utilized  for  comparison.  If 
a  pyramid  be  selected  which  is  incised 
from  apex  to  base,  and  a  line  be  extended 
from  the  apex  of  the  pyramid  to  the 
capsule,  it  will  be  found  that  two-thirds  of 
the  line  rests  upon  the  medullary  portion, 
or  the  pyramid,  and  one-third  upon  the 
cortex;  this  relative  proportion  between 
the  two  parts  is  not  absolute,  but  the 
variations  are  so  slight  that  the  rule  is 
generally  applicable,  and,  by  applying  this 
method  of  measurement,  one  can  usually 
determine,  at  least  approximately,  whether 
the  cortex  is  normal  in  thickness. 

Malformations  and  Malpositions  of  the 
Klidney.' — It  is  necessary  to  consider  these 
conditions  together,  as  malformed  kidneys 
are  not,  as  a  rule,  in  their  normal  positions. 

Abnormalities  in  form  or  position  of  the  kidney  are  not  infrequent.  The 
commonest  of  all  malpositions  is  that  known  as  movable  kidney,  which  is 
'Cragin,  "Amer.  Jour,  of  Obst.."  July.  189S.  Blumer,  "Albany  Med.  An- 
nals." Jan..  1901.  PrcindLsberger,  "Wien.  klin.  Rundschau,"  March  31.  iqoi. 
Guiteras,  '  Monatsberichte  d.  Urologie,"  Bd.  ix,  H.  7,  p.  445-  Hohmeier.  "Zeit. 
f.  Geb.  u.  Gyn.,"  vol.  51.  No.  3.  Rorie,  "Brit.  Med.  Jour.."  April  27.  iqoi.  Gould. 
"Amer.  Jour,  of  Med.  Sci.,"  March,  1Q03.  Morris,  "Surgical  Diseases  of  the 
Kidnev  and  Ureter,"  iqoi.  Horton,  "Northwest  Medicine,"  April.  1903,  p.  198. 
Cathel'in,  "Annal.  des  Mai.  Genito-Urin.,"  vol.  xxi.  No.  23.  Moore,  "Jour,  of 
Anat.  and  Phys.,"  London.  IQ03,  vol.  xxxviii,  p.  09  Hamann.  "Jour,  of  Med. 
Research,"  June,  1902,  vol.  viii.  p.  125.  Obemdorfer,  "Miinch.  mcd.  Woch.." 
March    10.    1003,  p.  426.      Ent^'stron.   "Zeit.  f.  klin.   Med.."    1003.  vol.   49-     Tail- 


Fio.  311. — DiACK  \«  "K  ii  1.1  ion  Supply  to 
Kidney. — (Rindfleifch.) 

b.  .Xrtery  at  the  corticomcdulJary  line,  the 
same  as  s  'n  figure  310.  c,  c.  Blootl- 
vessels  jxi.ssinK  upward  to  SlalpiKhian 
tufts  in  the  cnrtex.  d.  Blood -vesiiels 
fKissing  downward  into  medulla.  The 
diagram  also  shows  the  pyramiils  of 
the  ciirte.x,  between  which  .ire  the 
lab>Tinths  cnnlaininjj  the  Malpighian 
tufts  and  convoluted  tubules. 


630 


SPECIAL  PATHOLOGY. 


generally  an  acquired  condition,  although  authorities  are  agreed  that  the 
organ  may  be  more  movable  than  normal  even  at  birth.  Morris's  statis- 
tics show  that  horseshoe  kidney  occurs  about  once  in  1000  cases ;  absence, 
extreme  atrophy,  or  dwarfing  of  one  kidney,  once  in  2650  cases  The 
typic  sohtary  organ  resulting  from  fusion  of  two  kidneys  is  found  once 
in  16,000  postmortems.  A  single  kidney  is  more  frequent.  According 
to  Winter,^  seven  such  organs  have  been  removed  by  surgeons.  Anoma- 
^  lies  in  the  blood  supply  of  the  kid- 

ney are  not  uncommon;  I  have  re- 
peatedly observed  two  renal  arteries, 
and  three  are  not  infrequent. 


B  B 

Fig.  313. — Horseshoe  Kidney.  (Anterior  aspect.) 
A,  A.  Renal  arteries.  B,  B.  Ureters.  In  this  particular 
case  the  two  ureters  pass  downward  to  the  bladder  and 
enter  separately.  The  end  of  the  organ  to  the  right 
shows  considerable  lobulation,  such  as  is  normal  in 
fetal  life,  but  usually  absent  in  the  fuUy  formed  kidney 
of  the  adult. 


Fig.  312. — Solitary  Kidney.      (Anterior  view.) 
A .  Aorta.     The  small  branch  between  A  and  the 

bifurcation    of    the    aorta    is    the     inferior 

mesenteric  artery  (?).    B,  B.  Common  iliacs. 

It  win  be  observed  that  the  two  renal  arteries 

appear  to  come  off  directly  at  the  bifurcation 

of  the  aorta.     C.  Kidney.     Just    above  the 

letter  C  is  the  ureter.     Posteriorly,  the  organ 

is  shghtly  lobulated.     Absence  of  renal  tissue 

between  the  two  renal  arteries  would  convert 

this  mass  into  a  horseshoe  kidney. — {Drawing 

jrom  specimen  in  the  Museum  oj  the  Jefferson 

Medical  College.) 

The  solitary  kidney  represents  a  fusion  of  the  two  organs  and  their 
development  as  a  single  mass.     As  a  rule,  the  solitary  kidney  possesses 

hefer,  "Soc.  de  Chir.,"  Oct.  28,  1903.  Decherd,  "Amer.  Jour,  of  Med.  Sci.," 
Jan.,  1904.  Cotton,  "Arch,  of  Pediatrics,"  April,  1904.  Dick,  "Trans,  of  Chicago 
Path.  Soc,"  May  9,  1904.  Wood-Jones,  "Brit.  Med.  Jour.,"  Dec.  17,  1904. 
Pohlman,  "Amer.  Med.,"  1904,  vol.  vii,  No.  25,  p.  987;  also  "Bull.  Johns  Hopkins 
Hosp.,"  Feb.,  1905,  p.  49. 

'  "Arch.  f.  klin.  Chir.,"  1903,  Ixix,  No.  3. 


DISEASHS    (U-     1111,     I    KINAKV    i)K(..\NS. 


631 


a  duplicated  blood  supply;  it  liesin  the  median  line  or  slightly  to  one 
side,  and  is  vcrv  much  nearer  the  ])elvis  than  the  normally  placed 
organs;  indeed,  it  may  be  on  the  border  of  or  even  within  the  pelvic 
cavitv.  Commonly,  there  is  but  one  ureter,  although  there  may  be 
two  ureters  or  a  single  ureter  dividing  into  two  before  it  reaches  the 
bladder,  or  two  ureters  uniting  to  form  one  just  before  the  bladder  is 
reached.  The  organ  is  likely  to  be  floating,  although  it  may  be  hrmly 
attached.  Ring  or  "disk-shaped"  kidney  is  a  malformation  intermedi- 
ate between  the  solitary  and  horseshoe  forms. 

Horseshoe  Kidney. — Next  to  the  solitary  kidney,  in  degree  of  mal- 
formation, IS  the  horseshoe  kidney.     In  this  condition  the  two  kidneys 


Fig.  314. — Persistent  Fetal  Kidney  Due  to  Anastcimoses  between  the  Renal  .Arteky  anh  Vein. 

(Natural  size.) 

A.  Renal  artery.     B.  Renal  vein.     C  Ureter.     The  persistence  of  fetal  lobulation  is  well  shown.      It  is  occiision- 

ally  just  as  marked  in  organs  of  a  normal  size. 


may  be  one  continuous  mass,  or  they  may  be  considerably  separated 
with  a  fibrous  band  uniting  them.  The  horseshoe  kidney  lies  with  its 
convexity  downward,  and  usually  possesses  two  pelves  and  two  ureters; 
very  rarely,  such  organs  are  placed  to  one  side  of  the  median  line.  The 
renal  blood-vessels  are  usually  abnormal,  in  that  they  arise  from  or 
join  the  larger  blood-vessels  lower  than  in  health. 

A  single  kidney  is  one  essentially  normal  organ  possessing  the  usual 
blood  su])ply.  It  is  alone  because  of  develo]  mental  arrest  and  conse- 
quent absence  of  the  oj)posite  organ,  and  difTers  from  the  solitary  kidney 
in  that  it  does  not,  histologically  or  anatomically,  although  it  may 
physiologically,  represent  the  two  organs.     It  is  usually  in  the  normal 


632  SPECIAL  PATHOLOGY. 

position,  but,  having  enlarged,  its  increased  weight  sometimes  leads  to 
loss  of  anchorage,  and,  consequently,  to  some  form  of  acquired  mal- 
position. 

Absence  of  the  Kidney. — Rarely,  both  kidneys  may  be  absent; 
absence  or  marked  hypoplasia  of  one  kidney  is  not  so  uncommon. 
Usually,  it  is  the  left'  kidney  that  is  missing;  the  remaining  organ 
hypertrophies  and  performs  the  function  of  two  kidneys.  The  kidneys 
are  not  uncommonly  lobulated,  retaining  this  characteristic  of  fetal 
life.  In  exceptionar  cases  a  third  kidney  is  present.  The  organ  may 
be  near  one  of  the  normally  placed  kidneys,  but  more  commonly  is 
situated  lower  in  the  abdominal  cavity  and  possesses  its  own  ureter 
and  blood  supply.  The  division  of  one  kidney  into  two  or  more  parts, 
receiving  their  blood  supply  from  the  same  vessel  and  draining  into 
the  same  ureter,  does  not  really  constitute  an  example  of  accessory 
or  multiple  organs. 

Nephroptosis,^  ren  mobilis,  or  prolapse  of  the  kidney,  may  be  a  part 
of  a  malformation,  as  already  stated  when  considering  solitary  and 
horseshoe  kidneys.  In  other  cases  it  is  distinctly  an  acquired  mal- 
position. Over  eighty  per  cent,  of  the  misplaced  kidneys  are  found  in 
women,  in  whom  the"^  condition  is  common.  The  frequency  estimated 
by  different  writers  varies:  Kiister  states  that  4.44  per  cent,  of  all 
women  consulting  him  have  movable  kidneys;  Goelet  and  also  Edebohls 
find  that  20  per  cent,  of  women  are  affected;  Harris  states  that  56 
per  cent,  possess  movable  kidneys.  The  morbid  condition  is  most  fre- 
quent during  adult  life, — between  twenty  and  forty, — but  is  also  seen  in 
children  and  infants.  The  right  kidney  is  the  organ  involved  in  over 
eighty  per  cent,  of  the  cases,  and  in  practically  all  the  rest  both  are 
movable.  The  displacement  commonly  follows  pregnancy  or  other 
conditions  that  tend  to  bring  about  an  abnormal  flaccidity  of  the  ab- 
dominal walls.  It  is  frequently  associated  with  morbid  processes  that 
increase  the  size  and  weight  of  the  kidney.  Nephroptosis  may  be 
coincident  with  enteroptosis  or  prolapse  of  other  viscera.  It  is  said 
to  be  favored  by  absorption  of  the  perirenal  fat  and  abnormal  length 
of  the  renal  vessels.  Trauma,  in  the  form  of  blows  and  falls,  may 
displace  the  organ.  Tight  lacing  is  assumed  to  be  a  cause.  Pressure 
upon  the  liver,  induced  by  stays,  is  transmitted  to  the  kidney,  which 
is  thereby  forced  from  its  normal  position. 

The  degree  and,  to  a  certain  extent,  the  character  of  the  mobihty 
vary  in  different  cases.  The  organ  may  be  mobile  behind  the  peri- 
toneum, constituting  the  so-called  movable  kidney;  Morris  and  others 
are  inclined  to  recognize  different  degrees  of  movable  kidney  based  upon 
the  extent  of  the  mobility.  Morris  also  recognizes  a  condition  in  which 
the  retroperitoneal  organ-  may  be  displaced  either  vertically  or  laterally 
in  a  "cinder-sifting  manner."  but  is  not  prolapsed  forward.  In  other 
cases  the  kidney  falls  forward,  bringing  with  it  the  peritoneum,  thereby 

*  Morris,  "Lancet,"  Nov.  30,  1901.  Hutchinson,  "Practitioner,"  Feb.,  1902. 
McWilliams,  "Med.  News,"  Oct.  4,  1902,  p.  625.  Cabot,  "Boston  Med.  and  Surg. 
Jour.,"  March  6,  1902.  Dupoux,  "These  de  Paris,"  1902.  Phillips,  "Lancet," 
March  14,  1903,  p.  731.  Bonney,  "Edinburgh  Med.  Jour.,"  Dec,  1902.  Aaron, 
"Amer.  Med.,"  Dec.  5,  1903,  p.  893.  Harris,  "Jour.  Amer.  Med.  Assoc,"  June  i, 
1901,  also  Feb.  13,  1904,  p.  411.  Treves,  "Practitioner,"  Jan.,  1905,  p.  i.  Mac- 
alister,  "Allbutt's  System  of  Medicine,"  vol.  iv,  p.  350,  gives  references  to  150 
articles  published  prior  to   1897. 


DISEASES  OF  THE   L'KINAkV   ORGANS.  () ^ 

forming  a  pedicle  com])osed  of  the  blood-vessels,  ureters,  nerves,  and 
peritoneum,  constituting^'  what  is  known  as  a  nicsoticphroi.  In  this 
condition  the  ori,'an  is  movable  within  the  abdominal  cavity,  and  is 
called  a  floating  kidney.  Both  the  movable  and  Moating  organs  not 
infrequently  twist  or  kink  the  ureter,  giving  rise  to  obstruction  and 
favoring  the  development  of  hydronephrosis.  Many  of  the  symptoms 
of  floating  kidney  are  due  to  ureteral  obstruction ;  this  feature  also 
explains  the  occurrence  of  the  so-called  urinary  crises,  in  which 
unusual  amounts  of  urine  are  voided  during  exceedingly  brief  periods. 
Thev  result  from  obstruction  and  accumulation  of  urine  in  the  renal 
pelvis,  the  contents  of  which  are  rapidly  discharged  as  soon  as  the 
kidney  resumes  its  normal  position.  Less  commonly,  torsion  gives 
rise  to  a  temporary  obstruction  of  the  blood  supply,  and,  if  the  obstruc- 
tion persist,  gangrene  of  the  organ  sometimes  occurs.  The  kidney  may 
be  displaced  and  caught  by  the  adhesions,  or  in  other  ways  incarcerated. 
The  ectopic  right  kidney  may  drag  upon  the  peritoneum  and  cause 
pressure  on  the  bile-ducts  or  duodenum,  thereby  inducing  gastric  and 
biliary  disturbances;  jaundice  sometimes  occurs.  Coincident  mucous 
coHtis  and  appendicitis  have  been  observed.  Allglave'  discusses  in 
detail  the  possible  altered  relations  of  the  colon  produced  by  movable 
kidney.  Cabot  reports  a  case  of  hematuria  due  to  movable  kidney, 
and  Sutherland-  found  the  ren  mobilis  in  37.5  per  cent,  of  40  cases 
of  orthostatic  albuminuria. 

Malformations  of  the  Ureter. — Sometimes  the  ureter  is  imperforate, 
or,  the  reverse,  sacculated;  occasionally,  one  kidney  may  possess  several 
ureters;  I  have  seen  three  ureters  on  one  side.  Hohmeier  records  an 
instance  where  a  third  ureter  opened  into  the  vagina.  Robinson^  has 
shown  that  the  normal  shape  of  the  ureteral  lumen  varies,  and  often 
the  pair  are  unlike. 

Malformations  of  the  Bladder/  Urethra,  etc.^Occasionally,  the  blad- 
der IS  birid;  sometimes  there  is  a  fissure  of  the  abdominal  and  vesical 
walls,  giving  rise  to  exstrophy,  fissura,  or  inversio  vesicae  ;  rarely,  the 
bladder  is  fissured  in  its  posterior  wall,  and  thereby  communicates  with 
the  pelvic  cavity  or  with  the  vagina  or  rectum.  The  urethra  is  sometimes 
imperforate,  or  the  bladder  and  bowel  may  possess  a  single  opening; 
the  bladder  may  be  absent.  In  a  few  instances  the  bladder  has  been 
found  normally  formed,  but  has  protruded  through  a  fissure  in  the 
abdominal  wall — a  condition  known  as  ectopia  vcsicer.  Persistence  of 
the  urachus  may  be  manifested  by  a  conic  projection  uy)ward  in  the 
median  line,  the  bladder  reaching  almost,  if  not  quite,  to  the  umbilicus. 
In  other  instances  the  atrophic  allantois  may  remain  as  a  tube-like 
extension  above  the  bladder,  ending  at  the  umbilicus,  or  it  may  be 
closed  at  both  ends.  Later,  accumulation  of  fluid  in  the  tube  leads 
to  the  formation  of  a  cyst,  constituting  what  is  known  as  a  cyst  of 
the  urachus.  The  urethra  may  open  on  the  dorsal  aspect  or  on  the 
inferior  surface  of  the  penis,  giving  rise  to  epispadias  and  to  hypospadias, 
respectively.  Hypospadias  may  be  balanic.  penile,  scrotal,  or  jierineo- 
scrotal;     it  occurs  about  once  in  375  male  infants.     Occasionally  the 

'  "Revue  de  Chir.."  Dec.  10.  1004.  p.  730. 

'  "Amer.  Jour,  of  Med.  Sci,"  Aug..  1903. 

'  "Med.  News."  Aur.  8.  1003.  p.  247. 

•Enderlen,  "  Ueber  Blasenektopie."  Wiesbadon.  1004. 


634  SPECIAL  PATHOLOGY. 

urethra  may  possess  more  than  one  external  orifice;  sometimes  the 
meatus  is  bifid.  Occasionally,  the  urethra  has  more  than  one  external 
orifice;  in  rare  instances  the  urethra  opens  behind  the  scrotum,  giving 
rise  to  hypospadias  perineoscrotalis. 

Diseases  of  the  Kidney-bed.^ — Atrophy  of  the  perirenal  jat  has 
been  described  and  it  has  been  suggested  that  abnormal  mobility  of 
the  kidney  may  depend  upon  this  cause.  Inflammation  around  the 
kidney — perinephritis — may  be  acute  or  chronic,  productive  or  sup- 
purative. The  acute  form  is  practically  always  attended  by  the  develop- 
ment of  pus  and  the  formation  of  a  perinephric  abscess.  Usually  it 
is  secondary  to  suppurative  processes  within  the  kidney,  but  may 
result  from  extension  from  contiguous  tissues  or  infection  brought  by 
the  blood.  Primary  perirenal  abscess  is  often  due  to  injury.  Some- 
times the  acute  form  is  protracted  and  there  is  notable  increase  in  the 
fibrous  tissue  forming  the  wall,  with  marked  sclerosis  of  the  contiguous 
fat;  this  has  been  called  chronic  perinephric  abscess.  A  similar  condi- 
tion sometimes  develops  insidiously,  and  is  not  infrequently  manifested 
by  the  occurrence  of  multiple  foci  of  suppuration  embedded  in  a  dense 
fibrous  connective  tissue,  generated  by  inflammatory  hyperplasia  of 
the  contiguous  fibrous  elements.  This  form  is  usually  due  to  chronic 
suppurations  within  the  kidney,  and  especially  to  that  form  of  pyelitis 
which  accompanies  calculi.  Sclerosing  perinephritis  gives  rise  to  a  more 
or  less  marked  increase  in  the  fibrous  tissue  around  the  kidney.  The 
condition  may  be  due  to  inflammations  within  the  kidney  or  it  ma}' 
be  consecutive  to  other  contiguous  irritation.  Sometimes  the  fat  around 
an  incarcerated  movable  kidney  manifests  the  change.  The  kidney  is 
abnormally  firmly  attached,  and  during  removal  brings  with  it  a  large 
amount  of  the  adjacent  tissue. 

Pararenal  cysts  sometimes  occur;  when  composed  of  blood,  they 
are  called  paranephric  hematomata ;  if  the  cysts  contain  urine,  the 
condition  is  called  paranephrosis  or  a  paranephric  urinary  cyst.  Both 
forms  of  extravasation  are  usually  due  to  injury  which  wounds  a  vessel 
or  ruptures  the  pelvis  of  the  kidney  or  the  ureter;  lacerations  of  the 
kidney  substance  may  also  give  rise  to  hemorrhage.  In  the  urosan- 
guineous  cysts  both  urine  and  blood  are  present.  Urine  or  blood  in 
the  paranephric  tissues  favors  the  occurrence  of  infection  and  conse- 
quent suppuration,  and  may  terminate  in  perinephric  abscess. 

Diseases  of  the  Kidney. — For  pathologic  study  of  the  urinary  organs 
it  is  advantageous  to  assume  that  only  a  part  of  these  structures  has 
anything  to  do  with  the  secretion  of  urine.  The  secreting  structure  is, 
of  course,  the  kidney,  and  particularly  that  part  of  the  organ  lying 
superficially,  and  known  as  the  cortex.  A  study  of  the  relation  of 
diseases  of  the  kidney  to  the  different  parts  of  the  organ  will  show  that 
a  number  of  conditions  begin  in,  and  are  largely  restricted  to,  the  essen- 

'  Saritcheff,  "Med.  Obosrenie,"  vol.  Ivii,  No.  3.  Verstraete,  "Jour,  des 
Sciences  med.  de  Lille,"  June  i,  S,  and  15,  1901.  Edlefesen,  "Miinch.  med. 
Woch.,"  Feb.  4,  1902.  Waldvogel,  "Deut.  Zeit.  f.  Chir.,"  June,  1902.  New- 
man, "Brit.  Med.  Jour.,"  July  19,  1902,  p.  167.  Schmidt,  "Miinch.  med.  Woch.," 
April  28,  1903,  p.  731.  Kelley,  "Jour.  Amer.  Med.  Assoc,"  June  27,  1903,  p. 
1775.  Delbet,  "Rev.  de  Chir.,"  July,  1903,  p.  62.  Galladauet,  "Annals  of  Sur- 
gery," April,  1904,  p.  573.  Watson,  "Boston  Med.  and  Surg.  Jour.,"  vol.  cxlix, 
No.  2,  p.  29,  and  No.  3.  p.  64.  Townsend,  "Jour.  Amer.  Med.  Assoc,"  Nov.  26, 
1904,  p.  1626. 


DISEASES  OF   THE  URIXARY   ORCANS.  635 

tial  secreting  tissue.  To  this  group  belong  the  various  forms  of  Bright's 
disease  and  the  acute  degenerative  processes,  and  constitute  what  are 
often  called  the  uudical  Jiscascs  of  the  kidney.  In  another  class  of  cases 
the  lesions  originate  in  the  pelvis,  ureter,  or  bladcJer,  and  extend  by 
continuity  along  the  course  of  the  passage,  eventually  involving,  in 
many  cases,  the  secreting  structure  of  the  kidney.  With  this  group 
of  diseases  are  included  certain  retention  cysts  of  the  kidney  (hydro- 
nephrosis, pyonephrosis),  suppurative  lesions,  and  secondary  suppu- 
rative processes  in  the  urethra,  prostate,  bladder,  ureter,  and  pelvis. 
By  common  consent  these  affections  are  grouped  under  the  temi  surgical 
diseases  of  the  urinary  apparatus.  It  will  be  observed  that  this  division 
into  the  medical  and  surgical  diseases  is  largely  clinical,  but  has  some 
foundation  in  that  the  morbid  conditions  which  eventually  manifest 
themselves  are,  to  a  certain  extent  at  least,  largely  restricted  to  the 
structures  just  indicated. 

Atrophy  of  the  Kidney. — Aside  from  the  arrest  in  development 
already  referred  to  when  considering  malformation  (and  hypoplasia 
is  really  not  an  atrophy),  but  little  is  known  of  atrophic  processes  in 
the  kidney.  The  small  or  contracted  kidney  resulting  from  chronic 
interstitial  inflammation  is  sometimes  referred  to  as  an  atrophied  organ. 

Hypertrophy  of  the  kidney  occurs  to  a  limited  extent  in  both  organs 
in  individuals  addicted  to  drinking  large  quantities  of  fluid,  and  in 
whom  the  kidneys  are  thereby  called  upon  for  unusual  activity.  As  a 
result  of  disease,  of  failure  of  development,  or  of  removal  of  one  organ, 
its  fellow  commonly  manifests  more  or  less  hypertrophy.  The  earlier 
in  life  the  functional  loss  of  one  organ  occurs,  the  more  prompt,  and, 
as  a  rule,  the  more  complete,  will  be  the  compensatory  hypertrophy 
of  the  remaining  kidney.  The  power,  however,  of  continued  enlarge- 
ment persists  until  late  in  life.  During  the  fetal  period  destruction  of 
one  organ  leads  to  enlargement  of  the  remaining  kidney  until  it  ap- 
proximates in  volume  two  fully  developed  organs.  At  this  time  new 
tubules  and  new  Malpighian  tufts  may  be  formed,  but  later  in  life, 
after  the  kidney  has  attained  its  normal  dimensions,  it  is  probable 
that  increase  in  volume  is  the  result  of  a  proportional  increase  in  the 
size  of  the  tubules,  and  is  unassociated  with  the  formation  of  new 
tubules   or  additional  tufts. 

Infiltrations  of  the  Kidney. — Fatty  and  calcareous  infiltrations  are 
rare  in  the  nr)rmal  organ.  Calcification  is  not  infrequent  in  areas  of 
past  necrosis,  such  as  those  resulting  from  tuberculosis,  infarction,  etc. 
Occasionally,  the  kidney  shows  pigmentation  resulting  from  a  deposit 
of  more  or  less  altered  hemoglobin.  The  color  of  the  affected  area  or 
of  the  whole  organ  is  brown,  brownish-yellow,  or  mottled.  Pigments 
so  deposited  may  be  rich  in  iron,  as  can  be  readily  shown  by  the  appli- 
cation of  the  usual  tests.  (See  p.  236.)  In  jaundice  more  or  less  stain- 
ing of  the  kidney  tissue  is  always  evident,  and  usually  necrotic  and 
desquamative  changes  give  rise  to  casts  that  arc  intensely  bile  stained. 
Aside  from  the  concretions  or  true  calculi  occurring  in  the  conducting 
portion  of  the  urinary  tract. — the  pelvis,  ureter,  bladder,  and  urethra, — 
there  is  occasionally  observed,  in  the  kidney  structure  proper,  within 
the  tubules,  and  massed  with  more  or  less  necrotic  e|)ithelium,  deposits 
of  uric  acid  and  urates.  The  so-called  uratic  infarcts,  which  develop 
during  the  first  two  weeks  of  postnatal  life,  are  also  examples  of  depo- 


636 


SPECIAL  PATHOLOGY 


sition  similar  to  that  just  described  and  occurring  in  the  tubules  of 
the  pyramids.  In  diabetes  a  varying  amount  of  glycogenic  infiltration 
may  be  present  in  the  renal  epithelium,  and,  to  a  hmited  extent,  in 
the  Malpighian  bodies.  Lardaceous  disease  of  the  kidney  will  be  con- 
sidered with  the  renal  in- 
flammations. 

Degenerations  of  the 
Kidney,^ — True  fatty  de- 
generation of  the  organ 
can  probably  be  best  con- 
sidered with  chronic  paren- 
chymatous nephritis,  with 
which  it  is  so  constantly 
associated.  A  similar  con- 
version of  the  renal  epith- 
elium into  fat  occurs  in 
pernicious  anemia.  Paren- 
chymatous degeneration 
(cloudy  swelling)  is  prob- 
ably the  most  constant 
morbid  condition  to  be 
recognized  in  the  kidney. 
It  may  result  from  hyper- 
emia, from  congestion,  or 
from  the  presence  of  var- 
ious irritants,  particularly 
those  elaborated  during  the 
progress  of  infectious  dis- 
eases, such  as  scarlet 
fever,  diphtheria,  pneu- 
monia, erysipelas,  etc.  (See  causes  of  acute  Bright's  disease,  p.  641.) 
Anatomically,  the  appearance  of  the  organ  is  largely  dependent  upon 

the  amount  of  vascular  distention  with  which  the  lesion  is  associated. 

In  the   absence   of    hyperemia  or  congestion,  the 

kidney  is    pale,  soft,   and    not    infrequently   pits, 

as  though  it  were  edematous.       The    swelling  is 

often  inconspicuous,  but    can    usually   be    shown 

to  be  present  by  the  fact  that,  upon  incision,  the 

capsule  retracts.      In   the    absence    of    congestion 

or  hyperemia  the  pale,  cloudy   surface    contrasts 

strongly    with    the    bright    luster    of    the    normal 

kidnev.     The  histologic  changes  are  those  already 

described  when  considering  cloudy  swelling.     (See         '.<^ 

p.  241.) 

Hyperemia  of    the  kidney   is   induced   by   ex-      fig. 

posure  to    cold,  by  the  administration  of  irritant 

substances  normally  excreted  through  the  kidney, 

and  it  also  occurs  in  some,  but  not  in  all,  febrile 

conditions,  and  is  present  in  the  initial  stage  of  acute  nephritis.     (See 

causes  of  acute  Bright's  disease.) 

1  Landsteiner,   "Wien.  klin.  Woch.,"  Oct.   10,   1901.      "11  Policlinico,"  Nov 
1902.     Natason,  "Wien.  klin.  Woch.,"  July  16,   1903,  p.  S57.      Landstemer  and 
Mucha,  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.,"  Sept.  30,   1904,  p.  752. 


Fig.  315. — Kidney,  SHOwnxo  Granular  and  Fatty  Degen- 
erations OF  THE  Cortex,  from  a  C.^se  of  PERNiaous 
Anemia. 

Osmic  add  preparation.  Parts  of  three  convoluted  tubes  and 
one  collecting  tube  are  show-n.  The  epitheliurn  of  the  two 
collecting  tubes  near  the  center  of  the  drawing  is  the  seat  of 
advanced  granular  and  fatty  change.  The  protoplasm  is 
granular  and  fragmenting,  and  contains  droplets  of  fat  that 
have  been  blackened  by  the  osmic  acid. 


316 . — Cloudy  Swell- 
ing OF  the  Epithelium 
Lining  a  Kidney  Tu- 
B ITLE . — (Flutter  er. ) 


DI.SIvASKS   OK   Till-:    IKlNAkV    (i  l.:C,  A  \  S  .  637 

Morbid  Anatomy. — The  organ  is  somewhat  hirger  than  normal,  soft, 
and,  on  section,  drijis  blood.  The  cortex  is  very  mucli  darker  than 
that  of  the  normal  organ,  and  is  striated,  while  the  medullary  portion 
may  be  almost  })urj)lish.  Microscopic  examination  usually  shows  dis- 
tention of  the  entire  vascular  area,  and,  at  i)oints,  rhexis;  cloudy  swell- 
ing is  extremely  likely  to  accom])any  the  condition. 

Congestion  of  the  kidney  arises  as  the  result  of  impeded  venous 
circulation,  such  as  may  occur  in  chronic  heart  or  lung  diseases,  or, 
locally,  from  pressure  on  the  renal  veins  by  abdominal  tumors,  ascites, 
and  a  very  much  enlarged  pregnant  uterus.  The  mt^st  advanced  form 
of  congested  kidney  is  the  so-called  cyanotic  kidney  of  chronic  heart 
disease.     (Seep.  518.) 

Morbid  Anatomy. — The  organ  is  usually  large  and  swollen,  and  may 
drip  blood  on  section.  The  tissue  is  firmer  than  normal,  and  resists 
cutting  and  tearing,  owing  to  the  increase  in  connective  tissue.  Unlike 
typic  interstitial  nephritis,  the  capsule  usually  strips  more  easily 
than  normal;  the  cortex  is  of  a  deep-red  color  and  often  striated,  and 
the  pyramids  are  purplish.  Microscopically,  the  epithelium  is  cloudy 
or  granular,  and  at  points  almost  fatty;  there  is  some  increase  in 
interstitial  supporting  structure,  manifested  by  a  small  lymphoid  cell 
accumulation  between  the  tubes,  and  also  an  increase  in  the  fibrous 
tissue — an  evidence  of  past  exudation.  The  amount  of  fibrous  tissue 
may  be  suflScient  to  lead  to  a  slight  reduction  in  the  size  of  the  organ: 
when  the  kidney  is  perceptibly  smaller  than  normal,  it  is  reasonable 
to  assume  that  an  associated  chronic  interstitial  inflammation  is  present. 
The  blood-vessels  are  intensely  engorged,  but  rhexis  is  less  commonly 
present  than  in  the  condition  of  acute  hyperemia. 

Renal  infarction'  results  from  embolic  or  thrombotic  occlusion  of 
the  renal  artery  or  its  branches.  The  infarcts  may  be  multiple  or 
single  and  often  are  of  different  ages;  they  are  usually  anemic.  The 
base  presenting  on  the  surface  of  the  organ  is  round,  oval  or  slightly 
irregular,  pale  or  nearly  white,  and  often  marginated  by  a  hyperemic 
zone  I  mm.  to  2  mm.  in  breadth.  On  account  of  the  capsular  tension 
they  are  rarely  elevated  to  any  perceptible  degree;  the  capsule  is  usually 
loosely  attached  to  the  base  of  the  infarct.  Infarcts  in  the  medulla 
( Fig.  317)  are  less  frequent.  The  affected  kidney  is  commonly  swollen  and 
often  pits  on  pressure.  When  incised ,  the  wedge-shaped  infarct  commonly 
extends  to  the  corticomedullary  junction,  rarely  deej^er.  When  the  in- 
farction is  due  to  fat-embolism,  oil-droplets  are  sometimes  present  in  the 
urine.  Hemorrhagic  infarcts  of  the  kidney  are  much  less  common,  and 
when  present  possess  the  usual  character  of  such  structures.-  In  excep- 
tional cases  the  entire  kidney  is  affected;  in  such  instances  the  process 
is  usually  anemic.  WeigalP  reports  an  instance  of  gangrene  in  a  mov- 
able kidney  due  to  twist  in  the  pedicle. 

Hematuria,  or  blood  in  the  urine,  may  result  from  hemorrhage 
arising  in  the  renal  jiarenchyma  or  from  any  part  of  the  conducting 
[)ath.  Renal  hematuria  may  attend  hyperemia,  congestion,  infarction, 
and  injuries  to  the   kidney  substance,  and  is  p)resent  in  some  forms 

'  Fischler.  "Virchow's  Arch.,"  1902.  Bd.  170,  p.  i.  Schmidt.  "Wien,  klin. 
Woch  .'  May  16,  iqoi. 

'  See  Embolism  and  Infarction,  pp.  278  to  2S4. 
'"Australasian  Med.  Gazette,"  1903,  vol.  xxii,  p.  ^i^. 


638 


SPECIAL  PATHOLOGY. 


of  nephritis,  particularly  the  acute.  It  is  especially  marked  in  the 
so-called  hemorrhagic  nephritis,  but  is  infrequent  in  the  chronic  inflam- 
mations of  the  organ.  It  is  not  certain  whether  or  not  the  hematuria 
accompanying  purpura  and  hemorrhagic  septicemias  is  always  renal; 
the  occasional  presence  of  blood-casts  clearly  indicates  that  the  bleeding 
came  from  the  kidney,  at  least  in  some  cases.  Bleeding  from  the  kidney 
substance  also  occurs  when  primary  or  secondary  tumors  involve  the 
parenchyma  of  the  organ.  Usually  the  hemorrhage  accompanying 
renal  neoplasms  is  the  result  of  involvement  of  the  pelvis  of  the  kidney, 
but  not  always  so,  as  I  have  on  two  occasions  observed  hematuria 
with  blood-casts  and  at  the  autopsy  found  no  structural  lesion  of  the 


Fig. 


317. — Kidney,  Multiple  .\neu3c  Infarcts.     Case  of  Ulcerative  Endocarditis. 


pelvis.  Hematuria  from  a  healthy  kidney,  also  called  renal  hemo- 
philia/ has  been  described.  Hemorrhage  from  the  conducting  portions 
of  the  urinary  organs  may  be  due  to  trauma,  calculi,  ruptured  varicose 
vessels,  certain  diseases  of  the  prostate,  and  tumors.  Among  the  neo- 
plasms, papilloma  and  cancer  are  the  most  frequent  causes.  Parasitic 
hematuria  is  due  to  the  Bilharzia  haematobia,  and  occurs  in  venal  disto- 
matosis^;  hydatid  disease  of  the  kidney  may  be  attended  by  hemorrhage. 

'See  Douglas,  "Surgical  Diseases  of  the  Abdomen,"  1903,  p.  571.  Leube, 
"  Deut.  med.  Woch.,"  1905,  xxxi,  No.  3.  Schenck,  "Med.  News,"  Dec.  24,  1904, 
p.  1206. 

^  See  p.   193. 


DISEASES  OF  THK   URIN'AkY   ORGANS.  639 

When  the  blood  comes  from  the  kidney,  it  is  uniformly  distributed  in 
the  urine,  which  is  rendered  smoky  by  conversion  of  the  hemoglobin 
into  acid-hematin  and  methemoglobin.  Blood  casts  and  other  evidences 
of  renal  involvement  are  usually  present. 

The  term  albuminuria  is  applied  to  that  condition  in  which  serum- 
albumin  or  globulin,  or  both,  occur  in  the  urine.  Two  forms  are  recog- 
nized— phvsiologic  and  pathologic.  In  health,  by  delicate  tests,  a  trace 
of  albumin  may  be  demonstrated  in  the  urine,  particularly  after  exertion 
and  the  ingestion  of  highly  albuminous  food.  The  albuminuria  fol- 
lowing colli  baths,  and  particularly  ocean  loathing,  is  usually  classed 
\\-ith  the  physiologic  type.  The  so-called  physiologic  or  functional 
albuminuria  is  practically  always  of  brief  duration,  or  at  least  inter- 
mittent. Personally  I  am  inclined  to  agree  with  the  insurance  com- 
panies which  decline  to  accept  the  excretion  of  albumin  as  a  normal 
process.  Incidental  albuminuria  results  from  the  addition  of  albumin 
to  the  urine  as  a  result  of  diseases  affecting  the  conducting  passages, 
and  arises  from  essentially  the  same  causes  as  the  analogous  type  of 
hematuria,  which  has  already  been  discussed. 

Pathologic  albuminuria  of  renal  origin  may  be  accepted  as  always 
indicating  some  structural  alteration  in  the  kidney.  It  accompanies 
hyperemia  and  congestion,  is  very  frequently  associated  with  febrile 
processes  and  toxic  conditions,  and  is  almost  constantly  present  in 
inflammation  of  the  kidney.  A  number  of  observers,  and  more  re- 
centlv  Cabot,*  have  shown  that  nephritis  may  occur  without  albuminu- 
ria, and  that  often  the  amount  of  albumin  in  the  urine  bears  no  relation 
to  the  intensity  of  the  renal  inflammation.  With  regard  to  the  exact 
nature  of  albuminuria  we  are  indifferently  informed.  Authorities  are 
not  agreed  as  to  whether  it  is  a  transudate,  an  exudate,  or  a  secretory 
product  of  the  altered  renal  tissue.  The  fact  that  foreign  albumins 
thrown  into  the  blood  quickly  appear  in  the  urine  indicates  that  the 
epithelial  cells  are  able  to  secrete  this  form  of  proteid  matter;  that 
thev  do  so  in  disease  is  not  established.  The  occurrence  of  albuminuria 
in  connection  with  the  heightened  tension  of  renal  congestion  and 
hvperemia  suggests  transudation,  and  the  frequent  abundance  of 
albumin  in  the  urine  from  kidneys  in  which  admittedly  exudative 
inflammations  are  in  progress  may  be  taken  as  establishing  its 
production  bv  exudation.  The  three  illustrations  just  mentioned,  and 
others  that  might  be  given,  clearly  indie  i  that  the  albumin  does  not 
alwavs  result  from  the  same  primitive  chan';e  in  the  kidney. 

Renal  casts-  are  cylindric  bodies  formed  in  the  uriniferous  tubules, 
from  which  they  are  discharged  into  the  urine.  Of  the  manv  sug- 
gested methods  by  which  they  are  produced,  three  are  deserving  of 
mention.  Rovida  believed  they  were  derived  from  epithelial  cells, 
and.  in  a  sense,  were  secretory  products.  Key  and  also  Bayer  con- 
ceded the  epithelial  origin  of  these  bodies,  but  thought  they  resulted 
from  destructive  metamorphosis  of  the  renal  epithelium.  Following 
Traube.  many  have  contended  that  they  are  solidified  exudates  and 

*  "lour,  of  Amer.  Med.  Assoc."  March  18.  1905.  See  also  Koresi.  "Wien. 
klin.  Woch.."  Oct.  13,  1904,  p.  1075.     Orgler.  "Virchow's  Arch.."  1904.  Bd.  176, 

P-  41^- 

'The  literature  of  the  subject  may  be  followed  from  Coplin.   "Phila.   Med. 

Jour."   March  S.    1902. 


640  SPECIAL  PATHOLOGY. 

always  due  to  inflammation.  The  theory  that  they  are  composed  of 
albumin,  solidified  in  the  tubules  by  the  action  of  urine,  is  suggestive 
of  their  exudative  origin.  Microchemically  it  is  possible  to  demon- 
strate that  some  of  the  casts  contain  mucin,  others  give  the  reaction 
for  fibrin,  and  many  contain  fat.  These  facts,  however,  do  not  elucidate 
their  origin;  it  is  probable  that  they  arise  in  more  than  one  of  the 
ways  suggested,  and  that  under  different  conditions  the  process  by 
which  they  are  formed  is  not  always  the  same.  Casts  containing  blood 
are  called  blood  casts.  When  the  epithelial  cells,  adhering  to,  or  forming 
part  of,  the  structure,  can  be  identified,  they  are  known  as  epithelial 
casts.  The  granular  cast  probably  results  from  degeneration  of  epithe- 
lial cells  and  other  structures,  possibly  leukocytes,  attached  to  or  forming 
part  of  the  cast.  In  a  similar  way  fatty  change  gives  rise  to  fatty 
casts.  Large,  rigid,  highly  refractile  cylinders  of  this  type  are  called 
waxy  casts.  Hyaline  casts  are  usually  smaller,  structureless,  and  difficult 
to  recognize.  It  is  not  improbable  that  the  body  or  core  of  other  forms 
of  casts  is  composed  of  a  substance  resembling,  or  identical  with,  that 
found  in  the  hyaline  cast.  Casts  composed  of  leukocytes,  and  others 
containing  numerous  bacteria,  occasionally  are  found  in  the  urine. ^  It 
is  well  known  that  on  standing  casts  may  disappear  from  the  urine, 
and  that  they  are  most  abundant  in  specimens  freshly  voided.  In  the 
presence  of  pus  they  rapidly  disintegrate,  and  the  larger  the  number 
of  bacteria,  the  more  rapid  the  disintegration.  Treutlein-  has  shown 
that  some  bacteria  are  more  active  than  others  in  the  destruction  of 
casts.     He  calls  the  process  cylindrolysis. 

Nephritis  or  inflammation  of  the  kidney  includes  a  number  of  the  most 
important  diseases,  and  at  the  same  time,  because  of  its  varied  manifesta- 
tions, offers  the  greatest  difficulty  in  the  systematic  grouping  of  the  various 
forms.  In  the  present  state  of  our  knowledge  it  is  impossible  to  say  ex- 
actl}^  what  changes  in  the  kidney  are  inflammatory  and  thereby  draw  a 
sharp  line  between  nephritis  and  the  degenerations  and  necroses  that 
affect  the  organ.  Clinically,  it  is  possible  to  recognize  acute  and  chronic 
forms,  and  usually  the  anatomic  changes  enable  us  to  differentiate  the 
organs  resulting  from  recent  active  inflammatory  processes,  from  those  in 
which  the  affection  is  of  longer  duration.  In  some  inflammations  of  the 
kidney  inflammatory  exudates  are  formed  within  the  tubules  or  in  the 
interstitial  structure,  and  to  such  processes  the  name  exudative  nephri- 
tis has  been  applied.  In  other  cases,  often  without  marked  alteration 
in  the  epithelium  of  the  organ,  particularly  in  the  earlier  stages,  there 
is  a  notable  increase  in  the  fibrous  tissue  between  the  tubules,  justifying 
the  term  productive  nephritis.  In  still  another  group  of  cases  exudation 
is  absent  or  but  slight,  and  retrograde  changes  in  the  epithelium  con- 
spicuous; these  have  been  called  degenerative  inflammations.  Occa- 
sionally exudative,  productive,  and  degenerative  lesions  affect  the 
same  organ,  giving  rise  to  an  extremelv  confusing  anatomic  picture 
that  does  not  adapt  itself  to  any  one  of  the  previously  mentioned  groups. 
As  is  well  known,  the  kidney,  like  other  glandular  viscera,  is  composed 
of  a  connective-tissue  framework  in  which  are  distributed  the  blood- 
vessels, lymphatics,  and  nerves;    this  structure  is  called  the  interstitial 

*  For  methods  of  demonstration  and  illustrations  showing  different  forms  of 
casts  see  chapter  on  Examination  of  the  Urine  at  the  end  of  this  volume. 
'"Miinch.  med.  Woch.,"   1903,  No.  35. 


niSHASKS  OF  TIIK   rklNAKY   OKGANS.  64I 

tissue.  The  part  of  the  kichicy  which  accompHshes  secretion  is  the 
epitheUum  Hninjj  the  tubules  and  the  Malpighian  tufts;  this  constitutes 
the  parenchyma  of  the  ori,'an.  The  recognition  of  the  two  types  of 
tissue  led  to  the  classification  of  renal  inflammations  based  upon  this 
fact.  Interstitial  nephritis  was  su])posed  to  have  its  origin,  and  to 
induce  its  ct)nspii,  uous  changes,  in  the  interstitial  tissue.  Parenchy- 
matous nephritis,  on  the  other  hand,  was  presumed  to  arise  in,  and  to 
be  largcl\'  rcstritted  to,  the  epithelium  of  the  tubules,  and  hence  by 
some  writers  it  is  called  catarrhal  nephritis.  It  was  soon  recognized  that, 
neither  clinically  nor  anatomically,  is  it  possible  to  establish  a  form  of 
renal  inflammation  affecting  either  the  interstitial  tissue  or  the  tubular 
tissue  exclusively.  The  recognition  of  this  fact  led  to  a  further  group 
in  which  both  the  interstitial  and  the  parenchymatous  structures  were 
involved,  and  to  which  the  name  diffuse  nephritis  has  been  given. 

All  attempts  to  bring  order  out  of  tliis  chaos  have  been  unpro- 
ductive of  satisfactory  results.  No  classification  of  renal  inflamma- 
tions has  met  the  approval  of  both  clinicians  and  pathologi.sts.  The 
extremelv  complex  groupings,  rendered  possible  by  an  accurate  knowl- 
edge of  the  morbid  anatomy,  do  not  yield  themselves  to  the  clinical 
picture  encountered  in  the  sick.  For  this  reason  I  shall  adopt  a  classi- 
fication of  renal  lesions  into  forms  that  can  be  recognized  clinically, 
and  will  at  the  same  time  point  out  the  anatomic  differences  upon 
which  more  detailed  subdivisions  may  be  made.  I  shall  consider — (i) 
the  acute  suppurative  interstitial  nephritis.  (2)  Acute  Bright's  disease 
or  acute  diffuse  nephritis,  w'ith  which  1  shall  include  the  acute  nonsuppura- 
tive interstitial  nephritis  and  the  acute  parenchymatous  nephritis.  (3) 
Chronic  diffuse  nephritis,  embracing  both  the  large  white  and  the  small 
white  kidney,  is  also  called  chronic  parenchymatous  nephritis.  (4) 
Chronic  interstitial  nephritis.  This  classification^  must  be  regarded 
as  provisional,  adapting  itself  to  the  recognized  clinical  forms  of 
nephritis  and  offering  an  acceptable  basis  for  appropriate  description  of 
the  lesions  observed. 

Acute  suppurative  nephritis  is  an  inflammation  of  the  kidney  at- 
tended bv  the  production  of  an  exudate  in  which  polymorphonuclear 
leukocvtes  predominate.  Primarily  the  process  is  intertubular,  and 
might  with  propriety  be  called  acute  suppurative  interstitial  nephritis. 
In  some  cases  definite  abscess  formation  results,  while  in  others  the 
suppuration  seems  more  diffuse.  Necessarily  the  process  is  due  to 
infection  bv  pyogenic  bacteria.  These  organisms  may  reach  the  kidney 
bv  extension  from  the  pelvis  (pyelonephritis),  by  invasion  from  the 
perinephric  tissues,  and  by  the  blood;  the  last  is  the  usual  path.  The 
bacteria  commonly  ])resent  are  streptococci,  pneumococci,  staphylo- 
cocci, the  Bacillus  coli,  and  the  typhoid  bacillus.  Something  in  the  viru- 
lence of  the  organism,  in  the  susceptibility  of  the  patient,  or  something 
in  the  associated  intoxication,  seems  necessary  to  ])rofluce  definite 
colonization  from  hematogenous  infection.  It  is  well  known  that  in 
typhoid  and  pneumonia  the  specific  organism  is  commonly  present  in 

*  Those  desiring;  to  familiarize  themselves  with  other  classifications  should 
consult  Councilman.  "Med.  and  Surg.  Reports  of  the  Boston  City  Hospital," 
eighth  series.  1897,  p.  31.  Bradford,  "Lancet."  July  4.  1903,  p.  1,  July  16.  1904. 
p.125.  and  luly  23,  1904.  p.  191.  Tyson,  "  Bright  s  Disease  and  DiaVjetes,"  1904, 
pp.  S3  to  99.      Herrick.  "NIed.  Rec,"  June  14.   1902. 


642 


SPECIAL  PATHOLOGY 


the  blood,  and  still  acute  suppurative  nephritis  may  be  regarded  as 
an  infrequent  complication  of  these  conditions,  while  the  nonsuppurative 
form  of  interstitial  nephritis  occurs  much  more  commonly.  It  may 
be  that  congenital  peculiarity  ^  determines  unusual  susceptibility,  but 
probably  the  question  of  intensity  of  infection  and  lessened  resistance 
on  the  part  of  the  tissues  are  the  important  factors.  A  true  suppurative 
nephritis  occasionally  accompanies  diphtheria  and  scarlet  fever,  in  which 
conditions  it  often  appears  to  be  superadded  to  the  acute  parenchy- 
matous or  acute  nonsuppurative  lesion.  In  pyemia  and  septicemia, 
and  in  processes  associated  with  the  presence  of  infected  emboli,  an 
acute  suppurative  nephritis  progressing  to  abscess  formation  is  not 
infrequently  present. 


Fig.  318. — Kidney,  Acute  Suppurative  Interstitial  Nephritis. 
A  and  B.  Distended  blood-vessels;  the  numerous  leukocytes  mi.xed  with  the  erythrocytes  are  almost  e.tclusively 
of  the  polymorphonuclear  type,  and  the  same  ceils  form  the  major  portion  of  the  intertubular  exudate,  although 
a  few  red  cells  have  also  escaped.  The  swelling  is  indicated  by  the  dissociation  of  the  interstitial  tissue.  The 
variation  in  size  manifested  by  the  red  cells  is  the  result  of  sectioning,  many  of  them  having  been  divided  by 
the  knife.  C.  Tubule  which  has  shed  most  of  its  epithelium;  the  remaining  cells  in  this  tubule  and  those 
present  in  other  tubules  are  advancedly  granular,  evidently  necrotic. 

Morbid  Anatomy. — In  the  absence  of  recognizable  abscesses  the 
macroscopic  differentiation  of  this  condition  is  often  most  difhcult 
and  sometimes  impossible.  The  organ  is  usually  enlarged — sometimes 
the  swelling  is  extremely  marked;  the  capsule  is  tense,  and  occasionally 
grayish  miliary  abscesses  may  be  recognized  in  subcapsular  tissues. 
When  incised,  the  capsule  retracts  and  the  cortex  bulges;  the  resistance 
to  incision  is  not  increased.  The  appearance  of  the  cut  surface  is  rarely 
the  same  in  any  two  cases.  In  some  instances  it  is  pale,  in  others 
hyperemic,  and  may  drip  blood,  particularly  if  the  condition  be  asso- 

'  For  suggestive  paper  dealing  with  the  susceptibilities  to  nephritis  see  Cas- 
taigne  and  Rathery,  "La  Sem.  Med.,"   1903,  p.  309. 


DISKASES   OF  THE    LKIN'AKY  'JKGAVS.  643 

ciated  with  an  acute  diffuse  lesion.  Where  the  infection  has  extended 
from  the  pelvis  (pyelonephritis),  the  lines  of  suppuration  may  often 
be  traced  in  the  pyramids  and  extendinjj  upward  into  the  cortex;  they 
consist  of  grayish,  white,  or  whitish-yellow  striae  radiating  from  the 
apex  of  the  pyramid.  When  miliary  abscesses  are  present,  the  incised 
surface  is  dotted  with  yellowish  or  yellowish-white  bodies  i  mm.  to 
2  mm.  in  diameter;  in  some  points  these  may  have  become  confluent, 
producing  abscesses  of  larger  size.  The  embolic  abscesses  may  be  dis- 
tinctly conical  or  confluence  may  give  rise  to  irregular  areas  of  sup- 
puration. In  hematogenous  infection,  unattended  by  macroscopic 
evidences  of  embolism,  suppuration  is  frequently  conspicuous  in  the 
areas  of  the  labyrinth,  some  of  which  may  be  outlined  with  remarkable 
clearness.  In  some  instances  of  infection  from  the  blood  striae  in  the 
pyramids  result  from  interstitial  suppuration  between  the  straight 
tubules,  which  may  also  be  due  to  extension  from  the  tubules,  carrying 
bacteria  derived  from  centers  of  infection  in  the  areas  of  the  labyrinth. 

The  histology  of  the  affection  is  almost  as  varied  as  the  gross  anatomy, 
but  the  affection  is  constantly  differentiated  from  other  forms  of  nephritis 
by  the  enormous  numbers  of  polymorphonuclear  leukocytes  observed  in 
the  lesion.  Other  white  blood-cells  may  be  present,  but,  when  compared 
with  the  predominant  pus-cell,  are  never  numerous.  The  enlargement 
of  the  organ  is  due  to  a  marked  intertubular  swelling  and  cell  accumu- 
lation. Necessarily  the  parenchyma  suffers  in  direct  proportion  to  the 
intensity  of  the  process.  In  the  beginning  of  the  lesion,  or  toward  the 
margin  of  defined  abscesses,  the  tubular  epithelium  is  found  necrotic, 
granular,  and  desquamating;  often  distinct  casts  composed  of  the 
necrotic  cells  are  observed  within  the  tubes;  many  of  the  affected 
tubules  contain  cylinders  in  which  the  number  of  polymorphonuclear 
leukocytes  is  sufficient  to  justify  the  name  pus  casts.  In  the  Mal- 
pighian  tufts  definite  emboli  may  be  recognized,  and  sometimes  hyaline 
thrombi  are  present;  there  is  practically  always  a  cellular  exudate 
into  the  cavity  of  the  tuft,  and  within  this  numerous  polymorpho- 
nuclear leukocytes  are  frequently  found.  Throughout  the  lesions  the 
causative  bacteria  are  present  in  varying  numbers;  in  some  cases 
bacterial  plugs,  or  definite  colonies,  may  be  recognized  in  the  capil- 
laries, especially  of  the  tuft;  in  other  cases  the  number  of  bacteria 
is  small  and  the  organisms  proportionately  difficult  to  find.  It  is  well 
known  that  the  acute  diffuse  and  acute  nonsupi)urative  interstitial  ne- 
phritis may  involve  kidneys  which,  by  all  the  methods  at  our  disposal, 
appear  sterile.  I  do  not  believe  that  acute  suppurative  nephritis  ever  • 
occurs  in  the  absence  of  bacteria  within  the  lesion.  Occasionally  a  large 
amount  of  blood  will  be  found  diffused  through  such  kidneys,  thereby 
constituting  a  form  of  hemorrhagic  neythritis;    such  cases  are  rare. 

Under  the  term  acute   Bright's  disease '  or  acute  diffuse  nephritis 

'See  references  to  Councilman,  and  Bradford,  foot-note  on  p.  641.  Also 
Councilman,  "Trans.  Assoc.  Amer.  Phvs.,"  1S98,  vol.  xiii.  Baginsky,  "Arch.  f. 
Kinderheilk.,"  xx.xiii.  Xos.  i  and  2.  Howard,  "Amer.  Jour,  of  Med.  Sci.."  Feb., 
iQoi.  Raymond  and  Hulot,  "Soc.  de  Biol.,"  Dec.  21.  iqoi.  Miller,  'Arch,  of 
Pediatrics,"  Jan.,  i(jo2.  Welch  and  Schamber^,  '  Phila.  Med.  Jour.,"  Nov.  i, 
1902,  p.  637.  Mensi,  "Gazetta  Medicina  Italiana,"  1903.  21.  p.  207.  Swan. 
"Amer.  Jour,  of  Med.  Sci.."  1904.  Lyon.  "Jour,  of  Path,  and  Bact.."  Julv.  1904, 
p.  400.  Fichera  and  ScatTidi.  "Virchow's  Arch.."  1904.  vol.  177.  p.  63.  flamini, 
"II  Policlin.."  Sept.,  1904.  Sollmann,  "Jour.  Amer.  Med  .V-i*;"!"-  "  \"mv  ^f>  moi. 
p.  22.     Reichel.  "Zeit.  f.  Heilk.,"  1905.  Bd.  xxvi,  H,  i. 


644  SPECIAL  PATHOLOGY. 

I  shall  include  the  renal  inflammations  to  which  the  names  acute  paren- 
chymatous ncpJiritis,  acute  degenerative  nephritis,  acute  tubular  nephritis, 
acute  catarrhal  nephritis,  fibrijwiis  nephritis,  and  acute  desquamative 
nephritis,  have  been  applied.  I  shall  also  place  with  this  group  the 
anatomic  form  which  justifies  the  name  acute  notisuppurative  inter- 
stitial nephritis.  Councilman  is  clearly  correct  in  maintaining  a  distinct 
anatomic  position  for  this  type  of  renal  inflammation,  but  I  am  advised 
by  clinicians  (Tyson  takes  this  view)  that  it  offers  no  symptomatic 
phenomena  by  which  it  can  be  distinguished  from  closely  allied  con- 
ditions. 

Acute  nephritis  is  a  manifestation  of  renal  irritation,  and  the  irri- 
tants that  may  give  rise  to  the  condition  are  many  and  varied.  Of 
the  large  number  of  medicaments  enumerated  by  Sollmann  as  capable 
of  producing  nephritis,  turpentine,  cantharides,  potassium  chlorate, 
carbolic  acid,  less  commonly  cubebs  and  copaiba,  and  certain  metals, 
among  which  should  be  mentioned  arsenic,  mercury,  phosphorus,  and 
the  salts  of  chromium,  are  especially  important.  The  influence  of  cold 
and  exposure  has  been  variously  estimated ;  the  statement  that  ' '  a 
man  gets  drunk,'  sleeps  in  a  ditch,  and  passes  bloody  urine  the  next 
morning"  has  been  very  generally  accepted  as  epitomizing  a  clinical 
observation.  Such  influences  probably  act  by  suppressing  cutaneous 
secretion  and  proportionately  increasing  the  quantity,  and  possibly  alter- 
ing the  character,  of  the  irritants  which  the  kidney  must  excrete.  This 
necessarily  enhances  the  renal  irritation  and,  if  not  actually  productive 
of  inflammation,  must  increase  tissue  susceptibility  to  other  factors 
giving  rise  to  acute  nephritis.  An  acute  inflammation  of  this  type 
sometimes  accompanies  gestation,  in  which  condition  it  is  probably 
a  part  of  the  toxemia  of  pregnane}^  to  which  I  have  referred  on  page 
80.  Clinically  nephritis  of  the  acute  type  is  so  frequently  associated 
with  certain  infectious  diseases,  especially  scarlet  fever  and  diphtheria, 
that  it  is  sometimes  referred  to  as  postdiphtherial  or  postscarlatinal 
nephritis.  Acute  renal  inflammation  is  a  frequent  manifestation  in 
puerperal  and  other  forms  of  sepsis,  which,  with  propriety,  may  be 
considered  with  the  infectious  diseases.  Miller  has  been  able  to  collect 
forty  cases  of  influenzal  nephritis  in  which  the  renal  manifestation 
sometimes  assumes  a  hemorrhagic  type.  Welch  and  Schamberg  found 
albumin  in  sixty-five  per  cent,  of  the  cases  of  smallpox,  and  in  forty-five 
per  cent,  casts  were  also  present.  As  a  rule,  variolous  nephritis  is  less 
intense  than  that  occurring  in  scarlet  fever.  Pneumonia,  both  croupous 
and  bronchial,  more  commonly  the  former,  may  also  give  rise  to  the 
condition.  The  nephritis  accompanying  erysipelas  may  be  of  this  type 
or  it  may  be  acute  suppurative,  and  in  some  cases  both  lesions  are 
concurrent.  Acute  nephritis  may  be  produced  by  the  injection  of 
bacterial  toxins,  especially  the  poisons  derived  from  the  diphtheria 
bacillus,  and  in  the  infectious  diseases,  with  which  it  occurs,  it  seems 
reasonably  evident  that  the  renal  disturbance  is  due  to  the  action  of 
toxic  substances  reaching  the  kidney  by  the  blood.  The  nephritis  occa- 
sionally accompanying  syphilis^  may  be  of  this  type.     It  is  sometimes 

^  See  Hoffman,  "Berl.  klin.  Woch.,"  March  3,  1902.  Waldvogel,  "Deut.  med. 
Woch.,"  Oct.  30,  igo2.  Wagner,  "Miinch  med.  Woch.,"  Dec.  16,  and  Dec.  23, 
1902,  p.  2150.  Miihlig,  "Miinch.  med.  Woch.,"  March  24,  1903,  p.  505.  Car- 
penter, "Lancet,"  Aug.  15,  1903,  p.  473.  Sutherland  and  Walker,  "Brit.  Med. 
Jour.,"  April  25,  1903,  p.  959.  Schlechtendahl,  "Wien.  klin.  Rundschau,"  Aug. 
16,  1903.     Thiemann,  "Mimch.  med.  Woch.,"  Jan.  31,  1905. 


iiim:asi-:s  ok  the  urinary  organs.  ^145 

dillicult  to  say  whether  the  inilammation  is  due  to  the  syphiii^  or  to  the 
mercurv  used  in  treatment;  as  some  cases  lecover  durinj,'  the  continu- 
ous administration  of  the  remedy,  it  is  evident  that  the  latter  is  not 
the  cause  in  all  instances.  It  is  to  be  remembered  that  syphilis  may 
also  induce  chronic  forms  of  nephritis.  The  acute  inHammation  accom- 
panying syphilis  is  frecjuently  hemorrhagic,  and  the  amount  of  albumin 
present  is  sometimes  enormous;  in  the  case  reported  by  Hoffman,  the 
urine  contained  eight  ])er  cent,  (by  weight)  of  albumin. 

The  foregoing  summary  of  the  conditions  under  which  acute  nephritis 
mav  occur  clearly  indicates  that  we  can  not  look  upon  the  disease 
as  etiologicallv  specitic.  It  is  a  result  of  the  action  of  irritants  upon 
the  kidnev.  and  as  these  substances  differ  in  kind,  and  in  intensity  of 
action,  the  varied  morbid  anatomy,  and  somewhat  inconstant  symptoma- 
tology, could,  with  safety,  be  predicted.  Vaughan  proposes  to  call  the 
poisons  producing  necrosis  and  inflammation  of  the  kidney  nephro- 
lysins  ;  unfortunately,  the  term  has  been  used  with  a  slightly  different 
meaning  and  can  not  be  applied  without  danger  or  confusion.  Linde- 
mann,  by  subjecting  guinea-pigs  to  hypodermic  injections  of  emulsions 
prepared  from  the  kidneys  of  rabbits,  obtained,  from  the  treated  ani- 
mals, a  nephrolytic  serum  ^  capable  of  producing  albuminuria  and  renal 
inflammation  when  injected  into  dogs. 

Morbid  Anatowy. — Both  kidneys  are  affected,  but  often  to  different 
degrees.  The  appearances  observed  postmortem  are  modified  by  the 
duration  and  intensity  of  the  process,  the  presence  or  absence  of  com- 
plications, and  also  the  previous  condition  of  the  affected  organ.  In 
the  earlier  stages  the  kidney  may  show  no  conspicuous  alteration,  or 
at  least  nothing  indicative  of  this  form  of  nephritis ;  usually  such 
organs  are  intensely  hyperemic  and  mottled,  but  they  may  be  pale. 
When  the  condition  is  fully  developed,  the  kidney  is  swollen,  often 
conspicuously  enlarged,  the  capsule  tense  and  immediately  retracting 
on  incision.  It  is  less  firmly  attached  than  nonnal  and  strips  off  readily. 
In  the  i)resence  of  marked  edema  the  capsular  adhesion  is  very  much 
less  firm  than  in  normal  kidneys.  The  resistance  to  incision  is  less 
than  in  health  and  the  incised  surface  bulges.  The  evident  increased 
tension  is  often  made  apparent  by  the  bulging  which  follows  a  slight 
cut  through  the  capsule  of  a  previously  unopened  organ,  and  it  is  pos- 
sible that  the  pallor  sometimes  seen  is  partly  due  to  the  blood  being 
expressed  by  the  recoil  of  the  extremely  tense  capsule.  In  the  presence 
of  marked  hyperemia  and  associated  edema,  the  incised  surface  may 
drip  blood  or  bloody  serum.  Closer  inspection  shows  that  the  swelling 
is  most  conspicuous  in  the  cortex,  which  is  usually  greatly  broadened. 
When  the  hyperemia  is  not  intense,  the  areas  of  the  labyrinth  are 
redder  than  the  adjacent  cortical  pyramids  or  the  medulla;  this  gives 
rise  to  cortical  striation,  which  in  some  cases  is  conspicuous.  Punctate 
hemorrhages  are  sometimes  present.  As  the  disease  progresses  the  in- 
tense hyperemia  gradually  lessens  and  the  organ  becomes  paler.  In 
the  later  stages  it  is  often  possible  to  detect  cortical  striation  due  to 
the  necrotic  and  degenerative  changes  in  the  areas  of  the  labyrinth. 
When  such  retrograde  alterations  are  marke<l,  the  areas  containing  the 

•  Schultze.   "Deut.  med.   Woch.."   1900.   No.   ;;.     Ascoli  and  Figari.   "Bed. 

klin.   Woch     "     •""•"    "■      '■■■"'         T'.-,rr-i.     ■lour     .,f'   Mr.l      Ri'S.-:irrJi   ■'    luoi.    vol     xii. 

p.  I. 


646 


SPECIAL   PATHOLOGY. 


convoluted  tubules  are  extremely  pale.  The  decapsulated  and  incised 
surfaces  of  the  organ  are  often  mottled,  due  to  different  degrees  of 
hyperemia,  and  areas  of  necrosis  and  degeneration  irregularly  distributed 
in  the  superficial  cortex  and  within  the  organ.  Often  the  Malpighian 
bodies  can  not  be  recognized;  in  other  cases  they  are  pale  and  bloodless, 
but  when  involved  in  the  inflammatory  process  they  appear  dark  and 
intensely  hyperemic  in  the  earlier  stages  and  later  become  pale  from 
the  presence  of  the  exudate  and  associated  necrosis  and  degeneration. 
The  pelvis  of  the  kidney  is  occasionally  the  seat  of  well-marked  inflam- 
mation; the  mucosa  may  be  red  and'  injected  and  manifest  the  usual 
evidences  of  an  acute  catarrhal  inflammation.  In  rare  cases  a  distinct 
pseudomembrane  is  present.  Hemorrhages  in  the  renal  bed  are  in- 
frequent, and  when  present  are  usually  petechial  or  ecchymotic.  (See 
Plate  IX,  Figs.  2  and  3.) 


Fig.  319. — Kidney,  Acute.  Xonsuppur.^tive,  Interstitial  Nephritis.  (Compare  with  Fig.  318.) 
A  to  B.  Between  the  leaders  from  these  points  the  renal  architecture  has  been  largely  destroyed  and  replaced  by 
leukocytes,  almost  e.xclusivelv  of  the  mononuclear  type.  C.  Small  vessel  containing  fragmented  red  blood- 
cells  and  an  excess  of  leukocytes,  one  of  which,  the  second  above  the  leader,  is  a  typical  polymorphonuclear 
white  cell.  D.  Two  tubules  from  which  the  epithehum  has  been  shed.  E  and  F.  Tubules  m  which  epithe- 
lial desquamation  is  progressing;  the  alteration  is  more  marked  in  F.  The  artist  has  brought  out  the  nuclei 
of  epithelial  cells  with  unmerited  accentuation,  as  in  this  condition  they  rarely  show  so  clearly. 

The  histologic  changes  are  also  varied.  In  some  cases,  and  it  is 
probable  that  this  is  a  beginning  inflammation,  the  interstitial  change 
is  slight— scarcely  perceptible.  The  renal  epithelium  is  granular,  ne- 
crotic, and  desquamating;  granular  casts  can  be  seen  in  the  tubes 
and  sometimes  blood  casts  are  present.  The  epithelium  of  the  Mal- 
pighian tufts  is  also  swollen,  and  there  may  be  some  evidence  of  ex- 
foliation. It  ^vill  be  observed  that  the  brunt  of  the  process  falls  on 
the  secreting  epithelium,  and  hence  justifies  the  name  acute  paren- 
chymatous nephritis.     In   another  group  of  cases  the   changes  in  the 


DISEASES   OF   THE    UKINAKY   OKCANS.  647 

t 

epithelium  are  similar  to  those  already  described,  the  hyperemia  is 
much  more  intense,  and  cellular  exudation  is  present  between  the 
tubules.  In  some  of  these  cases  the  intercellular  changes  are  most 
conspicuous.  The  migrated  cells  are  mostly  mononuclear  leukocytes, 
and.  as  shown  by  Councilman,  Howard,  and  Lyon,  plasma  cells'  are 
often  exceedingly  abundant.  These  latter  structures  frequently  contain 
mitotic  figures.  In  the  absence  of  frank  infection  y)olymc)ri)honuclear 
leukocytes  are  not  numerous.  In  these  cases  the  tubular  change  may 
be  slight;  the  most  conspicuous  alteration  is  exudation  in  the  inter- 
tubular  structures,  and  for  this  reason  the  condition  has  been  called 
acute  nonsuppurative  interstitial  nephritis.  It  must  not  be  gathered, 
howcyer,  that  the  parenchyma  escapes;  the  parenchymatous  changes 
are  always  present  and  sometimes  marked,  and  in  this  sense  the  lesion  is 
an  acute  diffuse  nephritis,  inyolying  both  the  interstitial  and  the  tubular 
tissues.  Casts  are  numerous  within  the  tubules,  and  may  be  granu- 
lar, epithelial,  leukocytic,  or  contain  red  blood-cells.  The  glomerular 
changes  in  the  different  forms  of  diffuse  nephritis  vary.  In  the  acute, 
nonsuppurative  interstitial  nephritis  the  capillaries  of  the  tufts  contain 
but  few  or  no  red  cells.  Hyaline  thrombi  are  sometimes  present  and 
fibrin  may  be  demonstrated  within  and  around  the  tuft  and  sometimes 
in  the  interstitial  tissue.  In  glomerular  nephritis  the  tuft  changes 
are  most  conspicuous.  Mononuclear  cells,  many  of  which  are  the  plasma 
cell  type,  form  mantles  around  the  tuft;  the  epithelium  is  desquamating, 
and  a  hyaline  or  granular  deposit  fills  the  space  between  the  mass  of 
convoluted  capillaries  and  the  capsule  of  Bowman.  The  desquamated 
epithelium  is  granular  and  late  in  the  affection  may  be  shown  to  contain 
fat.  Those  cases  of  nephritis  in  which  epithelial  desquamation  is 
marked,  often  leaving  manv  tubules  stripped  of  their  lining  cells,  have 
been  called  instances  of  acute  desquamating  nephritis  or  acute  catarrhal 
nephritis. 

Bacteria  are  frequently  absent  in  this  form  of  renal  inflammation, 
and  It  has  been  clearly  established  that  they  are  in  no  wav  necessary 
for  Its  production.  Streptococci,  pneumococci.  staphylococci,  the  diph- 
theria bacillus,  typhoid  bacillus,  colon  bacillus,  influenza  bacillus, 
gonococcus.  and  occasionally  other  organisms  are  found,  but  even  in 
organs  containing  bacteria  the  number  is  rarely  large.  Concerning 
the  changes  that  result  in  nonfatal  cases  we  possess  but  little  accurate 
information.  Baginsky  and  others  believe  that  they  have  been  able 
to  trace  cases  of  chronic  nephritis  to  an  acute  diffuse  lesion  of  the  type 
now  under  consideration.  Certainly  if  intertubular  changes  have  oc- 
curred.—and  they  are  present  in  most  cases.— the  kidney  must  be  left 
correspondingly  damaged;  the  extent  of  the  injury,  however,  must 
vary  widely,  and  no  doubt  the  recuperative  power  of  many  individuals, 
especially  children,  in  whom  the  disease  is  frequent,  is  able  to  establish 
a  physiologic  if  not  structural  normal.  In  no  other  way  can  we  account 
for  the  well-established  clinical  fact  that  many  children  i)ass  through 
an  attack  of  postscariatinal  nephritis  and  never  afterward  manifest 
any  symptoms  indicative  of  renal  lesion.  Others  are  less  fortunate, 
the  affection  terminating  in  a  subacute  or  chronic  diffuse  nephritis 
from  which  recovery  rarely  ensues. 

Among  the  important  lesions  accompanying  acute  nephritis  special 
'  These  bodies  are  described  on  p.  303. 


648  SPECIAL  PATHOLOGY. 

t 

mention  should  be  made  of  dropsy  and  anemia,  both  of  which  are 
extreme.  The  dropsy  involves  the  subcutaneous  tissues  and  may  be 
universal ;  large  fluid  accumulations  frequently  form  in  the  serous 
cavities;  laryngeal  edema  is  sometimes  observed.  These  patients 
occasionally  develop  pericarditis,  pleurisy,  bronchitis,  bronchopneu- 
monia, or  even  a  true  croupous  pneumonia ;  it  is  probable  that  these 
have  no  immediate  connection  with  the  renal  condition  except  such 
influence  as  is  manifested  by  reduced  resistance  to  infection.  Myo- 
cardial degenerations,  and  evidences  of  cardiac  failure,  are  sometimes 
observed;  occasionally  an  acute  nonsuppurative  interstitial  myocar- 
ditis is  present.  It  is  probable  that  the  alterations  in  the  heart  muscle 
are  produced  by  the  same  causes  as  produced  the  nephritis,  and  are 
therefore  independent ;  they  are  no  doubt  intensified  and  their  influence 
prolonged  by  the  concurrent  renal  lesion.  The  clinical  condition  called 
uremia  is  often  present.  The  anemia  of  Bright's  disease  is  of  the  sec- 
ondary type  (see  p.  419). 

The  tirinary  changes  accompanying  acute  nephritis'^  are  not  always 
the  same  and  in  some  cases  are  not  marked.  In  the  earlier  stages  the 
quantity  of  the  urine  is  diminished  and  in  some  cases  actual  suppression 
occurs.  The  urine  secreted  in  small  quantities  is  usually  highly  colored, 
of  a  high  specific  gravity,  and,  from  the  admixture  of  blood,  smoky 
or  darker  in  hue.  In  the  earlier  stage  the  amount  of  albumin  is  usually 
abundant,  and  may  be  so  great  that  when  a  small  test-tube  containing 
the  urine  is  immersed  in  boiling  water,  the  contents  solidify;  the  quan- 
tity of  albumin  becomes  less  as  the  case  advances,  and  later  may  be 
absent,  although  a  microscopic  examination  of  the  urine  continues  to 
show  that  renal  changes  are  still  in  progress.  In  the  beginning  of  the 
attack  the  character  of  the  formed  elements  observed  in  the  urine  is 
determined  by  the  extent  of  the  hyperemia,  the  abundance  of  the  ex- 
udate, and  the  amount  of  renal  necrosis,  degeneration,  and  desquama- 
tion. Casts  are  usually  abundant,  and  may  be  composed  of  epithelium 
or  blood;  later  the  blood  casts  become  less  numerous,  although  epithelial, 
granular,  and  fatty  casts  linger  into  convalescence.  As  recovery  pro- 
ceeds the  epithelium  seen  in  the  casts  improves,  and  eventually  dis- 
appears; a  few  hyaline  casts  continue  for  a  short  time,  but  gradually 
no  more  can  be  found;  the  albumin  slowly  diminishes  and  eventually 
disappears,  the  reduction  in  urea  is  fully  made  up,  and  the  kidney 
resumes  its  normal  functions.  When  the  disease  is  progressing  into 
the  chronic  form,  the  epithelial  cells,  occurring  in  the  casts,  do  not 
return  to  anything  like  their  normal  condition,  but  remain  more  or 
less  granular  and  sometimes  f att}^ ;  the  amount  of  urine  remains  dimin- 
ished, urea  excretion  does  not  rise  to  the  normal,  and  albumin,  in  a 
varying  quantity,  persists. 

Chronic  diffuse  nephritis,^  also  called  chronic  parenchymatous 
nephritis,  chronic  tubular  nephritis,  chronic  catarrhal  nephritis,  chronic 
desquamative   nephritis,    chronic   epithelial   nephritis,   chronic   renal   de- 

'  For  technic  see  chapter  on  Examination  of  the  Urine ;  the  varieties  of  casts 
are  shown  in  the  illustrations  accompanying  that  chapter. 

^  See  Bradford,  "Lancet,"  1901,  vol.  i,  1903,  vol.  ii,  and  1904,  vol.  ii.  Weber, 
'■  Lancet,"  April  26,  1902.  Senator.  "  Deut.  med.  Woch.,"  Jan.  i,  1903.  Forocular 
complications  of  Bright's  disease  see  Strieker,  "Jour,  of  Amer.  Med.  Assoc," 
Feb.  20,   1904. 


DlSliASKS   OK   TllK    URINARY   ORCANS.  64Q 

goienitioii,  and  in  one  form,  large  u'liitc  kidney,  and  in  anolher,  small 
ivhitc  kidm-y,  is  characterized  by  degeneration  of  the  renal  epitheHuin 
and  in  some  cases  marked  interstitial  changes.  It  is  possible  that  it 
is  sometimes  a  se«iuel  of  the  acute  diffuse  nei)hritis;  commonly,  how- 
ever, it  comes  on  insidiously  without  any  distinctly  antecedent  inflam- 
matory disturbance.  In  such  cases  it  has  been  attributed  to  overwork 
of  the  kidney  such  as  occurs  in  beer-drinkers  and  consumers  of  large 
quantities  of  alcohol.  It  is  probably  the  result  of  a  slowly  acting  but 
long-continuing  irritation  incident  to  the  excretion  of  some  toxic  sub- 
stance. It  is  probable  that  different  irritants  are  [)resent  in  different 
cases.  It  is  sometimes  associated  with  chronic  suppuration  and  chronic 
infections,  such  as  tuberculosis  and  syphilis.  The  di-sease  occasionally 
follows  acute  febrile  processes,  and  it  has  been  observed  after  prolonged 
malarial  infection.  A  similar,  apparently  identical  change  accom- 
]>anies  amyloid  disease  of  the  kidney,  and  occasionally  i)arenchymatous 
nephritis  terminates  in  lardaceous  disease.  Chronic  diffuse  nephritis 
is  a  disease  of  young  adults  and  occasionally  of  children. 

Morbid  Anatomy. — It  is  customary  to  recognize  two  forms  of  chronic 
diffuse  nephritis;  in  one  of  these  the  organ  is  large,  pale,  and  anemic, 
and  is  called  the  large  white  or  large  fatty  kidney :  in  the  other  form 
the  organ  is  small,  commonly  firm,  and  is  usually  anemic;  it  is  known 
as  the  small  white  kidney  or  pale  granular  kidney.    (See  Plate  IX,  Fig.  3.) 

The  typical  large  white  kidney  is  of  rare  occurrence;  both  kidneys 
are  involved,  but  not  always  to  the  same  degree;  they  are  very  much 
enlarged  and  ma\-  weigh  twice  the  normal.  Examination  of  the  affected 
organ  shows  that  it  is  pale,  white  or  yellowish-white,  the  capsule  is 
thin  and  mav  appear  edematous;  the  stellate  veins  are  rendered  more 
conspicuous  by  the  pallor  of  the  underlying  tissues,  and  they  also  appear 
enlarged.  Sometimes  the  organ  is  edematous  and  pits  on  pressure;  as 
a  rule,  however,  this  feature  is  absent.  The  renal  tissue  does  not  resist 
incision,  and  the  incised  surfaces  are  usually  pale  and  bloodless.  In 
some  cases,  however,  hemorrhages  into  the  kidney  occur;  this  phe- 
nomenon has  been  attributed  to  fatty  degeneration  of  the  capillary 
walls.  The  cortex  is  enormousl\-  swollen  and  may  be  as  broad  as  the 
medulla.  As  soon  as  incised,  the  capsule  retracts,  the  cortical  portion 
bulges  forward,  and  the  pyramids  often  appear  depressed;  usually  the 
pallor  of  the  medullary  portion  is  less  evident  than  that  of  the  cortex, 
and  sometimes  the  pvramids  are  distinctly  pink.  The  capsule  strips 
readily  and  the  surface  left  behind  is  smooth  and  slightly  mottled. 
Although  great  stress  is  laid  upon  the  size  of  the  organ,  it  is  often  but 
little  enlarged,  and  both  kidneys  are  rarely  affected  to  exactly  the  same 
degree,  although  neither  ever  escapes. 

Histologicallv  the  epithelium  of  the  tubules  will  be  found  in  all 
stages  of  desquamation  and  granular  and  fatty  degeneration.-  Many 
of  the  convoluted  tubes  contain  hyaline,  fatty,  or  granular  casts.  In 
others  the  epithelium  is  absent.  Desquamation  and  degenerative 
changes  are  usuallv  manifest  in  the  epithelium  of  the  tufts.  The  capil- 
laries in  the  Malp'ighian  bodies  are  frequently  the  seat  of  hyaline  de- 
generation and  occasionally  contain  hyaline  thrombi.  The  capsule  of 
Bowman  is  rarelv  normal,  although  the  increase  in  connective  tissue 
is  usuallv  slight.  Sometimes  there  is  marked  intertubular  swelling, 
but,  as  a  rule,  the  interstitial  tissue  contains  but  few  cells.      In  some 


650  SPECIAL  PATHOLOGY. 

cases  the  tendency  toward  interstitial  hemorrhage  is  quite  marked, 
and  in  such  instances  numerous  erythrocytes  may  be  found  between 
the  tubules.  The  areas  of  hemorrhage  are  small,  irregularly  distributed, 
and  never  abundant.  I  have  not  been  able  to  satisfy  myself  that  there 
is  fatty  degeneration  of  the  capillaries,  and  think  that  the  hemorrhage 
is  probably  due  to  increased  arterial  tension  without  provisional  thick- 
ening of  the  capillary  wall,  the  support  of  which  is  lessened  by  the 
degenerative  changes  in  the  renal  parenchyma;  this  type  of  the  affection 
is    sometimes    called    chronic    hemorrhagic    parenchymatous    nephritis. 


-r-fTSf"  1- 


Fig.  320. — Chronic  Parenchymatous  Nephritis,  (i-inch  objective,  i-inch  ocular,  slightly  reduced.) 
Tissue  hardened  in  corrosive  sublimate,  infiltrated  vvfith  paraffin,  and  stained  with  hematoxylin  and  eosin.  a. 
Malpighian  tuft,  containing  an  unusual  number  of  nuclei,  h,  b,  b.  Points  at  which  there  is  some  slight  increase 
in  the  interstitial  tissue.  This  is  not,  however,  at  any  point  marked,  c.  Tubule  containing  granular,  degen- 
erating, epithelial  cells,  which  have  coalesced.  In  many  tubules  the  fragmented  and  desquamated  epithe- 
lial cells  in  all  stages  of  granular  change  are  to  be  seen.  In  no  tubule  are  the  epithelial  cells  normal  or  normally 
arranged,  d.  Tubule  from  which  all  the  epithelium  has  desquamated  and  been  discharged.  e.  Blood-vessel. 
(Kidney  from  a  case  of  tubal  nephritis  that  terminated  in  death  from  eclampsia  at  the  end  of  eleven  weeks 
after  the  appearance  of  the  first  symptoms.) 

The  fact  that  the  toxic  substance  to  which  the  disease  is  due  seems 
to  spend  its  influence  on  the  renal  epithelium  justifies  the  names  given 
to  indicate  this  feature,  such  as  parenchymatous,  tubal  nephritis,  etc. 
There  may  be  some  doubt  as  to  whether  the  change  in  the  epithelium 
is  fatty  degeneration  or  a  necrosis.  Analysis  of  a  large  white  kidney 
has  failed  to  disclose  any  conspicuous  increase  in  the  fat -content  of 
the  organ.  There  seems  to  be  no  doubt  that  the  epithelial  cells  die 
in  large  numbers,  although  there  is  less  certainty  as  to  the  nature  of 


DISEASES  OF   THE   I'klNAKY   OKC.ANS. 


(>5i 


the  ptxn.th>  \>\  which  they  are  destroyed.  If  a  thin  slab  of  such  a 
kidnev  be  exposed  to  the  action  of  osinic  acid,  the  medullary  jjortion 
is  but  sli.v:;htly  darkened,  the  corticomedullary  area  the  least  changed, 
while  tlie  labyrinth  is  rendered  absolutely  black.  Sections  of  a  kidney 
treated  in  this  manner  show  the  epithelial  cells  loaded  with  brownish- 
black  or  black  bodies  indistinguishable  fn^m  fat.  Similar  changes  can 
be  demonstrated  in  tube-casts. 

The  small  ichitc  kithicy  differs  from  the  preceding  in  that  its  surface 
is  granular,  its  capsule  more  adherent,  its  cortex  less  swollen;  indeed, 
the  latter  may  be  thinner  than  that  of  the  normal  organ;  the  kidney 
is  fimi.  and  cuts  with  more  resistance  than  the  normal.  Histologically, 
the  same  tubular  and  tuft  changes  as  those  already  described  in  the 
large  white  kidney  will  be  found  present;  there  is,  however,  a  notable 
increase  in  the  connective  tissue,  more  marked  in  some  places  than  in 
others;  manv  of  the  tufts  will  be  found  fibroid  and  atrojdiied,  and 
manv  of  the  tubules  compressed  or  occluded  by 
contraction  of  the  newly  developed  connective 
tissue. 

If  one  looks  merely  at  the  pathologic  picture 
that  this  type  represents,  he  is  led  to  view  the  con- 
dition as  one  of  chronic  tubular  inflammation,  with 
superadded  interstitial  change.  As  will  be  seen 
later,  there  are  many  of  the  elements  present  that 
are  to  be  noticed  in  the  chronic  interstitial  nephritis. 
and.  as  already  described,  many  of  the  changes 
constantly  associated  with  yjarenchymatous  neph- 
ritis, and  there  is  no  reason,  either  etiologic  or 
anatomic,  for  believing  that  it  is  impossible  for 
the  two  forms  of  nephritis  to  intermingle.  At 
present  this  question  can  not  be  definitely  settled, 
so  that  writers  variously  classify  the  small  white 
kidney,  some  holding  that  it  is  produced  in  .a  way 
entirely  distinct  from  the  chronic  parenchymatous 
or  the  chronic  interstitial,  others  maintaining  that 
it  is  but  a  form  of  the  chronic  parenchymatous  or 
a  tubular  lesion  ingrafted  on  an  interstitial  neph- 
ritis, or  a  parenchymatous  nephritis  that  has  per- 
sisted sufficiently  long  to  develop  fibroid  changes 

in  the  intertubular  connective  tissue.  When  the  kidney  is  considered 
as  a  mucous  membrane,  the  resemblance  between  the  changes  seen  in 
the  submucosa  after  protracted  inflammations  of  the  mucous  mem- 
branes and  the  interstitial  changes  observed  in  the  kidney  subsequent 
to  a  prolonged  inflammatory  lesion  of  the  tubules  become  quite  evident. 

Chronic  diffuse  nephritis  is  almost  invariably  attended  by  dropsy. 
The  edema  may  be  slight  or  quite  marked.  It  is  usually  greater  in 
the  typic  large  white  kidney  than  when  the  organ  is  small  and  flbroid. 
Uremia  is  also  more  common  in  cases  of  large  white  than  small  white 
kidney.  Retinal  lesions  are  less  frequent  than  in  the  chronic  inter- 
stitial nephritis.  Hypertrophy  of  the  heart,  except  in  children,  is  rare, 
although  with  beginning  contraction  the  blood-pressure  is  slightly 
elevated  and  the  muscle  of  the  heart.  [)articularly  of  the  left  ventricle, 
usually  increased.  A  marked  secondary  anemia  is  practically  always 
present. 


Fig.  321.— Kidney,  Chronic 
DiPPCSF.   Nephritis. 

(Jnc-h.alf  normal  si/x-.  Gross 
specimen  treated  with 
.Marihi'srtuid.  .4.  Fatly 
areas  in  the  cortex  largely 
restrict e<l  to  areas,  of  laby- 
rinth. 


652 


SPECIAL  PATHOLOGY. 


Changes  in  the  urine  accompanying  chronic  diffuse  nephritis:  Usu- 
ally the  urine  is  diminished  in  quantity,  and  sometimes  the  secretion 
for  the  twenty -four  hours  does  not  exceed  250  c.c.  In  other  cases 
the  daily  output  approximates  the  normal,  although  a  careful  study 
commonly  demonstrates  that  the  solids  fall  short.  The  specific  gravity 
depends  more  upon  the  quantity  than  upon  other  factors.  Usually 
it  is  lower  than  in  health.  The  quantity  of  albumin  varies,  but  is  com- 
monly large ;  occasionally  the  urine  contains  more  than  the  blood.  The 
urea  excretion  is  practically  always  below  the  normal,  and  is  less  influ- 
enced by  diet  than  is  the  secretion 
from  unaltered  kidneys.  The  other 
urinary  solids  are  also  reduced. 
The  sediment  is  usually  abundant 
and  rich  in  casts,  of  which  the 
granular  and  fatty  types  indicate 
the  character  of  the  change  in  the 
renal  epithelium.  Hyaline  and 
epithelial  casts  containing  leuko- 
cytes, and  occasionally  blood  casts 
are  present;  the  last-named  struc- 
tures are  particularlv  abundant  in 
hemorrhagic  cases.  The  continued 
presence  of  fatty  and  epithelial 
casts  is  the  best  indication  of  per- 
sisting degenerative  changes  in  the 
renal  epithelium.  The  urinary 
changes  of  the  small  white  kidney 
are  less  marked  than  when  the 
renal  lesion  manifests  no  tendency 
to  fibrosis. 

Chronic  interstitial  nephritis/ 
also  called  chronic  productive 
nephritis,  chronic  indurative  neph- 
ritis, contracting  or  contracted  kid- 
ney, granular  kidney,  fibroid  kidney, 
cirrhotic  or  sclerotic  kidney,  gouty 

^  See  Gaucher  and  Sargent,  "Revue 
de  Med.,"  Jan.,  1901.  Nefedieff,  "An- 
nales  de  I'hist.  Pasteur,"  Jan.  25,  1901. 
Herringham,  "Brit.  Med.  Jour.,"  Feb. 
23,  1 90 1.  Claude  and  Burthe,  "  Bio- 
chem.Centralbl.,"  Feb.,  1902.  Cyzhlarz, 
"  Wien.  klin.  Rundschau,"  1902,  No.  16, 
p.  299.  Herrick,  "Jour.  Amer.  Med. 
Assoc,"  Oct.  4,  1902,  p.  S38.  Tschistovitch,  "Bolnitch.  Gaz.  Bot.,"  Oct.  23, 
1902.  Lloyd,  "Proceed,  of  Phila.  Co.  Med.  Soc,"  Nov.,  1902,  p.  291.  Silberstein, 
Inaug.  Diss.,  Berlin,  1903.  Elliott,  "Chicago  Med.  Recorder,"  Oct.,  1903,  p.  239. 
Cassel,  "Berl.  klin.  Woch.,"  1904,  No.  21.  Klineberger,  "Miinch.  med.  Woch.," 
Feb.  3,  1904,  p.  304.  Sawada,  "Deut.  med.  Woch.,"  March  17,  1904.  Beer, 
"Amer.  Jour,  of  Med.  Sci.,"  April,  1904.  Jores,  "Virchow's  Arch.,"  1904,  Bd. 
178,  p.  367.  Rohn,  "Prag.  med.  Woch.,"  1904,  No.  15.  Wilson,  "Lancet," 
Oct.  29,  1904,  p.  1208.  Prym,  "Virchow's  Arch.,"  1904,  Bd.  177,  p.  485.  Hirsh, 
"Amer.  Jotir.  of  Med.  Sci.,"  Jtme,  1904.  Thomson,  "Med.  Record,"  Aug.  20, 
1904,  p.  281.  Nettleship,  "Royal  London  Ophthalmological  Hospital  Reports." 
vol.  xvi,  p.   I. 


Fig.  322. — Kidney  Showing  Chronic  Interstiti.'\l 

Nephritis.     (Natural  size.) 
The  surface  is  granular  and  slightly  lobulated.      The 

process  depicted  in  this  organ  is  not  so  ad\-anced 

as  that  showTi  in  figure  323. 


niSKASKS   tJl-    TllK    UKINAKY   (IKCIAN'S.  65.S 

ktdmy,  rcual  sclerosis,  and  occasionally  hob-iiail  kiiliu-y,  is  a  chronic 
interstitial  intlamniation  of  the  orj^'an  attended  by  a  notable  increase 
in  the  intertubular  and  peri}^domerular  connective  tissue. 

That  the  large  white  kidney,  already  described,  ever  becomes  con- 
verted into  the  kidney  at  present  under  consideration  seems  highly 
improbable,  and  that  the  small  white  kidney  might  eventually  ter- 
minate in  a  fibroid  organ  is  not  likely.  In  a  large  majority  of  cases, 
if  not  in  all.  chronic  interstitial  nephritis  is  ]>rimary.  and  is  not  pre- 
ceded by  any  of  the  lesions  already  considered.  There  may  be  no 
apparent  cause;  heredity  is  a  possible  influence;  continual  excretion 
of  irritant  materials  is  probably  the  most  constant  factor;  exami^les 
of  this  are  to  be  noted  in  alcoholics,  in  sufferers  from  gout  and  lithemia. 
in  chronic  lead-i)oisoning,  and  in  individuals  who  subsist  ujion  a  diet 
composed  largely  of  substances  the  metabolism  of  which  terminates 
in  uric  acid.  Persistent  overwork  of  the  kidney  may  be  placed  among 
the  causes.  As  to  age,  the  ])henomena  of  the  disease  usually  manifest 
themselves  only  in  advanced  life — forty  years  or  later;  the  disease 
is  rare  in  vounger  individuals;  it  is  probable,  however,  that  the  lesions 
begin  much  earlier  than  the  clinical  data  would  seem  to  indicate.  Net- 
tleship  has  been  able  to  collect  80  cases  of  interstitial  nephritis  in 
patients  under  twenty-one  years  of  age,  and  Cassel  describes  an 
hereditary  syphilitic  interstitial  nephritis  occurring  in  children;  Rohn 
has  recorded  a  case  of  unilateral  contracted  kidney  in  an  infant  three 
months  old;  Hirsh's  patients  were  fifteen  and  eighteen  years  respect- 
ively. The  frequency  with  which  chronic  interstitial  nephritis  and 
arteriosclerosis  are  associated,  and  the  fact  that  the  vascular  changes 
wnthin  the  kidney  are  essentially  the  same  as  those  seen  in  the  arteries 
elsewhere,  stronglv  suggest  a  close  connection  between  the  two  con- 
ditions. Gull  and'  Sutton  were  the  first  to  lay  particular  stress  upon 
the  relation  between  the  renal  and  vascular  changes,  and  to  suggest 
that  both  were  part  of  a  single  complex  process.  At  a  meeting  of  the 
American  Medical  Association  in  1904.  Prof.  Welch  exhibited  a  kidney 
the  two  poles  of  which  were  supplied  by  different  arterial  branches; 
one  arterv  showed  arteriosclerosis  and  the  corresponding  pole  of  the 
kidnev  was  granular.  Observers  agree  that  it  is  possible  to  recognize 
a  forrn  of  interstitial  nephritis  consecutive  to  vascular  disease,  and  to 
this  type  has  been  given  the  name  arteriosclerotic  contracted  kidney. 

Morbid  Anato)tiy. — The  kidneys  are  diminished  in  size,  and  may 
weigh  no  more  than  from  100  to  125  grams;  both  organs  may  not  be 
equally  involved.  The  surface  of  the  kidney  is  uneven,  irregular,  and 
indurated,  and  the  capsule  can  not  readily  be  cleared  of  the  perinephric 
fat.  The  organ  is  very  firm,  is  hard  and  slightly  elastic,  and  resists 
cutting  to  such  a  degree  that  it  may  creak  under  the  knife;  the  color 
varies — it  is  usually  red  or  reddish,  or,  when  the  kidney  is  markedly 
anemic,  may  be  somewhat  pale;  it  never  possesses  the  yellowish,  fatty 
appearance'  which  constantly  accompanies  chronic  parenchymatous 
inflammation.  The  capsule  usually  strips  ofi  with  great  difliculty,  and 
it  is  firmlv  adherent  to  the  underlying  tissue,  part  of  which  commonly 
is  brought  away  with  the  caj)sule.'  In  some  cases  the  newly  formed 
fibrous  tissue  is  not  immediately  subcapsular,  and  therefore  does  not 
tie  the  capsule  closely  to  the  organ.  The  capsule  is  markedly  thickened, 
and  immediatelv  under  it  mav  be  found  small    cysts  varying  in  size 


654  SPECIAL    PATHOLOGY. 

from  the  diameter  of  a  pmhead  to  that  of  the  end  of  one's  thumb, 
rarely  larger;  these  cysts  are  near  the  surface,  and  may  be  ruptured 
in  removing  the  capsule.  The  cyst  contents  are  usually  clear  or  slightly 
straw-colored.  In  very  rare  cases  there  may  be  hemorrhage  into  or 
around  the  cvst. 

In  comparing  the  cortex  with  the  medullary  portion  the  observer 
will  be  immediately  struck  with  the  contrast  between  the  condition 
now  being  described  and  the  cortex  in  chronic  diffuse  nephritis.  The 
cortex  is  irregularly  thin,  and  pyramids  are  observed  in  which,  macro- 
scopicallv,  the  medulla  appears  to  extend  to  the  capsule.  Occasionally 
a  pyramid  possesses  its  normal  quota  of  cortex,  thus  illustrating  the 
patchy  character  of  the  lesion;  as  a  rule,  however,  the  cortex,  covering 
all  the  pvramids,  is  more  or  less  contracted.  The  pyramids  are  but 
shghtlv  wasted.     There  is  usually  considerable  fat  in  the  pelvis,  which 

is  less  capacious  than  nor- 
mal. That  the  morbid 
anatomy  of  this  condition 
varies  could  not  be  better 
shown  than  in  figures  322 
and  323,  and  Plate  IX, 
figure  I . 

Histologic  examination 
shows  that  the  lesion  is 
patchy  and  not  universally 
distributed  throughout  the 
cortex;  here  and  there  are 
observed  small  areas  in 
which  the  changes  are  most 
marked;  at  other  points 
the  structural  alterations 
are  inconspicuous.  The 
fibrous  tissue  is  notably  in- 
creased in  the  labyrinth, 
less  so  in  the  pyramids  of 
Ferrein,  and  the  medullary 
portion  is  changed  least  of 
all.  Between  the  tubules, 
in  the  interstitial  connec- 
tive tissue  of  the  organ,  the  fibrous  tissue  hyperplasia,  in  various  stages 
of  development,  is  encountered;  the  more  recent  cellular  accumula- 
tions are  composed  of  lymphoid  cells.  Where  organization  is  in 
process,  the  round  mononuclear  cells  will  be  seen  gradually  forming 
into  spindle-shaped  elements,  through  the  activity  of  which  fibrous 
tissue  is  eventually  produced.  Silberstein  has  shown  that,  like  other 
productive  interstitial  inflammations,  renal  sclerosis  is  attended  by  an 
increase  in  the  elastica  of  the  organ.  The  newly  formed  cicatricial 
tissue  contracts  and  presses  upon  the  blood-vessels,  Malpighian  tufts, 
and  tubules,  therebv  lessening  the  blood  supply,  the  nutrition,  and 
the  functional  activitv  of  these  structures.  The  capsules  of  the 
glomeruli  are  thickened  by  the  progressive  fibrosis,  and  the  contrac- 
tion of  the  newly  formed'  fibrous  tissue  and  hyaline  change  in  the 
capillaries  lead  to  destruction  of  the  tuft.     Glomeruli  whose  vascular 


Fig.  323. 


-Kidney    Showing  Advanced  Chronic   Interstitial 
Nephritis.     (Natural  size.) 
A.  Ureter.     B.  Small    cyst    just   under   capsule.     The    irregularly 
lobulated,  coarsely  and  finely  granular  surface  is  well  show-n. 


Plate  IX. 


Fig.  I. 

Kidney.  Chronic  Interstitial 
Nephritis.  See  p.  653.  {Atlcs  of 
Pathology,     .Sydenham     Society.) 


Fio.  2. 

Part  of  Kidney,  Subacute 
Diffuse  Nephritis.  See  p.  645. 
From  girl  bh  years  old.  Scarlet 
fever  ;  death  on  the  forty-seventh 
day.  More  advanced  degenerative 
change  than  in  Fig.  4.  {Atlas  0} 
Pathology,  Sydenham  Society.) 


-.^^ 


Fig.  3. 

Kidney,  Chronic  DitTuse 
Nephritis.  See  p.  640.  (Atlas 
iif  Pathology,  Sydenham  Society.) 


Fig  .    . 

Part  of  Kidney,  Acute  Diffuse 
Nephritis.  Seep.  645-  From  boy 
q  years  old.  Scarlet  fever  ;  death 
on  the  twenty-second  day  of  the 
disease.  The  initial  stage  of 
engorgement  is  no  longer  present. 
(Alias  oj  Pathology,  Sydenham 
Society.) 


DISEASES  OF  TIIK    lUINAUV   ()K(;A\>.  655 

supplv  is  Still  normal  possess  thickened  capsules;  the  thickeninj^  of 
Bowman's  membrane  is  continuous  with  the  thickened  membrana 
propria  of  the  tubule.  The  epithelium  of  the  tubules  shows  various 
chanijes  dependent  ujion  the  influence  of  the  interstitial  deposit  within 
anv  given  area.  The  large,  swollen,  granular,  fatty,  tortuous  tubules  of 
parenchymatous  nejdiritis  are  not  encountered;  in  those  areas  in  which 
the  new  ti.ssue  is  most  rapidly  organizing  the  tubules  are  diminished 
in  size.  Tubular  narrowing  in  one  area  may  give  rise  to  dilatation 
in  another,  and  bv  progressive  widening  terminate  in  the  formation 
of  the  cvsts  already  described  when  discussing  the  gross  anatomy  of 
the  lesion.     Cornil  and    Ranvier  as.serted  that  such  cysts  might  arise 

.•    ^'  .     v'       ■    -'    '«      "■  — «     ■*'  ''■'-■<    * 

■  r--  ■     ■   '        ■  -      '  ■'> 


b' 

^S«J 

WSi 

m 

ItTO^ 


.  324,— KiDNKY.  Chroxic  I.ntkrstiti.xl  .Xkphritis.     (i-inch  <>l)jecti\ 


Fig.  324.— KiDSKY.  Chroxic  I.ntkrstiti.xl  .Xkphritis.  (i-inch  <>l)jectivc,  i-inch  otiilur.  ^liKhily  reduced.) 
Specimen  fLxcd  in  corrosive  suMimale.  intiltrated  with  p;iralVin.  and  stained  with  hemaloxyhn  and  eosin.  ij.  Slighlly 
thickened  cajwule.  b,  b',  b"  and  a  Ixmnd  the  area  of  most  marke<i  interstitial  change.  althouKh  an  inirea.se 
of  the  interstitial  ti.s.sue  is  evident  Ix-lween  h"  and  <".  .\lx)ut  one  centimeter  10  the  left  of  (/  is  seen  a  lieKinninK 
cy.st.  In  the  area  of  most  marked  interstitial  change  are  a  numl)er  of  degenerating  Malpighian  tufts,  while 
but  a  few  of  the  tubules  are  recognizable.  The  new  lis.sue  is  not  yet  fully  develo|x'd.  but  al  points,  as  around 
the  cyst  d,  .shows  [lartial  conversion  into  fibrous  li.s.sue. 

from  the  Malpighian  tufts — a  view  which  has  been  corrol)orated  by 
later  studies,  especially  by  Beer.  The  condition  is  termed  cystic  atrophy 
of  the  glomeruli.  In  the  glomerular  cysts,  shrunken  fragments  of  the 
tuft  are  sometimes  found  still  attached  to  the  inclosing  wall.  Where 
the  tubule  is  subjected  to  the  damaging  influence  of  contraction,  the 
epithelium  is  atrophied  and  finely  granular,  and  the  cells  are  greatly 
diminished  in  size;  where  the  fluids  are  retained  within  the  tubule 
bv  obstruction  below,  the  epithelium  is  flattened,  hyaline,  granular, 
or  even  fatty.  Occasionally,  tube-casts  may  be  seen  in  situ:  if  the 
epithelium  or  interstitial  tissue  be  pigmented,  it  is  probably  the  result 


656 


SPECIAL  PATHOLOGY, 


of  previous  hemorrhage.  The  blood-vessels  of  the  kidney  manifest 
changes  indistinguishable  from  those  observed  in  similar  structures 
elsewhere. 

The  urine  is  increased  in  quantity,  light  in  color,  and  may  be  almost 
colorless;  its  specific  gravity  is  rarely  over  1012  or  1015,  and  may 
fall  as  low  as  1005;  albumin  is  present  in  varying  amounts;  sometimes 
the  albumin  may  be  scanty  and  may  escape  detection,  or,  for  short 
periods,  rarely  long,  it  may  be  entirely  absent;  as  a  rule,  there  is  no 
sediment,  and  the  dissolved  solid  constituents — salts  and  urea — are 
diminished.  The  casts  found  are  usually  hyaline ;  they  are  not  abundant 
and  not  constantly  present;  during  acute  exacerbations  in  the  inflam- 
matory processes  the  phenomena  of  nephric  hyperemia  may  be  observed. 


Fig.  325. — Kidney,  Chronic  Interstitial  Nephritis. 
A.  Part  of  capsule.     B.  Malpighian  body,  showing  advancing  granular  and  hyaline  changes  with  marked  thick- 
ening of  the  capsule.     C,  C,  C.  Tubules  in  the  niidst  of  the  newly  formed  connective  tissue;    the  epithelium 
is  wasted  or  absent  and  the  tubular  wall  notably  thickened.     The  larger  tubes  on  the  left  and  below  are  some- 
what dilated. 


Changes  Oceurring  in  Other  Structures. — Clinicians  have  long  known 
that  the  arterial  tension  is  raised,  at  least  in  the  earlier  stages  of 
chronic  interstitial  nephritis,  and  more  recently  Czyhlarz,  Sawada,  and 
others  have  studied  the  elevated  tension  by  instrumental  methods. 
Czyhlarz  believes  that  he  has  been  able  to  show  that  with  improve- 
ment the  arterial  tension  falls,  and  rises  again  during  relapses.  It 
is  not  certain,  however,  that  the  alteration  in  tension  may  not  be  due 
to  the  vascular,  rather  than  the  renal,  lesion.  Cardiac  hypertrophy  is 
constantly  present  prior  to  degenerative  or  arteriosclerotic  changes  in 
the  myocardium,  after  which  dilatation  occurs.  As  a  result  of  the 
accumulation  of  toxic  products,  uremic  phenomena  are  not  infrequent; 
these  may  be  manifested  by  symptoms  referable  to  the  vascular  and 


DISEASES  OF  THE    URINARY   ORGAN'S. 


657 


toxemic  influences  on  the  central  nervous  system,  or  by  less  definite 
nervous  symptoms  which  Lloyd  refers  to  as  hysteric  or  neurasthenic. 
Neuritis  is  occasionally  observed,  de  vSchweinitz^  describes  with  detail 
the  retinal  lesions  to  which  the  term  albuminuric  retinitis  is  commonly 
applied.  The  vessels  of  the  retina  may  be  the  seat  of  recognizable 
arteriosclerotic  chanties.  According  to  Nettleship,  the  earliest  age  at 
which  renal  retinitis  has  been  ol)served  is  five  years. 

Lardaceous  disease  of  the  kidney  arises  in  connection  with  general 
amvloid  disease.  (See  ]>.  227.)  The  process  is  frequently  associated 
with  a  more  or  less  fully  developed  chronic  parenchymatous  nephritis, 
of  the  kind  already  described. 

Morbid  Anatoiny. — In  many  cases  the  kidney  is  considerably  in- 
creased  in   size;    occasionallv  it  may  not  be  larger  than  the   normal; 


Fig.  326. — KiD.VEY,  Chro.vic  LsTtusTiTiAL  NtPHRins  ANU  Lardaceous  Disease. 
Specimen  specially  stained  by  gentian-\nolct.      .4.  The  thickened  capsule  of  a  Malpighian  tuft;    the  interstitial 
tissue  at  all  points  in  the  field  is  notably  increased.     B.  In  that  port  of  the  tuft  King  to  the  right  and  below 
the  tuft  pedicle,  and  indicated  by  the  faint  leader  from  B,  the  opaque  lardacein  can  be  seen. 

in  rare  instances  the  organ  is  small.  The  veins  of  the  capsule  are  dilated, 
the  surface  is  smooth,  and  the  organ  is  firm,  but  does  not  appear  fibroid. 
The  tissue  cuts  with  more  resistance  than  in  uncomplicated  chronic 
parenchvmatous  nephritis;  the  cortex  is  much  thickened,  is  glistening 
or  hvaline,  is  slightly  swollen,  and  the  Malpighian  tufts,  in  which  the 
lesion  is  most  manifest,  may  be  readily  picked  out.  The  pale,  hyaline, 
or  semitranslucent  cortex  contrasts  ^^^th  the  deep-red  or,  at  times, 
almost  purplish,  or  beefy,  medullary  portion;  the  usual  tests  for  lar- 
dacein readily  demonstrate  the  character  of  the  lesion. 

The  urine  is  usually  abundant,  pale,   clear,  and  of  a  low  specific 
gravity;    albumin  and    also  hyaline,  granular,  or   fatty  casts  are   fre- 
'  "Proc.  Phila.  Co.  Med.  Soc.,"  Nov.,  1902,  p.  298. 
43 


658  SPECIAL  PATHOLOGY. 

quently  present,  and,  occasionally, — not  constantly,  as  commonly  be- 
lieved,— waxy  casts  which  may  give  the  amyloid  reaction.  The  changes 
in  other  organs  and  tissues  are  dependent  upon  the  general  amyloid 
infiltration  or  upon  the  character  of  the  accompanying  renal  lesion. 
If  the  condition  be  attended  by  diffuse  nephritis,  dropsy,  edema, 
etc.,  may  be  present;  if  the  accompanying  lesion  be  an  interstitial 
nephritis,  which  is  rare,  the  vascular  and  other  phenomena  of  that 
condition  may  be  manifest. 

Pyelitis^  is  an  inflammation  of  the  pelvis  of  the  kidney.  It  may 
be  acute  or  chronic ;  primary  or  secondary — rarely  the  former.  It  may 
result  from  extension  of  an  infection  from  the  kidney,  but  more  com- 
monly it  is  the  cause  of  inflammation  extending  into  the  medulla  or 
the  cortex.-  Inflammation  of  the  renal  pelvis  is  usually  the  result  of 
infection  by  bacteria  excreted  by  the  kidney;  in  other  words,  it  is 
indirectly  of  hematogenous  origin.  The  belief  that  infections  of  an  as- 
cending type,  secondary  to  disease  of  the  bladder,  are  of  common 
occurrence,  is  less  popular  than  formerly.  The  experiments  of  Sampson 
seem  to  indicate  that  overdistention  of  the  bladder  never  gives  rise 
to  dilatation  of  the  ureters;  this,  however,  does  not  disprove  the  pos- 
sibility of  inflammation  extending  along  the  course  of  the  continuous 
mucosa.  The  bacteria  commonly  found  are  the  typhoid  bacillus,  the 
colon  bacillus,  and  the  pyogenic  cocci.  Wright  reported  a  case  in 
which  the  influenza  bacillus  was  present  with  other  organisms.  The  com- 
bined statistics  of  several  observers  show  that  the  colon  bacillus  occurs 
in  about  83.5  per  cent,  of  the  cases.  Pneumococcal  forms  have  been 
described.  Probably  the  most  important  factor  in  the  production  of 
pyelitis  is  ureteral  obstruction.  Kinks,  inflammatory  conditions,  or 
external  pressure,  producing  accumulations  of  urine  in  the  pelvis  of 
the  kidney,  are  commonly  followed  by  pyelitis.  It  is  now  generally 
believed  that  the  pyelitis  of  pregnancy  results  from  obstruction 
due  to  pressure  on  the  ureter  by  the  gravid  uterus.  The  pyelitis  of 
infants  is  probably  due  to  some  congenital  abnormality  that  produces 
temporary  urinary  stasis.  Among  the  rare  causes  of  inflammation  of 
the  pelvis  of  the  kidney  may  be  mentioned  perinephritis  and  inflam- 
mations around  the  ureter  (periureteritis)  and  morbid  growths  invading 
the  affected  structures.  Stone  in  the  kidney  (nephrolithiasis)  is  com- 
monly given  as  a  cause  of  pyelitis,  but  it  is  probable  that  stone  is  a 
sequence  of  pyelitis,  and  not  the  reverse.  It  is  said  that  the  adminis- 
tration of  turpentine,  cantharidin,  and  other  irritating  agents  may 
produce  inflammation  of  the  renal  pelvis. 

The  inflammation  may  be  catarrhal,  pseudomembranous,  suppura- 
tive, or  hemorrhagic;     rarely  it  is  gangrenous.     The  first  three  forms 

'  Brown,  "Johns  Hopkins  Hospital  Reports,"  vol.  x,  Nos.  i  and  2.  Caro, 
"Deut.  med.  Woch.,"  April.  1901.  Thomson,  "Edinburgh  Obstet.  Soc,"  April 
4,  1902;  also  "Brit.  Med.  Jour.,"  Ma^'  31,  1902,  p.  133S.  Hartwig,  "  Berl.  klin. 
Woch.,"  Nov.  20,  1903.  Bazy,  "La  Presse  Med.,"  Dec.  30,  1903,  p.  893.  Haber- 
lin,  "Miinch.  med.  Woch.,"  Feb.  2,  1904,  p.  198.  Cathala,  "These  de  Paris," 
1904.  Sampson,  "Johns  Hopkins  Hosp.  Bull.,"  1903,  vol.  xiv.  p.  334.  Cragin, 
"Med.  Record,"  July  16,  1904,  p.  81.  Rochard,  "La  Presse  Med.,"  Nov.  16,  1904, 
p.  729.  Spalding,  "Jour,  of  Obst.,"  Feb.,  1905.  Wright,  "Boston  Med.  and 
Surg.  Jour.,"  April  27,  1905,  p.  496.  Elliott,  "Med.  News,"  Aug.  20,  1904,  p. 
357.      Keyes,  "N.  Y.  Med.  Jour.,"  Aug.  27,  1904,  p.  397. 

-See  Acute  Suppurative  Interstitial  Nephritis,  p.  641. 


DISEASES  Ol'    THE    URINARY  (tRCANS.  659 

iiuiy  l)e  acute  or  chronic;  the  last  two  are  usually  acute,  hut  may  be 
engrafted  upon  one  of  the  chronic  forms.  The  inflammation  mav 
partake  of  some  of  the  characters  of  the  acute  infectious  disease  with 
which  it  is  associated;  thus,  gonorrheal  pyelitis  is  commonly  sui)pura- 
tive.  I  have  seen  meml)ranous  pyelitis  accomj)any  diphtheria  and 
also  typhoid;  with  the  last-named  disease  hemorrhagic  forms  some- 
times occur.  If  ureteral  obstruction  takes  place,  dilatation  of  the 
pelvis  and  pressure  atrophy  of  the  kidney  give  rise  to  a  sac  in  which 
the  purulent  matter  and  altered  secretions  accumulate;  the  condition 
is  called  pyonephrosis,  and  may  also  result  from  infection  of  a  hydro- 
nephrosis. The  lluid  contained  in  the  sac,  which  may  be  loculated  and 
composed  of  several  pouches,  often  ajjpears  to  be  almost  pure  ])us, 
although  usually  urine  is  present  and  sometimes  blood.  Calculi  which 
have  preceded  the  suppurative  process  may  also  be  found.  The  changes 
in  the  renal  tissue  depend  upon  the  duration  and  character  of  the 
inflammation  and  also  upon  whether  actual  infection  of  the  kidnev 
substance  has  occurred.  The  lesions  of  acute  suppurative  nephritis 
may  be  present  or  the  renal  parenchyma  may  be  thinned  and  Hbroid 
and  contain  no  foci  of  pus-formation.  Sometimes  no  macroscopically 
perceptible  kidney  tissue  is  present.  The  condition  may  be  attended 
by  a  perine])hritis  (see  p.  634). 

Nephrolithiasis  is  a  name  applied  to  a  condition  in  wliich  stones  are 
present  in  the  kidney.  In  size  such  bodies  vary  from  tine  granules 
deposited  in  the  tubules  to  large  masses  that  till  the  renal  pelvis;  Shield 
reported  a  renal  calculus  weighing  485  gm.  The  stone  may  be  solitary, 
or  calculi  may  be  present  in  large  numbers.  Bland-Sutton^  reports 
an  instance  in  which  40,000  iridescent  calculi  were  contained  in 
a  single  kidney.  Renal  stones  are  usually  composed  of  uric  acid 
or  urates,  oxalate  or  phosphate  of  lime,  and  less  frequently  carbon- 
ates, cystin  and  xanthin.  and  rarely  indigo.  Each  concretion  usually 
possesses  a  nucleus  surrounded  by  lamellae,  all  of  which  mav  not  be 
of  the  same  chemic  composition.  Ova  of  the  Bilharzia  haematobia 
may  constitute  the  nucleus.  Frequently  the  nuclei  contain  bac- 
teria, and  some  observers  maintain  that  germs  are  the  essential  cause 
of  calculus  formation.  This  contention  is  supported  by  the  well- 
known  frequency  with  which  microorganisms  are  responsible  for  the 
production  of  gall-stones.  Obstruction  to  the  ureter  and  inflammation 
of  the  pelvis  of  the  kidney  favor  the  development  of  calculi.  Such 
stones  are  called  secondary  calculi.  It  is  sujtposed  that  nephro- 
lithiasis may  occur  without  any  preceding  inflammation  of  the  pelvis 
of  the  kidney,  and  stones  thought  to  have  this  origin  are  termed 
primary  calculi. 

Calculi  arising  in  the  pelvis  of  the  kidney  may  obstruct  the  ureter 
and  give  rise  to  retention,  or  by  favoring  colonization  of  pyogenic 
bacteria  induce  suppurative  pyonephrosis  or  pyelonephritis  which  may, 
in  some  cases,  become  gangrenous.  More  or  less  hematuria  accom- 
panies the  presence  of  stones  in  the  renal  pelvis,  and  some  observers 
maintain  that,  in  all  cases,  a  careful  search  will  disclose  the  presence 
of  red  blood-cells  in  the  urine.  It  is  possible  that  loculated  calculi 
(those  deflnitely  inclosed  in  a  renal  pouch)  are  infrequent  causes  of 
hemorrhage. 

Ureteritis,  or  inflammation  of  the  ureter,  probably  results  from 
''"Brit.   Med.    four.."    Ian.    ;i.    loo;.  p.    J2>. 


66o  SPECIAL  PATHOLOGY. 

essentially  the  same  causes  as  pyelitis,  and  may  be  a  continuation  of, 
or  antecedent  to,  the  latter.  Occasionally  inflammation  begins  at  the 
cystic  end  of  the  ureter  and  is  secondary  to  inflammation  of  the  bladder. 
The  well-known  frequency  with  which  bacteria  occur  in  the  urine 
(bacteriuria)  accounts  for  man}-  of  these  cases.  Traumatic  forms  are 
rare;  ureteritis  due  to  disease  of  the  prostate  or  ureteral  orifice  is  of 
frequent  occurrence.  The  inflammation  may  be  acute  or  chronic,  and 
may  first  affect  the  mucosa  or  the  ureteral  wall,  and  from  either  involve 
the  contiguous  tissues,  causing  periureteritis.  The  acute  form  of  the 
affection  mav  be  catarrhal,  pseudomembranous,  suppurative,  or  gan- 
grenous; fibrinous  casts  of  the  ureters  are  sometimes  voided.  When 
the  inflammation  is  of  long  duration,  great  thickening  of  the  ureteral 
wall  and  stricture  formation  may  occur.  A  cystic  ureteritis/  due  to 
central  degeneration  and  fluid  transudation  into  v.  Bruns'  cell-nests, 
has  been  described.  The  resulting  cysts  resemble  miliary  tubercles  and 
may  give  rise  to  obstruction.  Strictures,  kinks,  and  valve-like  forma- 
tions may  produce  ureteral  obstruction  and  give  rise  to  cystic  dilatation 
on  the  renal  side  of  the  lesion,  which  will  be  further  discussed  with 
hydronephrosis. 

Tuberculosis  is  not  an  infrequent  form  of  ureteral  disease  and  will 
be  considered  with  tuberculosis  of  the  kidney. 

Tuberculosis  of  the  kidney-  may  be  primary  or  secondary.  The 
primary  form  is  rare.  Morris  has  been  able  to  collect  15  such  cases 
in  2610  autopsies.  Infection  may  occur  from  the  blood  or  by  an  ascend- 
ing tuberculosis  which  was  primary  in  the  lower  passages.  In  the 
discussion  of  the  German  Surgical  Congress  in  1901,  Baumgarten 
doubted  the  frequency  of  ascending  infections,  and  it  is  generally  con- 
ceded that  tuberculosis,  involving  the  genito-urinary  organs,  usually 
begins  in  the  kidney.  It  has  been  shown  by  a  number  of  observers 
that  in  patients  suffering  from  active  tuberculosis^  the  bacilli  may  be 
secreted  in  the  urine. 

In  acute  miliary  tuberculosis  the  kidney  in  common  with  other 
organs  frequently  contains  large  numbers  of  tubercles.  These  bodies 
possess  the  usual  characters  of  miliary  tubercles  observed  elsewhere 
(see  p.  149).  In  other  cases  the  kidney  contains  a  single  caseous  nodule 
surrounded  by  fibrous  tissue  which  is  sometimes  calcareous ;  rarely  such 
masses  are  bilateral  and  multiple  in  both  organs.  In  the  so-called 
massive  tuberculosis  of  the  kidney  practically  the  entire  organ  is  con- 
verted into  caseous  material.  This  form,  more  frequently  than  the 
preceding  types,  is  accompanied  by  tuberculosis  of  the  pelvis  and  ureter 
and  may  involve  the  bladder.  The  organ  is  often  greatly  enlarged, 
and  may  be  the  size  of  a  fetal  head;  the  capsule  is  usually  thickened 
and  the  perinephric  fat  sclerosed.  In  some  cases  tuberculous  peri- 
nephritis accompanies  the  renal  lesion.  Usually  this  form  is  unilateral 
and  the  opposite  kidney  is  not  infrequently  amyloid.  Often  the  dis- 
charge of  caseous  material  obstructs  the  ureter,  or  ureteral  stenosis 
results  from  tuberculosis  of  the  ureteral  mucosa.     In  such  cases,  par- 

^  See  Carey  and  Laird.  "Albany  Med.  Annals,"  Jvdy,  1904;    bibliograph}-. 

^  The  important  literature  on  the  subject  is  given  by  Douglas,  "Surgical  Dis- 
eases of  the  Abdomen,"  1903,  p.  552. 

'Flick  and  Walsh,  "Proceed,  of  Path.  Soc.  of  Phila.,"  April,  1903,  p.  149; 
see  also  discussion,  p.  154. 


DISEASES   OF  THE   UHIN'AUY   ORGAN'S. 


66  I 


ticularly  if  mixed  infection  he  present,  the  rescnil)hince  to  py()nei)hrosis 
is  striking.  Israel'  states  that  in  thirty-three  j^er  eent.  of  the  cases 
of  pNxHtis  with  retention  of  ])us  tuberculosis  of  the  affected  organ 
complicates  the  primary  lesion.  Chronic  caseous  tuberculosis  of  the 
kidnev  is  often  latent  and  fretjuently  comes  to  autopsy  undiaj^mosticated. 

Syphilis  of  the  kidney,  manifested  by  distinct  lesions,  is  of  infre- 
quent occurrence.  Syphilitics  in  whom  the  tertiary  phenomena  are 
active,  mav  have  amyloid  disease  of  the  kidney,  and  durinj,'  the  secondary 
stage  true  syphilitic  nephritis  sometimes  occurs.  The  arterial  lesions 
due  to  syi)hilis  may  affect  the  kidney,  giving  rise  to  a  form  of  arterio- 
sclerotic contraction. 
Gummata  of  the  kidney 
are  rare,  and  when  pres- 
ent possess  the  usual  char- 
acters of  the  syphiloma. 
(See  p.  179.) 

Leprosy  rarely  gives 
rise  to  distinctive  altera- 
tions in  the  kidney;  pa- 
tients affected  with  the 
disease  not  infrequentl\ 
develop  nephritis,  proba- 
blv  due  to  the  continuou> 
secretion  of  irritants  re- 
sulting from  lesions  out- 
side the  kidney. 

Tumors  of  the  kidney 
are  not  common.  Of  151) 
cases  collected  by  Morris. 
63  were  sarcomata,  41 
carcinomata;  his  list  a.h<> 
includes  21  instances  of 
cystic  degeneration  and  1 1 
hydatid  cysts;  there  were 
10  adenomata.  Of  the 
sarcomata,  seventy-five  per 
cent,  occur  in  infancy;  oc- 
casionally they  are  con- 
genital and  may  obstruct 
labor.  Some  of  the  sar- 
comata are  histologically 
extremely  complex,  often 
containing  structures  that 

suggest  adenoma  or  carcinoma,  and  have  been  called  adenosarcomata 
of  the  kidnev.  Birch-Hirschfeld  has  especially  called  attention  to  such 
neoplasms.^  .■\n\iio)uata,  Iciomyomata ,  and  rhahdomyomata  of  the  kidney 
are  rare.  Angiomata  have  been  observed:  they  sometimes  involve  the 
pyramids  or  the  pelvis,  and  may  give  rise   to  troublesome  hemorrhage. 


l-iG.  327.— Tuberculous  Pvelonephritis;  Chro.vic  Tuberculosis 

OF    THE    KlD.VEY. 

Specimen  shows  cavities  in  medullary  and  cortical  portions  of  the 
organ,  due  to  the  extension  of  tuberculosis  from  the  pelvis. 


'  "Deut.  med.  Woch.,"  vol.  xxiv.  p.  .\^2. 
-  .Mharran  and  ImViert.  "Tunieurs  du  Rein."   igo.?. 
'  See  also  Strong.  "Arch,  of  Pediatrics."  May,  1003.  p 
Med.  Annals,"  Aug.,   iqo^,  p.  444- 


All.allV 


662 


SPECIAL  PATHOLOGY. 


Papilloma^  of  the  pelvis  of  the  kidney  may  be  extremely  small,  but 
attended  by  hemorrhages  that  prove  fatal ;  it  is  usuallv  of  the  villous 
type. 

Probably  the  most  frequent  tumor  of  the  kidney  is  the  hyperne- 
phroma, a  neoplasm  arising  from  ectopic  adrenal  tissue.  Of  the  163 
hypernephromata  collected  by  Ellis, ^  157  were  in  the  kidney.  There 
is  no  special  predilection  for  either  side;  the  tumors  are  usually  soft, 
sometimes  cyst-like.  The  neoplasm  is  often  sharply  outlined  from  con- 
tiguous tissue,  and  usually  possesses  a  capsule.  Some  give  rise  to 
metastasis,  others  do  not,  and  it  has  been  suggested  that  benign  and 
malignant  hypernephromata  be  recognized.  Histologically  these  neo- 
plasms  are   composed   of   cells   resembling  those   seen  in  the   adrenal ; 


Fig.  328. — Hypernephroma.     (Case  Reported  by  Keen.) 
A.  Capsule  of  kidney  over  tumor.     B.  Areas  of  hemorrhage. 


they  usually  contain  a  fairly  uniformly  distributed  stroma,  which  in 
many  areas  is  scant  and  often  extends  into  relatively  large  spaces, 
indicating  that  under  certain  conditions  it  is  ruptured  or  in  other  ways 
disappears  before  the  rapidly  growing  cell.  Such  extensions  of  the 
stroma  are  covered  by  the  large  vesicular  neoplastic  cells,  giving  rise 
to  a  picture  resembling  that  of  papillary  adenoma.  Hemorrhage  in 
the  interior  of  the  tumor  is  not  uncommon. 

'Butte,  "Virchow's  Arch.,"  1901,  Bd.  164.  Savory  and  Nash,  "Lancet," 
Dec.  17,  1904,  p.   1699. 

^  For  detailed  studv  of  these  neoplasms  and  references  to  literature  see  Keen. 
Pfahler  and  Ellis,  "Amer.  Med.,"  Dec.   17,   1904. 


niSKASES  OF  THE    L'klNAkY   OKCAN'S. 


663 


Paranephric  tumors'  arc  rarely  primary;  they  may  be  due  to  ex- 
tension from  (.-ontis.'uous  structures,  especially  the  kidney  or  adrenal. 

Cysts  of  the  Kidney. — Retention  cysts  of  the  renal  tuVjules  occurring 
in  contracted  kidiuv  were  considered  with  interstitial  nej^hritis.  In 
the  cortex  they  are  commonly  small,  although  they  may  be  as  large  as 
the  end  of  one's  thumb,  rarely  larger.  They  are  usually  multiple  and 
result  from  occlusion  of  the  tubules  with  dilatation  above  the  obstruc- 
tion, or  from  cystic  atrophy  of  the  tufts. 

Hydronephrosis-  is  a  condition  resulting  from  ureteral  obstruction, 
and  is  characterized  by  more  or  less  distention  of  the  renal  pelvis  and 
coincident  atrophy  of  the  medulla  and  cortex.  The  affection  may  be 
congenital  or  due  to  developmental   abnormalities,  such  as  jjartial  or 


•^u'AA- 


Cif^- 


.fei 


.-=-  :    ♦-  - 


>t/^. 


';^V 


:/} 


'?^ 


<*^, 


':&: 


'A-t 


Fic.  329. — Section  of  Hypernephroma,  Showing  Capsule. 
A  to  A.  Ciir-ulc.     H.  Blood-vos-stl  in  capsule.     C.  .•Vlveolus  surrounded  by  polyhedral  cells,  m.iny  of  which  are 
polymorphous  and  possess   the  general    characters  of   the   cells  found  in   the  adrenal    cortex.     D.  Typical 
sponKiocste.     E.  Connective-ti.'vsue  reticulum. 


complete  atresia  of  any  part  of  the  conducting  passage.  Many  writers 
lav  great  stress  upon  oblique  or  valve-like  junction  between  the  ureter 
arid  renal  pelvis  as  a  cause  of  hydronephrosis;  the  condition  may  be 
produced  by  tortuosity  and  kiiiks  of  the  ureter.  Strictures  of  the 
urethra  or  ureter,  and  renal  or  ureteral  calculi,  may  also  give  rise  to 
hydronephrosis.  Tumors  involving  the  ureter  or  its  orifice  in  the 
bladder,  or  neoplasms  pressing  upon  the  duct,  may  also  produce  reten- 
tion. Prolapsed  or  floating  kidneys  not  uncommonly  show  moderate 
degrees  of  hydronephrosis.     The  amount  of  distention  and  consequent 

'  Rambaud.  "'Th^se  de  Toulouse,"  1Q04. 

-  Riesman,  'Proceed,  of  Path.  Soc.  of  Phila.,"  July  15.  189S,  p.  253.     Bazy, 
•Rcvvie  de  Chir.."  Jan.  to.  1903.  and  'La  Presse  Med."  Aug.  3,  1904,  p.  489. 


664 


SPECIAL  PATHOLOGY. 


size  of  the  affected  organ  are  largely  influenced  by  the  completeness 
and  persistency  of  the  obstruction.     If  the  ureter  be   ligated,   or  in 


Fig.  330. — Section  of  Hyperxephroma,  Showing  Character  of  Cells.    S.vme  Section  .\s  Fig.  329.     (Zeiss 

2  mm.  homo,  im.) 
.\.  Blood-vessel.     B  and  C.  Spongiocytes.     In  the  upper  cell  (B)  the  intraprotoplasniic  spaces  appear    empty; 

the  corresponding  areas  in  the  lower  cell  (C)  contain  faindy  acidophihc  fine  granules.     D.  Similar   cell,  with 

structureless  clear  protoplasm. 

other  ways  suddenly  occluded,  renal  atrophy  without  notable  increase 
in  the  size  of  the  organ  commonly  occurs.     If,  however,  the  obstruction 


Fig.  331. — Hydronephrosis. 

Kidney  laid  open,  showing  both  halves.    \  few  small,  calcareous  nodules  in  the  pelvis.    (From  a  photograph  made 

by  Dr.  I.  W.  Blackburn,  to  whose  courtesy  the  writer  is  indebted  for  the  use  of  the  illustration.) 


develops  slowly,  or  is  intermittent  in  its  action,  cysts  of  very  great 
size  may  result.     Infection  may   convert   the   hydronephrotic   kidney 


niSKASRS   or   THK    urinary   ORGAN'S. 


665 


into  a  pyonephrosis.  Morris  includes  pyonephrosis  and  hydronephrosis 
under  the  term  renal  distention  or  nephrectasis. 

Hydatid  cysts'  of  the  kidney  are  inlrenuent.  Of  Lyon's  241  cases 
of  echinococcal  (hscase  in  America,  in  9  the  kidney  was  involved.  The 
left  kidnev  is  affected  nearly  twice  as  often  as  the  ri.i,dn.  The  condition 
may  be  accompanied  by  hematuria,  the  urine  containing  booklets,  less 
commonly  scolices,  and  in  rare  instances  small  cysts  or  fragments  of 
the  cvst-wall. 

Under  the  name  cystic  disease  of  the  kidney,-  polycystic  kidney, 
cystic  degeneration  of  the  kidney,  or  coiglonierate  renal  cysts,  there  has 
been  described  a  peculiar  lesion  manifested  by  the  presence  of  large 
multilocular  cysts  occupying  the  area  of  and  replacing  the  kidney, 
but  frequently  containing  no  discernible  renal  tissue.  In  other  instances 
but   part  of   the   kidney   is  involved.     In  bilateral   cystic  disease  the 


Fig.  332.— Co.ngenital  Cystic  Disease  of  the  Kidney.    (Natural  size.) 

(From  specimen  prr>icntcd  by  Dr.  F^.  E.  Graham.     Original  article  in  ".Archives  of  Pediatrics,"  October,  1899. 

Figures  333,  3?4.  335.  and  33^  ^e  from  the  same  specimen.) 


involved  organs  may  be  so  large  as  to  impede  labor;  Fussell  collected 
II  cases  in  which  it  was  necessary  to  mutilate  the  fetus  in  order  to 
accomplish  delivery.  The  tumors  in  the  adult  may  be  of  enormous 
bulk.  In  Hare's  case  the  left  kidney  weighed  7  kilos.  A  specimen  in 
the  Museum  of  the  Jefferson  Medical  College  is  considerably  larger 
than  a  fetal  head.     The  organ  was  removed  postmortem,  and.  during 

'  Paton.   "Lancet,"  Jan.   21.    1905.  p.    150-     Haynes.   "Annals  of  Surger>-." 
July.    1002.     See  also  p.    190. 

"  ''Howard,  "Cleveland  Jour,  of  Med.."  July.  1900.  Pels.  Munch,  med. 
Woch.,"  Oct.  21.  1902.  p.  174^  and  Oct.  28.  1902.  y.  1799-  Boinet  and  Ray- 
boud  "Rev.  de  Mt-d.."  [an..  "1903.  Pettersson.  'ZieR.  Beitr.."  1903.  vol.  33. 
p.  605.  Morse,  "lour.  Amer.  Med.  Assoc."  Dec.  19.  1903.  p.  1537.  Blackburn. 
•Trans,  of  Path."  Soc.  of  London."  1904.  vol.  55.  p.  203.  Busse.  "  V  irchow  s 
Arch.."  1904.  Bd.   175.  p.  442.  and    "Deut.  med.  \yoch.,"   1904.  No.  4. 


666 


SPECIAL  PATHOLOGY. 


life,  had  given  rise  to  but  slight  inconvenience,  not  at  all  lessening  the 
comfort  or  usefulness  of  a  physician  throughout  a  long  and  active 
professional  career.  Commonlv  the  appearance  suggests  cyst  formation 
beginning  in  the  cortical  portion  of  the  organ,  and,  when  the  subject 
has  survived  to  adult  life,  the  cvsts  may  be  restricted  to  that  structure. 
The  cystic  kidney  is  large,  made  up  of  numerous  cysts,  and  often  shows 
no  recognizable  renal  tissue;  the  fluid  within  the  cyst  is  usually  clear, 
slightly  if  at  all  albuminous,  and  the  urinary  constituents  present  may 
be  no  more  abundant  than  in  cysts  of  other  organs.  Cholesterin  is 
commonly  present,  and  the  cvst  may  contain  a  trace  of  blood  pigment. 


Fig. 


-Kidney,   Congenital  Cystic  Disease;    Laid  Open.     (Same  case  as  Fig.  332.) 


and  not  infrequently  detritus  resulting  from  degenerative  and  necrotic 
processes  in  the  epithelium  of  the  cyst-wall.  Sometimes  the  connective- 
tissue  wall  of  the  cyst  is  not  covered  by  a  recognizable  epithelial  lining. 
In  other  instances  there  is  a  varying  amount  of  epithelium,  which  may 
be  granular  and  necrotic;  and  in  still  other  specimens  low  or  tall  colum- 
nar epithelial  cells  form  the  inner  layer  of  the  cyst-wall.  A  study  of 
these  cysts  in  various  stages  of  evolution  leads  to  the  belief  that  pri- 
marily they  all  possessed  an  epithelial  lining.  The  matrix  between 
them  may  be  fibrous  or  myxomatous,  and  is  not  infrequently  extremely 
vascular. 


niSKASKS   OK   TIIIC    rklXAkY   ORGANS. 


667 


Our  knowledge  of  the  etiology  of  these  congenital  cysts  is  by  no 
means  satisfactory.     Virchow  believed  that  they  were  due  to  a  dilatation 


Fig.  334.— Congenital  Cystic  Disease  of  the  Kidney.     (Tissue  from  near  the  pelvis  uf  the  kidney  shown 

in  Fig.  332.) 
A .  Distended  blood-vessel.     B.  Connective  tissue  similar  to  that  shown  at  C  in  figure  336.      In  many  areas  this 

connective-tissue  matrix  is  made  up  of  multipolar  or  branching  cells,  such  as  occur  in  myxomatous  structures. 

Below  the  blood-vessels  arc  shown  transverse  and  oblique  sections  of  tubules  that  resemble,  to  a  certain  extent, 

sweat-glands.     (J-inch  objective,  i-inch  ocular.) 

of  the  uriniferous  tubules  resulting  from  a  possible  prenatal  inflamma- 
tory condition.     Goodhart  suggested  that  they  were  examples  of  renal 


Fio.  335. — Congenital  Cystic  Disease  of  the  Kii)Nv\ 
Section  of  cvst  showing  columnar  cell-lining  and  contiiined  detritus;    the  latter,  from  .1  sninv  1.1  nm.r  .sections, 
seems  to  be  the  fragmenteil  cvlnpla.sm  of  degenerated  epithelial  cells  cast  off  from  the  cyst-wall.     1  he  section 
is  from  the  kidney  shi.wn  in  figure  332.     (j-inch  objedive.   i  inch  ocular.) 

adenoma,  and  in  this  view  was  supported  by  the  observations  of  Bate- 
man.    As  a  result  of  a  careful  histologic  and  embryologic  study.  Shattock 


668 


SPECIAL  PATHOLOGY. 


came  to  the  conclusion  that  the  condition  depended  upon  the  malde- 
velopment  of  the  mesonephron,  or  Wolffian  body,  fused  with  the  meta- 
nephros,  and  that  the  cvsts  resulted  from  evolutionary  changes  in  the 


W  'i 


Fig.  336.— Congenital  Cystic  Disease  of  the  Kidney.     Part  of  Wall  of  a  Larger  Cyst. 
Section  of  the  kidney  shown  in  figure  332.     A.  Granular  detritus  composed  of  hyaline  material  and  acidophilic 
granules.     B.  Flattened  epithelium.     (Compare  with   columnar  cell-lining  of  smaller  cyst,  tig.  335)     I'- 
Connective  tissue  between  cysts,     (i-iach  objective,  i-inch  ocular.) 

included  mesonephron.  At  the  present  time  the  bias  of  opinion  seenis 
to  be  toward  Shattock's  view;  their  congenital  or  embryonic  origin  is 
generally  conceded. 


DISEASES  OF  THE  BLADDER  AND  URETHRA. 

The  malformations  of  these  organs  have  already  been  referred  to  on 
p.  633.  In  the  female  the  bladder  may  prolapse,  constituting  a  con- 
dition called  vaginal  cystocele.  Frequent  overdistention  and  straining 
during  urination,  associated  with  relaxation  of  the  abdominal  wall, 
may  cause  the  bladder  to  protrude  in  the  median  line  (abdominal 
cystocele).  As  a  result  of  frequent  overdistention,  and  sometimes  from 
other  causes,  the  vesical  wall  is  greatly  thinned  (mural  atrophy). 
The  organ  may  be  small  and  contracted,  but  it  is  probable  that  this 
condition  is  congenital  or  the  result  of  abnormal  irritability,  and  in 
either  case  should  not  be  called  vesical  atrophy. 

In  the  condition  known  as  atony  of  the  bladder  it  is  supposed  that 
the  relaxation  is  due  to  insufficient  tone  in  the  muscle.  In  such  cases 
degenerative  changes  in  the  atrophic  fibers  have  been  described. 

Chronic  congestion  of  the  bladder,  and  also  the  presence  of  Bilharzia 
haematobia,  may  be  attended  by  conspicuous  overdistention  of  the 
veins.  Thrombosis  of  the  pelvic  veins,  cirrhosis  of  the  liver,  and  chronic 
heart  disease  may  also  give  rise  to  venous  dilatation,  sometimes  called 
vesical  hemorrhoids.  Hemorrhage  into  the  bladder  wall  or  submucosa 
may  be  due  to  injury,  sometimes  follows  labor, — in  which  case  it  is  the 
result  of  pressure  of  the  fetal  head  or  instruments, — and  is  also  seen  in 


DISEASES   OF  THE    IKINAkY   ORGANS.  669 

hemorrhagic  diseases.  It  is  possible  that  such  hemorrhages  may  be- 
come infected  and  give  rise  to  extending  necrosis;  such  a  process  may- 
account  for  ruptures  of  the  bhidder  observed  in  the  women  dying  during 
the  puen)crium. 

Hypertrophy  of  the  bladder  may  be  produced  by  any  condition 
causing  slowiv  i)rogressing  obstruction  of  the  urethra  or  vesical  outlet. 
In  such  eases  the  increased  resistance  to  the  outflow  of  urine  induces 
a  gradual  hypertrophy  of  the  muscle  composing  the  bladder  wall,  which, 
when  contracted,  mav  measure  1.5  cm.  The  hypertrophy  is  especially 
marked  in  prostatic  enlargement.  Frequently  the  overgrowth  of  muscle 
is  not  uniform,  or  as  a  result  of  weakening  the  mucosa  pouches  at 
points,  giving  rise  to  a  ribbed  interior. 

Cystitis,  or  inflammation  of  the  bladder,  may  be  acute  or  chronic. 
It  is  possible  to  produce  mtlammation  of  the  mucosa  lining  this  viscus 
by  the  administration  of  cantharides  or  turpentine  and  other  irritants 
excreted  by  the  kidney;  the  most  frequent  cause  is  infection.'  It  is 
possible  that  bacteria  may  reach  the  viscus  from  the  kidney  or  through 
the  vessels  in  the  submucosa;  they  are  most  frequently  introduced, 
however,  from  the  urethra,  and  especially  by  instruments.  The 
microorganisms  usually  found  are  the  colon  bacillus,  staphylococci, 
and  streptococci;  the' typhoid  bacillus  may  also  be  a  cause.  When 
complicating  gonorrhea,  cystitis  is  frequently  due  to  the  gonococcus, 
although  often  the  infection  is  multiple.  Any  condition  (paralysis, 
stricture,  enlarged  prostate)  which  prevents  the  bladder  from  fully 
emptying,  favors  accumulation  of  bacteria  and  their  products,  and 
commonly  leads  to  cystitis.  When  the  inflammation  has  persisted  for 
some  length  of  time.'  the  infection  is  usually  polymicrobic.  A  special 
form  of  cystitis  accompanies  venal  distomatosis.^ 

Morbid  Anatomy} — The  changes  observed  are  those  commonly  oc- 
curring in  inflamed  mucous  membranes.  The  inflammation  may  be 
catarrhal,  suppurative,  hemorrhagic,  gangrenous,  or  pseudomembranous, 
and  the  frequency  with  which  each  form  occurs  corresponds  to  the 
order  in  which  I  have  named  them.  Motz  and  Denis  have  shown  that 
the  subepithelial  infiltration  is  often  extensive  and  the  epithelial  des- 
quamation less  abundant  than  we  had  previously  believed.  Even  in 
catarrhal  processes  marked  dilatation  of  the  vessels,  extensive  leuko- 
cyte migration,  and  sometimes  slight  escape  of  red  blood-cells  occur. 
Such  changes  account  for  the  intense  redness  of  the  affected  mucous 
membrane.  In  the  suppurative  cases  minute  abscesses  may  be  formed 
in  the  submucosa,  and  the  number  of  leukocytes  observed  in  the  urine 
is  much  greater  than  in  any  other  form  of  cystitis.    According  to  Parodi, 

'  Experimental  and  laboratory'  studies  of  the  flora  found  in  cystitis  have 
t>een  extensive.  The  important  observations  will  be  found  in,  or  may  be  traced 
from,  the  following  references:  Hofmann.  'Centralbl.  f.  Grenzgebiet.  der  Med.  u. 
Chir."  vol.  vii,  No.  20.  Baisch,  "Beitr.  z.  Geburts.  u.  G\nak.,"  1904.  Bd.  vni. 
H.  2.  Breton,  "Gaz.  des  Hop.,"  1902,  vol.  5,  p.  533-  Paton,  "Jour,  of  Path, 
and  Bact.."  Sept..  1Q02.  p.  280.  Stokes,  "lour.  Amer.  Med.  Assoc,"  Sept.  27. 
1902.  p.  733-  Mellin.  'Jahrb.  f.  Kinderheilk.,"  1903,  vol.  Iviii,  p.  40.  Zclenski, 
"Wicn.  klin.  Woch.,"  Feb.  4.   1904.  P-   123. 

'Goebel,   "Deut.   Zeit.   f.  Chir.,"    Bd.   66,   U.   3   and   4.     Milton,    '•Lancet. 
March  28,  1903.  p.  866.     See  also  p.  193.  . 

^  Motz  and  Denis.  "Annals  des  Mai.  Gen.  Unnaires."  1903.  vol.  xxi.  No  .12- 
Parodi.  "Arch,  per  le  Sci.  Med.."  1904.  vol.  xxviii.  fasc.  i.  Hofmann.  "Wien. 
klin.  Rundsch.."  1904.  No.  49.     Dean.  "Practitioner,"  June,  1904,  p.  907. 


670  SPECIAL  PATHOLOGY. 

the  so-called  cystic  inflammation  of  the  bladder  results  from  degenerative 
changes  in  the  inflamed  mucosa;  the  resulting  miliary  cysts  are  most 
abundant  in  the  posterior  and  superior  portions  of  the  organ.  In  gan- 
grenous cystitis  large  areas  of  the  mucosa  undergo  necrosis,  the  tissue 
death  frequently  extending  into  the  muscular  layer  and  sometimes 
perforating.  It  is  usually  an  evidence  of  intense  infection,  and  com- 
monly occurs  in  the  debilitated.  The  so-called  pseudomembranous 
cystitis  is  rarely  attended  by  the  production  of  a  false  membrane  com- 
parable to  that  seen  on  other  mucosae,  although  the  macroscopic  re- 
semblance ma}'  be  strong.  Dean's  examination  of  the  specimen  from 
his  patient  corroborated  Adami's  view  that  the  disease  depends  upon 
a  superficial  necrosis  of  the  mucosa.  In  the  chronic  inflammations  of 
the  bladder  there  is  often  notable  thickening  of  the  mucosa  and  sub- 
mucosa,  and  in  some  cases  a  perceptible  increase  in  the  muscle  layer. 
The  studies  of  Tyler,  Brown,  and  also  Stokes,  seem  to  disprove  the 
prevailing  belief  that  the  urine  is  alkaline  in  cystitis.  The  percentage 
of  cases  in  which  normal  acidity  disappears  is  small.  The  vesical 
changes  accompanying  venal  distomatosis  will  be  found  described 
on  page  194.  Cystitis  is  not  infrequently  followed  by  inflammation 
of  the  ureter,  and  may  precede  or  follow  prostatitis.  Inflammation 
around  the  bladder  (pericystitis)  may  be  secondary  to  intracystic 
processes,  or  results  from  inflammatory  conditions  arising  in  contiguous 
structures. 

Vesical  calculi  may  be  composed  of  uric  acid  or  its  salts  and  the 
salts  of  calcium,  especially  the  carbonates,  phosphates,  and  oxalates. 
The  concretions  vary  in  size  from  small  particles,  so-called  vesical 
sand,  to  masses  weighing  100  gm.  or  more.  They  are  particularly 
prone  to  form  around  foreign  bodies.  It  is  probable  that  the  formation  of 
concretions  within  the  bladder  is  favored,  if  not  caused,  by  the  presence  of 
bacteria.  It  is  well  known  that  in  chronic  vesical  inflammation  phosphatic 
calculi  frequently  occur,  and  are  usually  attributed  to  changes  in  the  reac- 
tion of  the  urine  induced  by  the  bacteria.  Often  the  stones  are  multiple, 
and  by  attrition  wear  smooth  surfaces  (facets)  at  the  points  of  contact. 
The  nuclei  of  most  calculi  consist  of  a  colloid  containing  uric  acid. 
When  the  stone  is  composed  entirely  of  this  substance,  it  is  yellow 
or  reddish-brown  and  the  surface  irregular.  On  section  stratification 
is  usually  evident,  particularly  in  the  larger  stones.  When  composed 
of  calcium  oxalate  the  calculus  is  hard,  sometimes  spiculated,  and  the 
surface  formed  of  small  bosses  {mulberry  calctdus).  The  phosphatic 
calculi  are  composed  of  triple  phosphates  and  usually  contain  urate  of 
ammonium  and  calcium  carbonate.  Occasionallv  the  stone  consists  of 
calcium  carbonate  alone.  Cystin,  xanthin,  and  cholesterin  calculi  are 
rare;  a  few  cases  of  indigo  calculus  have  been  reported.  Vesical  lithiasis 
is  commonly  attended  by  cystitis,  which  in  some  cases  is  marked. 
Hematuria  is  frequently  present. 

Tuberculosis  of  the  bladder  may  be  a  part  of  a  wide-spread  genito- 
urinary lesion  involving  the  kidney,  ureter,  bladder,  prostate,  seminal 
vesicles,  spermatic  duct,  epididymis,  and  testicle.  The  infection  may 
occur  from  the  blood,  by  lymphatic  extension,  or  from  contiguous 
lesion  in  the  prostate  or  seminal  vesicles,  or  other  adjacent  tissues. 
In  general  miliary  tuberculosis,  tubercles  may  be  observed  in  the  sub- 
mucosa  of  the  bladder;    they  are  rarely  conspicuous  or  abundant.     The 


Pl.ATH    X. 


E     F     E 


TUBERCULOSIS   OF   THE   BLADDER 

Drawing  made  from  fresh  specimen 

One-half  natural  size 

Drawn  bv  Miss  E.  G.  Harding 


LABORATORIES  OF  THE  JEFFERSON  MEDICAL  COLLEGE  HOSPITAL 


A.— Centre  of  large  ulcer.    At  the  end  of  the  line  is  a  distinct  furrow,  to  which  was 

attached  a  recent  slough. 
B.— Similar  ulcer,  but  more  recent. 

C— More  recent  ulcer  almost  ready  to  become  cotiflueiit  with  the  large  ulcer. 
D.D.D.-Miliary  tubercles.      These  at   first  glance  resembled  ulcers,  but  close  inspection 
showed  that  they  had  not  as   yet  broken  down.      Many  of  these  are  «t»-en.  par- 
ticularly at  the  Viase  of  the  bladder. 
E.E.E.E.— The  point  from  which  was  excised  the  trigone  prostate  and  urethra. 

F.F.F.— Points  showing  the  patchy  inflammation  of  the  mucosa,  which  accomprtim  -  m   •  i 
culosis  of  the  bladder. 


DISliASES  OK  Tin-    l-klNAUY   ORGAN'S.  67  I 

most  tro(iiK'.m  nuinifestation  of  vesical  tuberculosis  is  the  ulcerative 
form,  which  is  rarely,  if  ever,  primary.  The  ulcers  may  be  solitary 
or  multiple;  commonly  there  is  a  sin«,'le  lar^e  ulcer,  near  which  are 
grouped  numerous  smaller  ones  which  extend  by  coalescence.  The 
tloor  of  the  ulcer  is  shaj^i^y,  dirty  yellow  in  color,  and  often  undulated; 
as  a  rule,  the  muscular  layer  of  the  bladder  escapes,  althoui,di  Senn 
observes  that  the  wall  is  sometimes  perforated.  The  edj,'cs  of  the  ulcer  are 
usually  elevated,  slightly  undermined,  and  but  little  indurated.  Com- 
monlv  the  entire  vesical  mucosa  is  the  seat  of  patchy  hyperemia,  which 
is  particularly  marked  near  the  margins  of.  the  ulcer;  this  in  part  ac- 
counts for  the  accompanying  hematuria.  As  a  result  of  mixed  infection 
the  coincident  cvstitis  is  often  marked,  and  erosions  of  the  mucosa  are 
frequentlv  present.  Bryson  has  noted  the  occurrence  of  .submucous 
rhexis  giving  rise  to  punctate  hemorrhages  which  are  ])articularly  almnd- 
ant  in  the  zone  nearest  the  ulcer.  Small  sloughs  coming  from  the  lesion 
and  tubercle  bacilli  can  usually  be  demonstrated  in  the  urine. 

The  microscopic  examination  of  such  ulcers  renders  it  evident  that 
the  extension  is  not  wholly  due  to  the  presence  of  tubercle  bacilli. 
Characteristic  tubercles  are  rarely  abundant,  and  are  more  conspicuous 
near  the  margins  of  the  ulcer  than  in  the  floor.  Necrosis  and  disinte- 
gration rapidly  invade  the  developing  tubercle  and  promptly  convert 
it  into  a  small  ulcer,  which,  if  seated  near  the  larger  lesion,  quickly 
becomes  confluent  with  the  latter.  Many  of  the  smaller  blood-vessels 
are  thrombosed,  and  I  have  no  doubt  this  is  a  determining  factor  in 
the  extension  of  the  necrosis.  Tubercle  bacilli  are  not  commonly 
abundant  in  the  lesion. 

Tumors  of  the  bladder^  are  not  of  frequent  occurrence;  Gurtl,  in  an 
analvsis  of  16.6S7  tumors  of  all  kinds,  found  66  vesical  neoplasms. 
Thev  are  twice  as  frequent  in  men  as  in  women.  The  secondary  tumors 
of  the  organ  are  the  result  of  extension  from  some  contiguous  tissue, 
usuallv  the  prostate;  metastasis  to  the  bladder  is  rare.  The  most  com 
mon  of  these  neoplasms  is  the  papilloma,  called  by  Rokitansky  villous 
cancer,  but  shown  by  Virchow  to  be  i)rimarily  nonmalignant.  Tlie 
surface  of  such  neoplasms  is  composed  of  long  slender  fimbriae  (papil- 
loma fimbriatum)  which,  when  the  bladder  is  empty,  may  be  caught 
in  the  urethral  orifice  and,  by  subsequent  distention  of  the  organ, 
pulled  off,  in  this  way  wounding  the  slender  vessels  in  the  connective- 
tissue  core  of  the  papilla  and  producing  hemorrhage,  which  may  be 
fatal.  Usually  such  masses  are  small,  although  papilloma  of  this  type 
mav  involve  the  entire  vesical  mucosa.  They  are  sometimes  associated 
with  the  presence  of  calculi,  to  which  they  may  be  due.  Occasionally 
such  tumors  become  cancerous,  and  in  that  way  offer  some  justification 
for  the  term  villous  carcinoma  of  the  bladder.  In  such  cases  the  wall 
of  the  organ  is  invaded  by  the  new  growth,  which  may  also  extend 
into  contiguous  tissues.  As  the  papilloma  commonly  arises  in  the  area 
of  the  trigone,  the  secondary  cancers  also  occupy  this  region.  Both 
the  papilloma  sind  carcinoma  are  usually  accompanied  by  catarrhal 
cystitis,  and  it  is  possible  that  they  may  follow  long-continued  irritation; 

'  Lendorf.  "Hospitalstende,"  Copenhagen.  Ixvii.  No.  30.  Freycr.  "Lancet." 
Ian.  24.  1903.  p.  215.  Spooner.  "Post-Graduate,"  Oct..  1903.  p.  859.  Grclin- 
ski.  •Zentralbl.  f.  Chir.."  Oct.  20.  iqo4-  Lockwood.  -Lancet,"  June  11.  1904. 
p.  1633.     Wilder.  "Amer.  Jour,  of  Med.  Sci."  Jan..  1905. 


672  SPECIAL  PATHOLOGY. 

similar  growths  are  produced  by  Bilharzia  haematobia  infection. 
Scirrhous  carcinoma  and  encephaloid  carcinoma  of  the  bladder  occur; 
they  are,  however,  exceedingly  rare.  Fibroma,  myxoma,  and  myoma 
are  infrequent  tumors  of  the  bladder.  Primary  sarcoma  of  the  bladder 
has  been  reported,  but  is  infrequent;  of  the  eighty-eight  vesical  neo- 
plasms studied  bv  Albarran,  only  three  were  sarcomata;  they  are  always 
sessile  and  arise  in  the  connective  tissue  of  the  bladder-wall. 

The  most  frequent  disease  of  the  urethra  is  inflammation  (urethritis), 
which  may  be  acute  or  chronic  and  is  usually  purulent.  A  specific 
inflammation  of  the  urethra  due  to  gonococcus  is  called  gonorrhea.  (See  p . 
107.)  After  a  brief  period  of  incubation  (usually  a  few  days)  the  mucosa 
of  the  urethra  is  reddened,  rapidly  followed  by  a  discharge  which  at 
first  is  catarrhal  in  type,  but  soon  contains  a  sufficient  number  of  poly- 
miorphonuclear  leukocytes  to  justify  the  name  purulent.  The  epithe- 
lium desquamates  rapidly,  at  points  exposing  the  membrana  propria 
and  giving  rise  to  the  intense  irritation  particularly  during  urination. 
In  mild  cases  the  changes  of  the  submucosa  are  not  marked;  when  the 
infection  is  severe  or  has  persisted  for  some  time,  the  polymorphonuclear 
leukocytes  infiltrate  the  connective  tissue  and  may  even  collect  in 
sufficient  numbers  to  give  rise  to  small  abscesses.  Usually  the  inflam- 
mation stops  short  of  actual  suppuration  in  the  submucosa.  The  in- 
tense swelling  of  the  earlier  stages  may  constitute  an  obstruction  to 
the  flow  of  urine,  and  is,  in  part  at  least,  the  cause  of  the  so-called 
spasmodic  stricture  of  this  stage.  Often,  after  a  period  of  acute  muco- 
purulent catarrh,  a  chronic  urethral  discharge  continues,  usually  asso- 
ciated with  the  development  of  strictures.  The  latter  are  due  to  the 
production  of  fibrous  tissue  in  the  submucosa,  followed  by  contraction. 
They  give  rise  to  irregularities  and  pockets  in  which  the  infection  per- 
sists, particularly  in  the  posterior  portion  of  the  urethra  (posterior 
urethritis).  The  inflammation  may  extend  to  the  seminal  sacs,  pros- 
tate, and  epididymis;  the  bladder  is  frequently  involved.  In  chronic 
cases,  particularly  when  strictures  are  present,  the  ureter  and  pelvis 
of  the  kidney  may  become  infected;  occasionally  the  organism  enters 
the  blood.     (See  Gonococcemia,  p.  109.) 

Acute  catarrhal  urethritis,  also  called  simple  urethritis,  or  non- 
specific urethritis,  may  result  from  chemic  irritation,  or  be  due  to 
infection  by  bacteria  other  than  the  gonococcus.  The  staphylococci 
and  sometimes  virulent  colon  bacilli  induce  the  inflammation.  Usually 
this  type  of  urethritis  is  less  intense  than  that  due  to  the  gonococcus. 
Other  types  of  mucous  membrane  inflammation  occasionally  involve 
the  urethra,  but  rarely  give  rise  to  conspicuous  lesions. 


CHAPTER    X. 
ALIMENTARY    CANAL. 

The  alimentary  canal  consists  essentially  of  a  tube  extending  from 
the  lips  of  the  anus,  with  dilatation  at  various  points  for  the  temporary 
retention  of  food  during  the  processes  of  digestion.  In  the  different 
parts  of  the  canal  are  glands,  the  secretions  of  which  promote  digestion. 
The  largest  of  these  glands  are  anatomically  distinct  from  the  alimentary 
tube,  but  physiologically  they  are  as  much  a  part  of  the  canal  as  are  the 
glands  in  the  mucosa;  thus,  the  essential  and  important  secretions  of 
the  mouth  are  supplied  by  the  salivary  glands,  all  of  which  lie  without 
the  mucosa  of  the  oral  cavity;  the  secretion  of  the  stomach  is  from 
glands  in  the  lining  membrane;  the  mucosa  of  the  bowel  yields  the 
siucus  oitcriciis,  a  product  of  the  intestinal  glands;  the  most  impor- 
tant secretions,  utilized  in  intestinal  digestion,  come  from  the  pancreas 
and  liver.  As  each  special  part  of  the  alimentary  canal  deals  with 
a  material  the  chemistry  of  which  differs  from  the  contents  in  other 
regions,  and  as  there  are  important  modifications  in  the  anatomy  of 
each  division,  the  diseases  of  the  various  areas  also  differ. 

For  convenience  in  study  the  alimentary  canal  is  divided  into  the 
mouth  (including  the  pharynx),  esophagus,  stomach,  small  intestine, 
and  large  intestine. 

THE   MOUTH. 

The  mucous  membrane  of  the  mouth  consists  of  a  thick  layer  of 
stratified  epithelium  resting  upon  a  loose  and  elastic  basement  mem- 
brane, under  which  is  a  most  abundant  submucosa,  containing  a  large 
quantitv  of  loose  connective  tissue ;  this  is  necessary  in  order  to  enable 
the  mucous  membrane  to  adapt  itself  to  the  sudden  changes  in  volume 
to  which  the  mouth  is  constantly  subjected. 

Malformations  of  the  Mouth.' — The  mouth  is  developed  from  the 
branchial  arches,  failure  in  the  fusion  of  which  results  in  the  formation 
of  clefts.  When  the  failure  of  union  is  restricted  entirely  to  the  upper 
lip  and  invades  the  soft  parts  only,  the  condition  is  properly  termed 
harelip  ;  manv  writers  include  with  this  condition  fissure  of  the  superior 
maxilla  immediately  under  the  labial  defect.  The  fissure  in  the  lip 
is  usually  directly  below  the  nasal  orifice,  and  in  about  ninety  per 
cent,  of  the  cases  is  restricted  to  one  side.  When  both  sides  are  in- 
volved, the  condition  is  called  double  harelip.  As  development  of  the 
alveolar  process  and  palate  is  intimately  connected  with  the  union  of 
the  soft  parts  forming  the  upper  lip,  it  is  not  infrequent,  when  defects 
occur  in  the  latter,  for  them  to  extend  backward  and  to  involve  the 

'See  Maclennan,   "Brit.  Med.  Jour.."  Dec.    19,   190.^.  p.   1580.     Also  Salzer. 
"Zeitsch.   f.   Heilk,"   Sept..    1902.       Graetzer.   "Vademecum  der    Kindeq^raxis." 
1903,  p.  27.     Owen,  "Cleft  Palate  and  Harelip,"  London.  1904. 
44  673 


674  SPECIAL  PATHOLOGY. 

osseous  structure  that  forms  the  roof  of  the  mouth.  Such  a  condition 
is  called  cleft  palate.  The  fissure  may  be  limited  to  a  small  niche  between 
the  incisors  and  canine  teeth,  or  it  may  extend  entirely  through  the 
hard  palate,  converting  the  nasal  and  oral  spaces  into  one  cavity;  occa- 
sionallv,  the  failure  of  union  extends  still  further — a  cleft  palate  becomes 
cleft  face.  A  median  fissure  situated  in  the  lower  lip,  and  comparable 
in  a  certain  way  to  harelip,  is  occasionally  observed,  although  state- 
ments to  the  contrary  are  often  made. 

More  or  less  faulty  development  of  the  arch  forming  the  inferior 
maxilla  may  result  in  a  cleft  at  the  chin  or  in  entire  absence  of  the  bone 
— a  condition  known  as  agnathia.  In  the  four  cases  of  agnathia  studied 
by  Kuse^  cartilaginous  structures,  representing  rudimentary  jaws,  were 
present.  This  malformation  is  likely  to  be  associated  with  cyclopia. 
Closure  of  the  fissure  that  enters  into  the  formation  of  the  mouth,  when 
more  marked  than  usual,  gives  rise  to  microstoma.  Failure  to  close 
to  the  usual  degree  leads  to  the  formation  of  an  unusually  large  mouth, 
called  macrostoma.  Arrests  in  development  may  give  rise  to  fistulse, 
through  which  the  mouth  or  pharynx  communicates  with  the  exter- 
nal surface  by  some  abnormal  route.  Occasionally,  passages  which 
were  originallv  complete  fistulae  close  at  one  or  both  ends,  thereby 
giving  rise  to  "incomplete  fistulas  or  to  closed  cavities  in  which  cystic 
dilatation  may  occur.  As  these  abnormal  tracts  usually  arise  from 
faulty  union  of  the  branchial  arches,  they  are  called  branchial  fistulae, 
or  when  distinct  cavities  are  present,  branchial  cysts.-  The  wall  may 
contain  Ivmphoid  tissue,  and  occasionally  dilated  lymph-spaces,  which 
may  become  lymphangiomatous ;  sometimes  hemangiomata  are  present. 
The  complete  fistulas  ordinarily  extend  from  Rosenmuller's  fossa  behind 
the  tonsil,  under  the  digastric  muscle,  and  open  in  the  neighborhood 
of  the  sternocleidomastoid.  The  track  of  such  fistulse,  or  the  cyst  wall, 
can  constitute  the  epithehal  structure  from  which  cancer  (branchiogenic 
carcinoma)  arises.  The  uvula  may  be  bifid  or  fenestrated;  Mullen' 
has  recorded  a  supernumerary  uvula.  Malformations  of  the  tongue* 
are  not  frequent.  The  organ  may  be  bifid  or  cleft,  and  occasionally 
the  clefts  give  rise  to  a  number  of  lobes — the  lobulated  tongue.  Lingual 
adhesions  to  the  Hp,  floor  of  the  mouth,  gums,  and  palate  are  sometimes 
observed.  The  condition  called  tongue-tie  or  ankyloglossia  is  usually 
due  to  an  abnormally  short  frenum,  although  essentially  the  same  result 
may  be  due  to  adhesions.  An  abnormally  large  tongue,  macroglossia, 
may  be  produced  by  hyperplasia  of  the  connective  tissue  of  the  organ, 
but  it  is  usually  a  manifestation  of  lymphangiectasis.  Macroglossia 
neurofibromatosa  has  been  described.  Similar  lymphangiectasis  some- 
times affects  the  lip,  in  which  location  it  is  called  macrocheilia.  Eisen- 
drath^  reports  a  macrocheilia  due  to  adenomatous  enlargement  of  the 
glands  of  the  labial  mucosa. 

1  "Miinch.  med.  Woch.,"  May  28,  1901. 

2  See  Coplin  and  Brick.  "  Phila.  Med.  Jour.,"  April  23,  1902.  Germond, 
These  de  Paris,  1902.  Konig,  "Arch.  f.  klin.  Chir.,"  1903.  Bd.  Ixx.  p.  1008. 
Hammar,  'Ziegler's  Beitr.,"  1904,  Bd.  36,  p.  506.  Brunet,  "Volkmann's  Samm- 
lung  klin.  Vortrage,"  xii,  Seri.  30,  1904. 

'  "Laryngoscope,"  May,  1902. 

*  Bywater,  "Brit.  Med.  Jour.,"  Oct.  12,  1901.  Abbott  and  Shattock,  "Trans. 
Path.  Soc.  of  London,"  1903,  vol.  54,  p.  231.  Rosenak  and  Feldman,  "Centralbl. 
f.  allg.  Path.  u.  path.  Anat.."  Jan.  31,  1905,  p.  57. 

'  "Annals  of  Surgery,"  Sept.,  1904,  p.  320. 


AI.IMKNTAKY    CANAL.  675 

Inflammation  of  the  month  is  known  as  stomatitis,'  and  may  be 
catarrhal,  pseudomeml^ranous,  gangrenous,  lieinorrhagic,  or  suppura- 
tive. 

Follicular  stomatitis  is  an  inflammatory  process  in  which  the  follicles 
or  mucous  glands  are  the  seat  of  the  most  active  inflammation ,  with 
the  develoi>ment  of  vesicles,  and  with  closure,  and  finally  distention, 
of  the  ducts,  which  may  terminate  in  coagulation  necrosis  of  the  upper 
layer,  giving  rise  to  small  ulcers. 

Ulcerative  stomatitis,-  also  known  as  putrid  sore  month,  occurs  in 
weak,  debilitated  children,  and  occasionally  in  adults;  improper  feeding 
and  failure  to  keep  the  mouth  clean  may  cause  it;  chronic  poisoning, 
such  as  lead,  mercury,  or  phosphorus,  may  induce  this  condition.  It 
occasionally  shows  a  disposition  to  be  contagious,  and  this  suggests 
the  possibility  of  its  being  due  to  a  specific  germ,  which,  however,  has 
not  been  demonstrated,  although  successful  inoculation  on  the  healthy 
gum  has  been  practised.  Some  cases  of  ulcerative  stomatitis'  are  due 
to  the  diphtheria  bacillus ;  in  rare  instances  the  process  may  be  a  mani- 
festation of  tuberculosis  or  arise  as  a  complication  of  lingual  or  even 
pulmonary  infection  by  the  tubercle  bacillus. 

This  type  of  oral  lesion  usually  begins  as  an  ulcerative  process 
involving  the  gum,  and  is  therefore  sometimes  termed  phagedenic 
gingivitis.  It  spreads  superficially  along  the  gingival  margin,  and  gives 
rise  to  loosening  of  the  teeth,  which  may  drop  out.  The  ulcers  rarely 
involve  the  mucosa  of  the  tongue  and  cheek;  the  base  of  the  ulcer 
often  contains  a  grayish-white  slough;  the  accompanying  catarrhal 
inflammation,  and  decomposition  of  the  inflammatory  products  and 
necrotic  tissue,  give  rise  to  an  exceedingly  olYensive,  sickening  stench, 
which  has  led  to  the  designation,  putrid  or  fetid  stomatitis. 

Foot-and-mouth  disease*  is  evidently  the  result  of  infection,  although 
its  exact  character  has  not  as  yet  been  determined.  The  disease  is 
most  frequent  in  ruminants,  particularly  cows,  but  abundant  evidence 
has  been  accumulated  to  establish  the  fact  that  it  is  communicable 
to  man.  The  disease  is  characterized  by  the  occurrence  of  vesicles  on 
the  buccal  mucosa,  and,  although  less  commonly,  on  the  entire  oral 
mucosa.  The  inflammation  begins  by  evident  hyperemia  and  consid- 
erable thickening  of  the  corium ;  vesicles  form  in  the  Malpighian  layer, 
eventually  displacing  the  overlying  corneum,  which  ruptures  and  ex- 
foliates, giving  rise  to  an  ulcer.  These  ulcers  may  become  confluent 
and  attain  a  diameter  of  one  or  two  centimeters.  Many  of  them  consist 
of  simple  erosions  or  of  exfoliations  secondary  to  eruption  of  the  vesicle, 
therefore  not  meriting  the  term  ulcer.  During  the  progress  of  the 
affection  in  the  mouth  there  is  usually  more  or  less  fever,  and  in  the 
lower  animals  a  similar  enjf»tion  appears  on  the  feet. 

Parasitic  or  mycotic  stomatitis,  or  thrush,  is  an  infection  occurring 
most  frequently  in  nursing  children,  and  is  due  to  the  thrush  fungus. 
(See  p.  165.)  This  fungus  does  not  seem  to  attack  the  normal  mucous 
membrane,  but  becomes  engrafted  upon  a  mucosa  the  surface  of  which 

'  For  morbid  anatomy,  morbid  histolog>-.  etc.,  see  Inflammations  of  Mucous 
Membranes,  p.  546. 

'  .Also  see  Vincent's  anj^na.  p.  17.3. 

'  Munro,  "Boston  Med.  and  Surg.  Jour."  Dec.  13.  1000. 

*  Brush.  "Jour.  .Amer.  Med.  Assoc.."  June  20,  1903.  p.  1701. 


676  SPECIAL   PATHOLOGY. 

is  eroded  or  irritated  by  improper  feeding  or  other  causes;  the  disease 
is  occasionally  seen  in  adults  after  or  during  acute  febrile  processes 
or  chronic  diseases.  The  parasite  pullulates  in  the  interstices  of  the 
epithelium  and  forms  a  membrane,  usually  superficial,  but  which  some- 
times extends  to  the  basement  membrane,  and,  by  mixed  infection,  may 
lead  to  ulceration.  The  membranous  spots  vary  in  size;  at  first  the 
diameter  rarely  exceeds  four  or  five  inillimeters.  The  erosion  is  commonly 
white  or  creamy  white,  not  easily  detached,  and,  on  microscopic  exami- 
nation, contains,  in  addition  to  the  specific  fungus,  many  extraneous 
organisms.  The  disease  usually  begins  on  the  tongue,  but  may  arise  pri- 
marily on,  or  spread  to,  the  cheek,  and  thence  to  the  tonsils,  palate, 
phar3mx,  and  esophagus;  it  differs  from  the  preceding  forms  of  stomatitis 
in  the  presence  of  the  germ  and  in  the  fact  that  it  is  generally  associated 
with  marked  dr^mess  of  the  mouth,  in  contradistinction  to  the  ptyalism 
that  commonly  accompanies  other  forms. 

Aphthous  stomatitis  is  a  disease  of  infancy  or  childhood,  but  is  oc- 
casionally observed  m  adults.  The  clinical  history,  the  distribution, 
and,  to  a  certain  extent,  the  lesions  indicate  a  possibly  infectious  cause. 
On  the  mucous  membrane  small  papules  appear;  these  are  sometimes 
converted  into  vesicles,  and  later  undergo  a  superficial  necrosis,  giving 
rise  to  what  is  sometimes  incorrectly  termed  an  ulcer.  True  ulceration 
— that  is,  involvement  of  the  connective  tissue— is  rare.  The  white, 
yellowish-white,  or  grayish  erosions  often  present  slightly  elevated  edges, 
which  may  be  hyperemic.  There  is  usually  more  or  less  infiltration  of 
the  adjacent  connective  tissue,  which  does  not,  however,  undergo  necrosis 
except  in  very  rare  instances.  The  erosions  are  commonly  located  on 
the  inner  surface  of  the  lip,  although  any  part  of  the  mouth  may  be 
involved. 

Gangrenous  stomatitis^  (also  known  as  cancruni  oris  and  noma) 
usually  begins  as  a  gangrenous  process  attacking  the  gums  or  cheeks, 
attended  by  sloughing  in  the  structures  involved.  The  soft  parts  and 
bones  may  become  gangrenous  and  slough  to  such  an  extent  that  the 
greater  part  of  the  face  may  be  destroyed  by  the  phagedenic  process. 
The  disease  usually  follows  some  of  the  acute  infectious  processes  in 
children;  Osier  states  that  fifty  per  cent,  of  the  cases  follow  measles. 
Girls  suffer  more  frequently  than  boys.  The  affection  is  most  frequent 
between  the  second  and  the  fifth  year,  although  the  cases  the  author 
has  seen  have  been  in  older  children — from  seven  to  nine  3^ears  old. 
In  the  beginning  the  affected  tissues  are  hard  and  edematous,  but 
rapidly  become  softer  and  fetid.  When  involving  the  jaw,  the  teeth 
loosen  and  fall  out.  In  many  instances  a  complicating  bronchopneu- 
monia, the  lesions  of  which  may  become  gangrenous,  terminates  the 
case;  death  may  also  result  from  septicemic  or  toxemic  complications, 
and  in  rare  cases  the  fatal  issue  is  hastened  by  depleting  hemorrhages. 
The  infrequency  of  bleeding  is  attributable  to  the  extensive  thrombosis 
of  the  vessels  in  the  affected  area.     Trambusti  has  shown  that  the  lesion 

^  Ness,  "Edinburgh  Med.  Jour.,"  June,  1899.  Strauwen,  "Gaz.  Heb.  de 
Med.  et  de  Chir.,"  Aug.  22,  1901.  Sailer,  "Proc.  Phila.  Co.  Med.  Soc,"  Nov., 
1901,  p.  301.  Trambusti,  "  R.  Accad.  med.  di  Palermo,"  Dec.  21,  1901,  also 
"II  Policlin.,"  Jan.,  1902.  Fischer,  "Amer.  Jour,  of  Med.  Sci.,"  April,  1902. 
Korsch,  "  Bolnit.  Gaz.  Bot.,"  1902,  No.  24.  Oberwarth,  "  Deut.  med.  Woch.," 
April  23,  1903.  Hofmann  and  Kuster,  "Berl.  klin.  Woch.,"  Oct.  24,  1904.  See 
also  Noma,  and  bibliography,  p.  256. 


.\i.imi:nt.\rv  canal. 


677 


is  a  progressing  necrosis.  All  attempts  to  estalilish  a  specific  etiology 
for  noma  have  been  improductive.  The  organisms  described  by  Lin- 
gard,  Trambusti,  Perthes,  von  Ranke,  and  others,  and  also  pyococci, 
typhoid  baiilhis.  diplitlicria  bacillus,  and  other  bacteria  occur. 

Gonorrheal  stomatitis'  sometimes  occurs  in  adults  and  has  been 
observed  in  the  newborn  and  nurslings.  It  is  manifested  by  a  catarrhal 
or  mucopunilent  inHammation  involving  particularly  the  mucosa  of 
the  gums  and  check;  sometimes  a  dirty  gray  coating  resembling  pseudo- 
membrane  is  formed.  Sujierlicial  erosions  and  even  deeper  ulceration 
are  occasional Iv  observed. 


Fic.  337. — Loss  OF  TissuK  Due  to  N'oma.     (Dr.  Nlixirc's  cu.se  of  recovery  and  .subsequent  operation  reported 

in  the  "  Intercolonial  Medical  Journal."  of  .\ustralasia.  vol.  iii,  .\o.  10.) 

The  destruction  of  the  soft  parts  and  the  necrotic  ma.ss  of  Ixine  with  an  effort  at  marginal  healing  are  well  shown. 

Cicatrization  is  giving  rl.^-  to  ectropion.     (Patient  aged  seven  ye.irs;   the  process  followed  typhoid  fever.) 

Pseudomembranous  stomatitis  is  usually  due  to  the  diphtheria 
bacillus,  but  occasionally  results  from  infection  by  streptococci,  staphylo- 
cocci, the  spirillum  of  Vincent,  and  pneumococci;  it  is  a  recognized 
complication  of  pneumonia  and  diphtheria. - 

Tuberculous  stomatitis  is  almost  invariably  secondary  to  infection 
of  the  air-passages,  particularly  the  lungs.     In  the  case   reported  by 

'  Jtirgens,  "Berl.  klin.  W<;)ch.,"  June  13,  1904. 
'  Frazier,  "Med.  Times."  Dec,  1903. 


678  SPECIAL   PATHOLOGY. 

Walter  the  infection  began  in  the  socket  of  an  extracted  tooth.  Per- 
foration of  the  palate  may  be  due  to  tuberculous  ulceration  of  the 
vault  of  the  mouth,  but  is  usually  of  syphilitic  origin. 

Syphilis  of  the  mouth, ^  in  the  tertiary  stage  of  the  disease,  usually 
attacks  the  tongue.  The  initial  lesion  affects  the  lip  more  frequently 
than  any  other  part  of  the  oral  cavity.  Of  the  207  extragenital  chan- 
cres collected  by  Neumann,  106  were  on  the  lips.^  The  histology  of  the 
lesion  in  this  location  is  essentially  the  same  as  in  chancres  occurring 
elsewhere.  Mucous  patches  (see  p.  179)  may  occur  on  almost  any  part 
of  the  buccal  mucosa,  but  are  commonest  on  the  lips  and  palate.  In 
the  tertiary  stage  of  syphilis  gumma  involves  the  mucosa  or  submucosa 
or  may  occur  in  the  deeper  tissues,  particularly  of  the  tongue.  The 
ulcerations  of  the  mouth  accompanying  tertiary  syphilis  may  be  differ- 
entiated from  tuberculosis  by  the  demonstration  of  tubercle  bacilli  and 
the  presence  of  histologic  tubercles  in  the  lesion. 

Oral  sepsis"  should  include  the  various  inflammatory  conditions 
affecting  the  mouth  and  attended  by  manifest  infection.  Hunter 
believes  that,  in  addition  to  the  purely  local  influence  exerted  by 
septic  processes  involving  the  oral  mucosa  and  gums  (gingivitis), 
important  secondary  manifestations  are  not  infrequent.  Alveolar 
abscess,  periosteitis,  suppurative  inflammations  of  the  antrum  and 
nasal  sinuses,  tonsils,  pharynx,  and  middle  ear,  may  be  secondary 
to  lesions  primary  in  the  buccal  mucosa.  Local  infection  traveling  by 
the  lymphatics  may  implicate  the  submaxillary  and  anterior  cervical 
lymph-nodes.  Inflammations  of  the  gastro-intestinal  mucosa  may  be 
caused  by  pyogenic  organisms  which  are  primarily  colonized  in  the 
mouth.  Hematogenous  infection,  manifested  by  pleurisy  and  other 
forms  of  serositis,  and  even  ulcerative  endocarditis,  may  have  a  similar 
origin.  Hunter's  contention  that  pernicious  anemia  is  a  sequence  of 
oral  sepsis  has  not  been  generally  accepted.  A  form  of  alveolar  in- 
flammation, characterized  by  suppuration  extending  deeply  into  the 
sockets  of  the  teeth,  and  called  pyorrhea  or  pyorrhoea  alveolaris,  and 
by  Arkovy,  caries  alveolaris  specifica,  sometimes  induces  an  acute  sup- 
purative inflammation  in,  or  chronic  rarefying  osteitis  of,  the  contiguous 
bone. 

Glossitis,  or  inflammation  of  the  tongue,  is  sometimes  the  result  of 
an  extending  stomatitis  or  arises  in,  and  remains  restricted  entirely 
to,  the  tongue.  The  inflammations  involving  the  surface  of  the  organ 
are  usually  of  the  catarrhal  type.  The  thickness  of  the  epithelial  layers 
of  the  lingual  mucous  membrane,  with  the  irregularity  of  the  papillae, 
gives  rise  to  a  tendency  to  accumulation  of  cells  that  elsewhere  would 
readily  desquamate.  The  inflammation  may  be  acute  or  chronic,  diffuse 
or  circumscribed,  superficial  or  deep.  The  circumscribed  form  is  usually 
dependent  upon  an  irritant  that  directly  affects  the  area  involved. 
Such  irritation  may  be  produced  by  the  sharp  edge  of  a  tooth,  an  ill- 
fitting  dental  plate,  the  pressure  of  a  pipe-stem,  or  the  injury  resulting 
from  long-continued  flow  of  hot  smoke  against  some  part  of  the  tongue. 
Sometimes  the  local  inflammatory  condition  gives  rise  to  considerable 
thickening  of  the  mucosa,   the  thickened  membrane  becoming  white 

'  See  Morbid  Anatomy  of  Syphilis,  and  also  bibliography,  pp.  174  and  177. 
*  See  papers  by   Hunter,   Goadby,   Godlee,   and   discussion  by  a  number  of 
observers  in  the  "  Brit.  Med.  Jour.,"  Nov.  19,  1904,  pp.  1358  to  1372. 


ALIMENTARY   CANAL.  679 

or  bluish-white  in  color;  the  condition  is  commonly  restricted  to  a 
small  area,  to  which  is  applied  the  term  "smoker's  patch,"  or  leuko- 
plakia.' Bockhart  has  seen  sixty  cases  of  buccolingual  leuko]jlakia; 
all  the  ])atients  were  men,  all  smoked,  and  all  were  syphilitics.  Gaucher 
maintains  that  ninety  per  cent,  to  ninety-five  per  cent,  of  the  patients 
have  syphilis. 

Pseudomembranous  glossitis  and  gangrenous  inflammation  of  the 
tongue  are  rare.  Harrington'-  reported  an  instance  of  membranous 
glossitis  that  gave  rise  to  an  exfoliated  cast  of  the  tongue.  The  diph- 
theria bacillus,  streptococci,  and  occasionally  pneumococci,  sometimes 
produce  local  exfoliations  that  resemble  pseudomembrane. 

Inflammation  of  the  tongue  sometimes  begins  in  the  connective 
tissue,  or  the  interstitial  structures  are  involved  secondarily  to  superficial 
inflammation;  the  condition  has  received  the  name  interstitial  glossitis. 
The  process  may  be  chronic  and  associated  wnth  the  jjruduction  of  an 
excess  of  connective  tissue,  or  it  may  be  an  acute  suppurative  lesion, 
which  in  turn  is  sometimes  diffuse,  or  occasionally  accurately  circum- 
scribed, giving  rise  to  what  is  called  lingual  abscess. 

Nigrities  linguae/  parasitic  glossitis,  glossophygia,  or  black  tongttc 
is  an  affection  of  the  tongue  characterized  by  a  blackish,  brownish- 
black,  or  yellowish  coating  developing  near  the  median  line  and  be- 
coming less  intense  as  the  margins  of  the  organ  are  approached.  In 
one  reported  case  the  whole  surface  of  the  tongue  was  involved.  A 
hairy  appearance  is  sometimes  produced  by  prolongation  and  thickening 
of  the  epithelium  of  the  filiform  papillae.  A  number  of  microorganisms 
have  been  observed  in  the  lesions,  but  it  is  not  known  that  the  condition 
is  specific.     The  affection  is  usually  unattended  by  important  symptoms. 

Riga's  disease/  or  sublingual  growth  in  infants,  is  characterized 
by  an  ulcerative  or  pseudomembranous  lesion,  on  the  under  surface 
of  the  tongue  and  involving  the  frenum.  The  process  may  be  pseudo- 
membranous or  ulcerative,  is  probably  of  infectious  origin,  and  due, 
in  part,  at  least,  to  injury  of  the  affected  tissues  by  the  lower  incisor 
teeth.  The  condition  occurs  in  nursing  infants  particularly,  and  appears 
as  an  ulcerative  or  necrotic  process  in  the  area  indicated,  followed  by 
a  granulomatous  growth,  which,  in  some  cases,  resembles  a  papilloma 
or  fibroma.  Evidently  the  new  growth  is  of  inflammatory  origin  and 
probably  may  be  produced  b}^  a  number  of  causes. 

Ludwig's  angina,'  acute  infections  submaxillary  augina,  diffuse 
submaxillary  cellulitis,  and  diffuse  suppuration  of  the  floor  of  the  mouth 
are  names  given  to  a  septic  process  involving  the  tissues  beneath  the 
tongue   and  jaw   and  often  extending  to   the   structures   around   the 

'  Bockhart,  "Monatsch.  f.  prakt.  Derm.,"  Fell.  tr>  May,  1002,  No.  4.  Grancher, 
"La  Presse  Med.."  Julv  8,  1903,  p.  493. 

'"Toronto  Clin.  Soc,"  May  7,  1902:  "Jour.  Amer.  Med.  Assoc  ."  May  24, 
1902. 

'Johnston,  "  N.  Y.  Med.  Jour.."  July  iS.  1903.  p.  126. 

*  Audard,  "Rev.  Mens,  des  Mai.  de  I'Enfance,"  Feb..  1902.  Ainberg.  "Amer. 
Jour,  of  the  Med.  Sci.."  Aug.,  1903,  p.  257.  See  also  papers  in  "Deutsch.  Arch, 
f.  Kinderheilk.,"  1904.  xl. 

'  Munro.  "Boston  Med.  and  Surg.  Jour.,"  Dec.  13,  1900.  de  Santi,  "Royal 
Med.  and  Chir.  Soc.."  Feb.  10,  1903;  "Brit.  Med.  Jour."  Feb.  14,  1903,  p.  369. 
Hamann,  "Wisconsin  Med.  Jour.."  March.  iqo3,  p.  169.  Rol>crtson,  "Amer. 
Med.,"  Dec.  28,  1901.  Semon.  "  Brookl\-n  ^Ied.  Jour."  Jan.,  1905.  Merkcl, 
"Centralbl.  f.  Chir.,"  1904.  xxxi.  No.  48. 


68o 


SPECIAL  PATHOLOGY. 


larynx  and  pharynx  and  sometimes  into  the  cellular  tissues  of  the 
neck.  It  is  probably  closely  related  to,  if  not  identical  with,  the  woody- 
phlegmon  of  the  neck  described  by  the  French  writers.  The  tissues 
of  the  floor  of  the  mouth  become  indurated,  the  tongue  is  forced  up- 
ward and  backward,  and  a  brawny  swelling  occupies  the  submaxillary 
space,  sometimes  extending  to  or  beyond  the  sternocleidomastoid 
muscle,  and,  though  rarely,  downward  to  the  clavicle.     Hamann  has  re- 


-  B 


Fig.  338.— Tongue,  Pharyn.x,  Epiglottis,  etc.,  from  C.\se  of  Ludwig's  Angina  due  to  the  Pneumococcus. 

A.  Upper  margin  of  ulcerated  lingual  lymph-node  (lingual  tonsil).  B.  Lymph-node  at  base  of  anterior  arch; 
this  node  is  eroded  and  almost  dissected  out  by  the  necrotic  process.  C.  Necrotic  tonsil;  the  surface  shows 
depressions  resulting  from  necrosis  of  foUides;  the  corresponding  tonsil  on  the  opposite  side  has  been  cast 
off.  D.  Ulcer  in  the  mucosa;  just  below  this  are  two  prominent  follicles.  £.  One-half  of  ulcerating  pharyn- 
geal tonsil.  The  other  half  can  be  seen  on  the  other  side.  F.  Free  margin  of  the  swollen  and  necrotic  epi- 
glottis. The  leader  from  letter  F  runs  directly  into  the  ulcer  on  one  side.  G.  Glottis  and  upper  part  of  larynx 
containing  corrugated  masses  of  pseudomembrane.     H.  Similar  membrane  on  the  anterior  pharyngeal  wall. 


ported  a  case  in  which  the  infection  resulted  from  pyorrhoea  alveolaris. 
Semon  regards  Ludwig's  angina,  abscess  of  the  pharynx,  erysipelas  of 
the  pharynx,  and  edema  of  the  larynx,  as  closely  allied  manifestations 
of  infection  by  a  number  of  bacteria.  The  organisms  commonly  found 
are  streptococci,  pneumococci,  staphylococci,  and  less  frequently  other 
pyogenic  bacteria.  Infection  usually  occurs  from  ulcers,  necroses,  and 
injuries  in  the  floor  of  the  mouth  or  in  the  pharynx.     In  the  case  re- 


ALIMENTARY   CAN'AL.  68l 

ported  bv  Aldrich  the  primary  lesion  involved  the  frenum  of  the  tonji[ue. 
Microscopic  examination  of  the  alTected  tissue  shows  a  widely  distributed 
edema,  ofteh  some  fibrin,  and  extensive  infiltration  by  polymorpho- 
nuclear leukocytes.  Collections  of  pus  amounting'  to  abscesses  are 
usually  absent.  Pseudomembranous  and  necrotic  j)rocesses  involving 
the  tonsils,  pharynx,  and  larynx  may  accompany  the  condition. 

The  tonsils  are  so  situated  that  they  are  particularly  exposed  to 
infection;'  thcv  also  possess  a  structure  that  specially  adapts  them 
to  the  entrance  of  bacteria.  The  histologic  demonstration  that  the 
surface  is  not  uniformly  covered  by  epithelium,  and  that  bacteria  may 
traverse  the  tonsil  witliout  giving  rise  to  important  structural  altera- 
tions in  the  organ,  render  it  evident  why  infection  of  the  tonsil  is  fre- 
quentlv  manifested  by  lesions  elsewhere  than  in  the  organ. 

Tonsillitis,  also  called  amygdalitis,  is  an  inflammation  of  the  tonsil. 
It  may  be  acute  or  chronic.  sui)crlicial  or  deep;  the  latter  is  sometimes 
called  parenchymatous  tonsillitis.  An  inflammation  of  the  contiguous 
connective  tissue,  frequently  involving  the  tonsil,  is  known  as  periton- 
sillitis, and  is  usually  sui)purative. 

Acute  tonsillitis  may  result  from  infection  by  a  number  of  bacteria ; 
it  mav  be  the  only  conspicuous  local  symptom  of  infection  by  the 
diphtheria  bacillus  and  also  results  from  the  local  action  of  streptococci, 
staphylococci,  or  pneumococci.  Darieu"  states  that  three  per  cent,  of  the 
cases  are  due  to  the  pneumococcus.  The  tonsillar  enlargements  ac- 
companying influenza  are  probably  induced  by  the  Pfeiffer  bacillus 
(Kamen).  Tonsillar  inflammation  may  be  due  to  the  spirillum  of  Vin- 
cent (see  p.  173).  The  bacteriology  of  the  condition  indicates,  and  a 
clinical  study  of  cases  shows,  that  the  affection  is  often  contagious. 
Those  afflicted  by  rheumatism  or  gout  seem  particularly  susceptible 
to  the  condition.  In  scarlet  fever,  measles,  smallpox,  and,  less  fre- 
quently, typhoid,  definite  tonsillar  swelling  and  sometimes  fully  de- 
veloped tonsillitis  occur.  When  inflamed,  the  tonsil  is  red,  swollen, 
tender,  and,  in  the  earlier  stages,  the  surface  is  dry  and  glazed.  The 
superficial  change  may  be  that  of  a  catarrhal  inflammation.  Often 
the  crvpts  are  distended  by  a  white,  or  creamy  white,  semisolid  exudate. 
justifying  the  name  lacunar  or  follicular  tonsillitis. 

Tonsillar  abscess,  suppurative  interstitial  tousillitis,  or  quinsy  is 
an  acute  inflammation  of  the  tonsil  attended  by  the  formation  of  pus 
in  the  interior  of  the  organ.  It  probably  results  from  infection  through 
the  crypts  and  sometimes  follows  acute  follicular  inflammation.  The 
suppuration  mav  arise  in,  or  extend  to,  the  peritonsillar  tissue,  and 
occasionallv  involves  the  submucosa  of  the  contiguous  pharynx.  Ca- 
tarrhal and  also  follicular  tonsilhtis  is  commonly  bilateral;  the  sup- 
purative or  phlegmonous  lesion  rarely  involves  both  sides  simultane- 
ouslv. 

Chronic  tonsillitis  is  characterized  by  an  inflammation  of  slight 
intensity  extending  over  a  long  period.     In  some  cases  the  follicles  are 

»  Hoche.  "Revue  Med.  I'CEst,"  Oct.  i,  1902.  Kamen,  'Centralbl.  f.  Bakt.." 
Nov.  :5o,  1903.  p.  150.  Wood.  •Univ.  of  Penna.  Met!.  Bull."  Uct.,  1904.  Gurich. 
•Munch,  med.  Woch."  Nov.  22,  1904,  p.  2089.  Wright.  'Med.  News,"  March 
4,  1905,  p.  385.  Fredrick.  "California  State  Jour,  of  Med.,"  1905.  iii,  43,  No.  2. 
See  also  p.  91,  and  Ingestion  Tuberculosis,  p.  149. 

'  These  de  Lyon.  1902. 


682  SPECIAL  PATHOLOGY. 

particularly  involved  and  the  parenchyma  but  slightly  altered;  this 
form  is  called  chronic  lacunar  tonsillitis.  The  chronic  interstitial  ton- 
sillitis may  be  hyperplastic  or  fibroid.  The  former  is  attended  by 
notable  increase  in  the  lymphoid  tissue  of  the  organ,  and  proliferation 
of  the  endothelial  cells  lining  the  lymph-sinuses.  The  resulting  struc- 
ture is  soft  and  histologically  identical  with  postnasal  adenoids,  de- 
scribed on  p.  567.  In  other  cases  the  conspicuous  alteration  is  an 
increase  in  the  fibrous  tissue,  rendering  the  tonsil  firm  and  later,  by 
contraction,  atrophied.  This  condition  may  come  on  insidiously  or 
follow  the  hyperplastic  form. 

Tuberculosis  of  the  tonsil'  probably  occurs  more  frequently  than 
the  clinical  studies  indicate.  Friedmann,  in  an  examination  of  145 
cases,  found  the  tonsil  tuberculous  in  17,  of  which  12  were  primary. 
The  affected  tonsil  may  be  of  normal  size  and  frequently  the  histologic 
lesions  of  tuberculosis  are  absent.  In  such  cases  the  diagnosis  rests 
upon  the  demonstration  of  tubercle  bacilli,  preferably  by  animal  in- 
oculation. Koplik  believes  that  whenever  the  cervical  lymph-nodes 
are  the  seat  of  tuberculosis,  without  evidence  of  general  infection,  we 
mav  safely  conclude  that  the  bacillus  entered  through  the  tonsil. 

Actinomycosis  of  the  tonsiP  is  exceedingly  rare.  Cheattie  and 
Emery  state  that  the  instance  they  report  is  probably  the  second 
authentic  case. 

Pharyngitis,  or  inflammation  of  the  pharynx,  also  called  angina, 
results  from  infection  by  a  number  of  organisms  and  accompanies  the 
infectious  diseases  in  which  throat  lesions  are  common.  It  may  be 
due  to  the  diphtheria  bacillus,  pneumococcus,  streptococcus,  spirillum 
of  Vincent,  and  occasionally  Friedlander's  bacillus.  According  to  Cion- 
nini,^  there  are  twenty -four  recorded  cases  due  to  the  pneumobacillus. 
There  are  a  number  of  predisposing  causes  influential  in  the  production 
of  pharyngeal  inflammation.  These  include  exposure  to  cold,  chilling, 
irritation  by  tobacco,  and  the  inhalation  of  irritating  fumes.  Pharyn- 
geal inflammation  is  said  to  be  particularly  frequent  in  the  gouty  and 
rheumatic,  and  in  patients  afflicted  by  chronic  renal  inflammation. 
The  chronic  forms  are  especially  common  among  alcoholics,  who  are 
also  abnormally  susceptible  to  acute  attacks.  Several  forms*  of  the 
affection  are  recognized. 

Acute  catarrhal  pharyngitis  is  manifested  by  redness,  dryness,  and 
swelling  of  the  mucous  membrane,  followed  by  a  catarrhal  exudate. 
Cellular  infiltration  of  the  submucosa  is  frequently  marked.  The 
palatine  arches  and  the  uvula  usually  participate  in  the  process.  After 
a  few  days  the  mucosa  is  bathed  in  an  inflammatory  exudate,  the 
epithelium  desquamated,  and  the  submucous  vessels  conspicuous.  The 
condition  may  be  prolonged  in  the  subacute  form,  or  repeated  attacks 
may  lead  to  chronic  pharyngitis. 

Chronic  pharyngitis,  also  called  chronic  pharyngeal  catarrh,  fre- 
quently follows  the   acute,   particularly  when  the  constitutional   con- 

*  Glas,  "Wien.  klin.  Woch.,"  1903,  No.  36.  Koplik,  "Ainer.  Jour,  of  Med. 
Sci.,"  Nov.,  1903,  p.  816.      Kingsford,  "  Lancet,"  Jan.  9,  1904,  p.  89.  -■»*'\ 

^Cheattie    and    Emery,    "  Laryngological    Soc.    of    London,"    Nov.    4,    1904; 
"Lancet,"  Nov.  19,  1904,  p.  1426.     Thevenot,  "Gaz.  des  Hop.,"  Nov.  27,  1904. 
^  "Rif.  Med.,"  June  17,  1903. 

*  See  Inflammations  of  Mucous  Membranes,  p.  546. 


ALI.MKX TAKY    CAN'AI..  68.? 

ditions  mentioned  above,  favor  prolongation  of  the  affection.  In  child- 
hood and  adolescence  the  condition  is  comincnily  a  manifestation  of 
adenoids  (see  p.  567).  Pharyngeal  catarrh  is  sometimes  associated 
with  chronic  tonsillar  inflammation  and  generally  accompanies  post- 
nasal catarrh.  The  surface  of  the  mucosa  is  spotted  here  and  there 
by  an  accumulation  of  thick,  grayish  mucus.  The  reddening  may  not 
be  marked,  although  in  some  cases  the  hyperemia  persists.  Cellular 
infiltration  of  the  submucosa,  and  proliferation  of  the  lymphoid  tissue, 
may  greatly  thicken  the  membrane,  giving  rise  to  the  condition  called 
hyperplastic  or  hypertrophic  pharyngitis.  The  atrophic  form,  also 
known  as  pharyngitis  sicca,  is  often  a  later  stage  of  the  preceding  or 
may  arise  independently.  The  mucous  membrane  is  usually  not  so 
intensely  hyperemic,  is  dry,  and  often  appears  wasted.  The  discharge 
is  more  tenacious,  and  adheres  closely  to  the  mucosa.  Granular  areas 
containing  hyperplastic  lymphoid  tissue  are  sometimes  present. 

Pseudomembranous  pharyngitis  is  usually  diphtheric,  but  may  be 
produced  by  any  of  the  organisms  mentioned  above.  In  manv  cases 
the  membrane  formation  is  primary  in  the  pharynx ;  in  other  instances 
it  develops  from  extension,  the  lesions  beginning  on  the  tonsils,  or  less 
commonly,  on  the  buccal  mucosa. 

Phlegmonous  pharyngitis  may  be  diffuse  or  circumscribed;  the 
fonner  is  an  infection  of  the  submucosa  which  gives  rise  to  an  extensive 
infiltration  by  polymorphonuclear  leukocytes.  The  structural  changes 
occurring  in  the  submucosa  are  essentially  similar  to  the  interstitial 
alterations  of  the  connective  tissue  observed  in  Ludwig's  angina.  The 
circumscribed  form  of  the  lesion  is  called  pharyngeal  abscess  and  is 
usually  located  between  the  mucosa  and  the  vertebra?.  It  is  said  to 
be  more  frequent  in  the  rickety  and  tuberculous,  and  in  the  debilitated; 
it  may  be  secondary  to  vertebral  disease  or  follow  nonsuppurative 
pharyngeal  inflammations.  Semon  states  that  it  may  be  produced  bv 
blows  or  injuries,  and  probably  results  from  suppurative  inflammation 
of  the  submucous  lymjihoid  tissue. 

Pharyngomycosis  leptothricia'  is  a  rare  affection  of  the  pharyngeal 
mucous  membrane. 

Tuberculosis  of  the  pharynx  may  be  acute  or  chronic,  primarv  or 
secondary.  But  few  cases  of  the  primary  form  have  been  reported. 
In  an  occasional  case  of  acute  miliary  tuberculosis  tubercles  can  be 
detected  in  the  pharynx  and  uvula.  The  usual  form  of  pharvngeal 
tuberculosis  is  a  chronic  ulcerative  process,  attended  by  the  formation 
of  nodular  granulations  and  ulcers,  and  is  secondary  to  pulmonarv 
infection. 

S)rphilis  of  the  pharynx  may  be  characterized  by  more  or  less  specific 
lesions  of  the  disease  or  be  manifested  by  acute,  or,  more  commonly, 
chronic,  pharyngeal  catarrh.  Pharyngeal  chancres  are  rare.  During 
the  secondary  stage  of  syphilis  erythematous  reddening  and  mucous 
patches  are  not  infrequently  present;  the  latter  may  be  bilateral  and 
symmetric.  The  gumma  of  the  tertiary  period  involves  the  posterior 
pharyngeal  wall  as  a  sessile  induration,  which  may  progress  to  softening 
and  ulceration.  The  resulting  ulcer  is  rather  deep,  crater-like,  and 
possesses  perpendicular  edges,  and  sometimes  an  undermined  margin. 
The  floor  of  the  ulcer  frequently  contains  necrotic  tissue  and  gravish, 
'  See  Leptothricosis,  p.  1.70. 


684  SPECIAL  PATHOLOGY. 

mucopurulent  material.  Occasionally  ulcers  arise  independently  of 
gummata,  although  upon  this  point  authorities  are  not  agreed.  The 
cure  of  such  ulcers,  or  the  cicatrization  of  gummata,  may  leave  thin, 
grayish  scars  in  the  pharyngeal  mucosa. 

Diphtheria^  is  one  of  the  most  common  of  the  grave  infections  in- 
volving the  tonsils,  pharynx,  nose,  and  laryngeal  mucosa.  It  may 
attack  the  lips,  gums,  and  buccal  mucosa,  as  well  as  the  structures  just 
mentioned.  Of  the  220  cases  examined  by  Councilman,  Mallory,  and 
Pearce,  a  definite  membrane  was  present  in  127.  It  was  on  the  tonsils 
in  65;  epiglottis,  in  60;  larynx,  in  75;  trachea,  in  66;  pharynx,  in  51; 
mucosa  of  nares,  in  43;  bronchi,  in  42;  soft  palate,  including  uvula, 
in  13;  esophagus,  in  12;  and  on  the  tongue  in  9.  Burrows  states 
that  in  1528  cases  of  diphtheria  the  membrane  was  on  both  tonsils; 
in  243  cases  on  one  tonsil;  in  404  cases  on  the  uvula;  in  173  cases  on 
the  posterior  pharyngeal  wall;  in  244  cases  on  the  palate;  in  12  patients 
the  lips  were  involved,  and  in  3  the  tongue.  The  membrane  occurred 
in  the  nose  in  71;  the  inner  surface  of  the  cheek,  external  auditory 
canal,  outer  canthus  of  eye,  and  vulva  were  each  involved  in  one  instance. 
It  is  to  be  remembered  that  infection  by  the  Klebs-Loffier  bacillus 
mav  be  manifested  by  catarrhal,  gangrenous,  or  pseudomembranous 
lesions.^  In  typic  cases  there  is  a  marked  hyperemia,  followed  by 
exudate  in  thesubmucosa,  which  commonly  produces  a  notable  swelling. 
Fluid  portions  of  this  exudate,  and  often  many  leukocytes,  pass  through 
the  surface,  undergo  necrosis,  and  form  the  membrane;  the  necrosis 
may  extend  into  the  submucosa  and  involve  the  contiguous  tissues. 
This  process  gives  rise  to  a  grayish  or  grayish-yellow,  dirty  membrane, 
or  when  thicker  it  may  be  almost  black.  Separation  of  the  dead  tissue 
occasionally  produces  definite  ulcers.  In  the  earher  stages  the  margin 
of  the  necrotic  tissue  is  indefinitely  outlined,  but  when  separation  has 
begun,  the  periphery  is  often  sharply  defined.  The  visceral  lesions  of 
the  affection  will  be  found  enumerated  on  page  120.  Mixed  infections 
are  the  rule,  the  concurrent  bacteria  being  streptococci,  staphylococci, 
and  pneumococci.  The  glandular  enlargements  accompanying  the 
disease  are  due  to  the  action  of  toxins  or  the  entrance  of  associated 
bacteria.  Chronic  diphtheria  may  result  from  prolongation  of  an  acute 
attack,  the  bacillus  remaining  in  the  discharges  from  the  affected  mucosa; 
or,  as  originallv  pointed  out  by  Concetti,  the  affection  may  be  chronic 
from  the  beginning,  at  no  time  manifesting  the  virulent  phenomena 
of  typic  acute  diphtheria.  In  these  cases  the  pharynx  or  nasal  mucosa 
is  siightlv  reddened,  and  pseudomembrane  formation  is  inconspicuous 
or  absent.  In  Xeufeld's  case  virulent  bacilli  were  present  for  five 
months.  Symptoms  of  systemic  intoxication  are  usually  absent.  The 
late  Dr.  Packard  referred  to  such  cases  as  hacteriologic  diphtheria,  dis- 
tinguishing them  from  the  more  evident  forms,  which  he  called  clinical 
diphtheria.  Pavlovskiy  proposes  for  this  form  of  infection  the  name 
diphtheromycosis.  A  small  percentage  of  cases  of  chronic  follicular 
tonsillitis  belong  with  this  group. 

1  See  p.  118.  Also  Councilman,  Mallorv,  and  Pearce,  "A  Study  of  the  Bac- 
teriology- and  Pathology  of  Two  Hundred  and  Twenty  Fatal  Cases  of  Diphtheria," 
1900.  Pearce,  "Proceed.  Path.  Soc.  of  Phila.,"  June,  1901.  Neufeld,  '"Deut. 
med.  Woch.,"  May  12,  1904.      Burrows.  "Amer.  Jour,  of  Med.  Sci.,"  Feb.,  1901. 

^  See  Inflammation  of  Mucous  Membrane,  p.  546. 

'"Roussky  Vratch,"  Jan.  29,  1903. 


ALIMENTARY   CANAL.  685 

Under  the  name  diphtheroid  angina'  or  pseudodiphtheric  angina 
are  included  a  number  of  conditions  clinically  and  anatomically  re- 
sembling diphtheria,  but  due  to  causes  other  than  the  Klebs-Loffler 
bacillus.  Hill  found  that  in  1251  cases,  clinically  diagnosed  diph- 
theria, cultures  from  37.25  ])er  cent,  did  not  yield  the  diphtheria  bacil- 
lus. Less  than  half  of  the  cases  examined  by  Michclazzi  contained  the 
Klebs-Lottter  bacillus.  The  organisms  producing  this  condition  are 
pneumococci,  stre])tococci,  staphylococci,  bacillus  of  Friedlander,  and, 
less  commonly,  other  organisms.  The  lesions  in  many  cases  can  not 
be  differentiated  from  those  depending  upon  the  diphthena  bacillus. 
The  systemic  phenomena  are  usually  less  marked,  but  even  this  cri- 
terion is  untrustworthy.  It  is  probable  that  many,  if  not  all,  of  these 
forms  are  as  communicable  as  true  diphtheria. 

Tumors  of  the  Mouth  and  Pharynx.^ — An  interesting  abnormality 
is  sometimes  seen  at  the  base  of  the  tongue  at  or  near  the  point  where 
the  thvroglossal  duct  once  opened.  This  consists  of  a  tumor-like  forma- 
tion composed  of  more  or  less  normal  thyroid  tissue,  and  is  called  lingual 
goiter.  Its  unusual  position  is  dependent  upon  the  fact  that  during 
fetal  life  the  duct  of  the  gland  opened  at  this  point,  and  ectopic  portions 
of  thyroid  tissue,  undergoing  hypertrophy  later  in  life,  give  rise  to  dis- 
tinct tumors  usually  of  the  adult  epithelial  type.  Fapilloinata  occur  on 
the  tongue  and  cheek,  rarely  in  the  posterior  part  of  the  mouth  or  in  the 
pharynx.  Adenomata  may  involve  the  tonsil,  and  occasionally  the 
pharyngeal  wall;  Theisen^  has  collected  the  cases  of  lipoma  of  the 
tonsil,  of  which  six  are  recorded.  Of  the  embryonic  epithelial  tumors, 
the  sqiianioits  epithelioma  is  the  most  common;  its  usual  seat  is  upon 
the  tongue  or  lips,  more  commonly  the  latter;  squamous  epithelioma 
of  the  lip  is,  of  all  forms  of  cancer,  the  most  frequent.  Of  the  350 
cases  observed  by  Stoker,  but  three  occurred  in  women;  the  three 
females  were  smokers.  In  4  cases  the  tumor  was  situated  in  the  upper 
lip.  He  has  not  observed  the  condition  in  patients  under  thirty  years 
of  age.  Of  the  34  cases  of  cancer  of  the  tongue  reported  by  Boyd  and 
Unwin,  27  began  in  some  part  of  the  organ  and  7  arose  in  the  frenum; 
3  of  the  patients  were  women;  the  youngest  was  forty-two  years. 
Hutchinson  believes  that  in  thirty  per  cent,  of  the  cancers  of  the  tongue 
there  is  a  history  of  syphilis.  Rodieger*  states  that  in  30  cases  of  lingual 
cancer  the  first  manifestation  was  a  nodule  in  14  and  an  ulcer  in  10. 
Butlin  and  Spencer  describe  a  form  of  atrophic  cancer  of  the  tongue; 
in  one  of  the  reported  cases  the  right  half  of  the  tongue  was  completely 
withered  and  the  secondary  deposits  also  showed  atrophy.  Fripp  and 
Swan  have  analyzed  44  recorded  cases  of  sarcoma  of  the  tongue,  of 
which  they  think  but  29  are  certainly  of  this  nature.  The  largest  re- 
corded specimen  weighed  400  gm. ;  a  pedunculated  form  of  lingual 
sarcoma  has  been  observed.  Pharyngeal  ])olyps  and  sessile  tumors 
of  the  pharyngeal  wall  are  rare.    Dermoid  tumors  of  the  tongue,  pharynx, 

»  Michelazzi.  "II  Policlinico."  Rome.  1004,  No.  9.  Testevin  and  Busquct. 
"La  Presse  Mod,"  Sept.  t,.  1004.  p.  565.  Hill.  "Boston  Med.  and  Surij.  jour." 
Dec.  15,  1904.  Vincent,  "Lancet."  May  18,  1905.  p.  1260.  See  also  ulceromem- 
branous stomatitis,  p.  173;  Diplococcus  pneumbnijr,  p.  109;  and  streptococcus 
infections,  p.  1 1  <;. 

'  "The  Practitioner."  May.  1903,  is  largely  devoted  to  tumors  of  the  mouth. 

'  "  LarsTijjoscope,"  Aujj..  190  v 

*  "Beitr.  z.  klin.  Chir.,"  Bd    xjci.  H.  2. 


686  SPECIAL  PATHOLOGY. 

and  buccal  floor  are  occasionally  observed.  The  lymphangiectases 
have  been  described  (see  p.  674).  Of  the  adult  connective-tissue 
tumors,  lipomata,  fibromata,  myomata,  chondromata,  hemangiomata,  and 
lymphaugiomata  occur.  The  last  of.  these  occur  as  tnacrocheilia,  or 
lymph  lip,  and  macroglossia,  or  lymph  tongue;  these  conditions  are 
sometimes  spoken  of  as  lymphangiectases ,  or  dilatations  of  the  lymph- 
atics in  the  tongue  and  lip  respectively.  Of  the  sarcomata,  or  embryonic 
connective-tissue  tumors,  but  few  occur  in  the  mouth;  myeloid  sarcoma 
of  the  lower  jaw  is  the  most  common  form. 

An  epulis  is  a  tumor  situated  on,  or  springing  from,  the  gum.  It 
may,  therefore,  be  a  papilloma,  carcinoma,  fibroma,  sarcoma,  or  other 
tumor  in  that  situation.  In  a  statistical  study  of  118  tumors  of  the 
upper  jaw  Stein^  found  that  64  patients  were  men;  forty-nine  per  cent, 
of  the  tumors  were  carcinomata  and  twenty  per  cent,  sarcomata.  He 
states  that  cancer  usually  begins  in  the  antrum  of  Highmore  and  sar- 
coma in  the  alveolar  process.  Giant-cell  sarcoma  of  the  jaw  is  one 
of  the  frequent  neoplasms  involving  the  mouth.  (See  p.  354.)  Refer- 
ence has  already  been  made  to  pharyngeal  and  postnasal  adenoids. 
(See  p.  567.)  A  neoplasm  of  vast  surgical  and  clinical  importance  is 
the  retropharyngeal  sarcoma — a  tumor  springing  from  the  submucosa 
or  osseous  structures  of  the  pharyngeal  vault.  It  usually  attains  a 
high  degree  of  malignancy,  and  its  peculiar  location  renders  removal 
difficult.     Endotheliomata  of  the  pharynx  and  tonsil  are  infrequent. 

SALIVARY  GLANDS. 

Parotitis,  or  mumps,  is  an  infectious  inflammation  occurring  in  the 
parotid  gland.  It  is,  no  doubt,  due  to  some  form  of  infection,  although 
the  exact  nature  of  the  infectious  agent  has  not  been  demonstrated. 
A  chronic  infection  may  occur  in  any  of  the  salivary  glands.  The 
parotid  seems  more  or  less  susceptible  to  septic  influences,  and  is  not 
infrequently  inflamed  during  septic  diseases,  and  occasionally  in  or- 
dinarv  febrile  prcPcesses;  the  condition  is  referred  to  as  parotid  bubo. 
Acute  inflammation  of  the  parotid  gland  sometimes  follows  operation, 
particularly  on  the  abdomen." 

A  similar  suppurative  condition  is  sometimes  observed  in  the  sub- 
lingual and  submaxillary  glands.  In  the  last  two  organs  the  suppura- 
tion may  be  secondary  to  infections  of  the  surrounding  tissues.  (See 
Ludwig's  Angina.)  So  far  as  known,  the  suppurative  interstitial  inflam- 
mations are  the  only  examples  of  pure  interstitial  disease  in  its  acute 
form  affecting  these  organs. 

Chronic  Interstitial  Parotitis  {Parotid  Sclerosis,  Fibroid  Parotid, 
Indurative  Parotitis,  etc.). — A  study  of  salivary  secretion  made  by 
Dickinson,  who  frequently  catheterized  the  duct  and  showed  that  often 
the  salivarv  output  was  materially  below  the  normal,  and  the  histologic 
studies  made  by  Harris,  who  demonstrated  the  chronic  fibroid  changes 
in  the  salivary  glands,  all  point  to  the  fact  that,  like  the  pancreas, 
liver,  and  kidnev,  these  organs  are  liable  to  chronic  interstitial  over- 
growth comparable  to  that  seen  in  the  other  organs  just  mentioned. 
(See  Figs.  339  and  340.) 

1  "Arch.  f.  klin.  Chir.,"  1902,  Bd.  65. 

^  Morley,  "Amer.  Gynecology-,"  Dec,  1902.  Wagner,  "Wien.  klin.  Woch.," 
1904,  No.  54. 


A  L I  M  !•:  N  T  A  U  Y    C  A  N  A  I. . 


687 


Mikulicz  described  a  chronic  symmetric  enlari,'oment  of  the  lacrimal 
and  parotid,  and  sometimes  involving  the  sublingual  glands.  The 
parotids  may  be  quite  prominent;  the  condition  usually  shows  no  ten- 
dencv  toward  sui)i)uration,  and  the  general  nutrition  of  the  patient  is 
unintluonced.  Tictze  has  found  a  parasite,  thought  to  be  a  protozoan, 
in  the  tissues.     The  condition  is  called  Mikulicz's  disease.' 

Hypersecretion,  sialorrhea,  or  ptyalism  usually  occurs  in  inflamma- 
tions of  the  mouth,  as  a  symptom  of  chronic  poisoning  by  mercury, 
phosphorus,  or  copper,  and  as  a  physiologic  result  of  the  administrations 
of  jaborandi  and  certain  iodin  compounds;  it  is  also  present  in  hydro- 
phobia and  in  other  diseases,  both  acute  and  chronic,  primarily  or 
secondarily  involving  the  nervous  system:  e.  g.,  hysteria,  trifacial  neuri- 
tis, optic  neuritis  C^),  and  sometimes  late  in  tabes.     The  reverse  of  the 


Fic.  330.— Sectio.v  from  Rioht  I'arotid."     (Carlx)I-toluidin-blue  and  eosin.    Bausch  and  Lomb,  i-inch  Oc.  B.) 
a,  a.  Normal  lobules,      b.  Thickened  trabecul.x-.     c.  Cellular  infiltration  into  a  lobule,     d.  A  duct  the  wall  of 

which  is  thickenoi  and  inliltratcd  with  cells,  and  the  lumen  decrea.sed  in  size.       e.  \n  artery  with  ceilular 

infiltration  into  its  walls. 


preceding — dry  mouth,  ai)tyalism,  xerostonia — has  been  observed;  the 
exact  cause,  however,  is  not  known;  it  is  said  to  be  a  symptom  of 
diabetes. 

Sialolithiasis,  or  calculous  disease  of  the  salivary  glands,  is  attended 
bv  the  production  of  definite  concretions  usually  situated  in  the  ducts. 
The  stones  are  chiefly  composed  of  carbonate  and  i)hosphate  of  cal- 
cium, and  are  most  common  in  the  submaxillary  glands  or  ducts;  their 
localization  in  the  latter  structures  is  usually  attributed  to  the  large 
amount  of  mucin  in  the  secretion  of  these  glands,  and  to  the  fact  that 
the  mouths  of  the  ducts  are  so  situated  that  infection  or  foreign  bodies 

•  Cheinisse.  "La  Seni.  Med.,"  Jan.  25,  1905.  p.  .57.  Tietze.  "Mittheil.  a.  d. 
Grenzgehiet.  de  Med.  u.  Chir."  xiv.  No.  3. 

'Case  re]iortc<l  by  Harris,  "Boston  Medical  aii'l  Surgical  Journal."  May  18, 
1899. 


688 


SPECIAL  PATHOLOGY. 


may  enter.  The  calculi  vary  in  size  from  the  so-called  salivary  sand 
to  masses  2  cm.  or  more  in  length  and  i  cm.  in  thickness;  in  the  case 
reported  by  Puzey  the  stone  weighed  7.5  gm.  They  are  commonly 
attended  b}^  inflammation,  which  may  be  suppurative,  and  sometimes 
perforates  the  cheek  or  floor  of  the  mouth,  giving  rise  to  a  fistula. 
Jarecky^  has  been  able  to  collect  213  cases  of  salivary  calculus.  It  is 
suggested  that  they  are  of  bacterial  origin,  and  a  number  examined 
have  been  found  to  contain  microorganisms.  They  frequently  recur 
after  removal.  The  concretions  resulting  from  infection  or  accumulated 
exfoliated  cells  or  food-particles  at  the  gingival  margins  are  of  a  similar 
nature. 

Obstruction  to  the  duct  of  a  salivary  gland  gives  rise  to  a  retention 
cyst  known  as  a  ranula  ;  these  are  usually  named  after  the  gland  in- 
volved,   as    ranula    snbinaxillaris,    ranula    rctromaxillaris ,    and    rantila 


Fig.  340. — Section  of  the  Left  Parotid  under  a  Very   Low  Power.-      (Carbol-toluidin-blue  and  eosin.) 

a,  a.  Normal  lobules,     b,  b.  Greatly  thickened  trabeculae.     c.  Lobule  almost  entirely  replaced  by  fibrous  tissue. 

The  process  is  more  recent  in  figure  339. 

sublingualis.  The  classic  ranula,  so  long  considered  a  cyst  of  the  duct 
of  Wharton,  is  now  beHeved  to  be  a  mucous  cyst  in  the  Blandin-Nuhn 
gland. 

Tuberculosis  of  the  salivary  glands^  is  of  infrequent  occurrence. 
According  to  Fiorani,  it  may  be  diffuse  or  confluent,  and  the  form 
observed  in  man  corresponds  to  that  produced  by  duct  infection  in 
lower  animals.  Of  the  nine  cases  collected  by  Wood,  in  three  it  was 
thought  that  the  infection  was  by  Steno's  duct,  one  from  an  adjacent 
lymph-node,  one  from  the  blood,  and  in  four  the  route  of  infection 
was  undetermined. 


*  "Med.  News,"  Feb.  18,  1905,  p.  304. 

^  Case  reported  by  Harris,  "Boston  Medical  and  Surgical  Journal,"  May  18, 
1899. 

3  Wood,  "Univ.  of  Penna.  Med.  Bull.,"  Dec.  19.  1903.  Fiorani,  "  Rif .  Med.,  ' 
Aug.  27,  1904. 


AI.IMKNTAKY   CANAL. 


68() 


Tumors  of  the  salivary  glands  are  not  common.  Of  the  adult  epithe- 
lial type,  iidoioniala  ottasionally  occur;  they  are.  however,  exceedingly 
rare.  Of  the  embryonic  epithelial  tis.sue  tumors  or  cancers,  epithe- 
liomata  are  the  most  frequent,  and  these,  histoloifically,  are  usually 
of  the  tubular  variety,  althouj^^h  squamous  epithelioma  has  been  ob- 
served. Eiucplialoid  and  scirrlius  are  rare.  Of  the  adult  connective- 
tissue  tumors,  cho)idro}>iata,  fibroiinitd.  and  luyonidla  occasionally  occur. 
Fibromata  containini,' 
more  or  less  glandular 
structure  —  hbroadeno- 
mata  —  are  sometimes 
observed.  The  ordinary 
types  of  sarcoma  are 
rarely  primary  in  the 
salivary  glands.  The 
most  frequent  of  the 
parotid  neoplasms  is  the 
so-called  mixed  tumor  ^ 
of  the  gland.  It  seems 
likely  that  more  than 
one  form  of  new  growth 
has  been  included  under 
this  name;  most  of  the 
mixed  tumors  are  endo- 
theliomata.  It  is  possi- 
ble that  some  of  them 
are  teratomata.  They 
are  slowly  growing  neo- 
plasms that  after  'years 
of  indolent  enlargement 
may  suddenly  develop 
rapidly  and  assume  the 
characters  of  actively 
malignant  tumors. 
They  are  usually   firm, 

often  quite  hard,  frequently  bossed,  and  not  uncommonly  contain  cysts. 
In  the  earlier  stages,  and  often  when  the  tumor  is  growing  rapidly,  a 
thick  fibrous  cap.sule  may  be  demonstrable.  Cartilage  or  chondroid 
tissue,  and  fibrous  and  myxomatous  areas,  are  usually  present.  Histo- 
logically many  of  these  tumors  are  typical  endotheliomata,  usually  of 
the  lymph-vessel  type.     (See  p.  358.) 


Fig.  341. —  .\li.\ED  Tumor  of  the  Parotid  Gland. 
Weight  of  tumor,  including  contained  fluid.  al>out  .^.5  kilos.  The  pa- 
tient recovered.  (Case  reported  by  Dr.  W.  \V.  Keen,  in  "Jour. 
Am.  .\Ied.  .Assoc."  ,\pril  30,  IQ04.)  .1.  Large  Ikis.s,  upon  the  lower 
margin  of  which  arc  two  ^joints  of  softening.  M.  Softened  (necrotic) 
areas  overlying  cystic  spaces. 


ESOPHAGUvS. 

Normal  Structure. — From  the  pharynx  to  the  anus  the  essential 
structure  of  the  musculomembranous  tube — the  alimentary  canal — is 
that  of  a  mucous  membrane  resting  upon  a  muscular  wall  composed 
of  two  or  more  layers  of  unstriped  muscle-fiber.  The  variations  at 
different  points  usually  consist  in  different  glandular  and  epithelial 
layers,  but  the  esophagus  differs  in  its  muscular  layer  from  the  re- 

'  Johnson  and  Lawrence.  "Trans.  Path.  Soc.  of  London."  1903,  vol.  54,  p. 
329.     Wood,  "Annals  of  Surgery,"  Jan.  and  Feb..  1904,  pp.  57  and  207. 

45 


690  SPECIAL  PATHOLOGY. 

mainder  of  the  tube,  in  that  the  upper  part  possesses  little  or  no  un- 
striated  muscle,  while  the  muscle  present  in  the  lower  end  is,  like  that 
in  the  remainder  of  the  alimentary  canal,  composed  exclusively  of  un- 
striped  fibers.     The  epithelium  of  the  esophagus  is  stratified  throughout. 

Malformations  of  the  esophagus^  are  rare;  probably  not  more  than 
seventy-five  instances  are  on  record.  In  the  larger  number  of  cases 
the  malformation  is  the  result  of  partial  absence,  or  failure  of  the  two 
parts  to  fuse  in  a  normal  manner.  Sometimes  the  upper  and  lower 
sacs  are  joined  by  a  fibrous  cord  and  there  is  no  communication  with 
the  trachea.  In  another  form  the  upper  end  of  the  lower  segment 
opens  into  the  trachea  or  into  a  bronchus.  Congenital  fistulae  in  the 
neck,  and  also  cysts  communicating  with  the  esophagus,  are  by  some 
classed  with  the  malformations  of  the  organ.  I  have  referred  to  them 
elsewhere  as  branchial  cysts  and  fistulae.  (See  p.  674.)  Renault  and 
Sebilleau  apply  the  name  duplication  to  a  condition  in  which  part  of 
the  esophagus  is  divided  into  two  tubes  which  usually  unite  above  and 
below.  Congenital  atresia  is  most  frequent  in  the  upper  esophagus, 
and  stenosis,  of  developmental  origin,  commonly  affects  the  same  area. 
Whipham  and  Fagge  have  been  able  to  collect  but  six  cases  in  which 
the  lower  end  of  the  esophagus  was  narrowed.  Sievers  reports  an 
instance  of  dilatation  of  the  esophagus  which  he  attributes  to  con- 
genital defect.  The  demonstration,  by  a  number  of  observers,  and  more 
recently  by  Schridde,  Ruckert,  and  Schwalbe,  of  islands  of  gastric 
mucosa  and  glands  similar  to  those  of  the  cardia  and  pylorus  in  the 
esophageal  wall,  suggests  an  explanation  for  the  occurrence  of  cysts, 
sometimes  found  in  the  esophagus,  and  also  for  peptic  ulcers,  of  which 
Kraus  has  collected  twenty  cases  in  which  the  esophagus  was  involved. 

Anemia  of  the  esophagus  is  usually  a  part  of  general  anemia.  Hy- 
peremia occurs  in  the  initial  stage,  and  accompanies  inflammation  of 
the  organ.  Congestion  is  marked  in  the  venous  distention  of  chronic 
heart  disease  and  pulmonary  obstruction,  such  as  emphysema  and  fibroid 
pneumonia.  A  condition  closely  allied  to  congestion  is  varicosity  of 
the  esophageal  veins.  This  is  usually  dependent  upon  venous  obstruc- 
tion in  the  liver,  as  observed,  for  example,  in  cirrhosis.  Anastomosis 
between  the  lower  esophageal  veins  and  the  veins  of  the  stomach  affords 
egress  for  the  blood,  which  would  otherwise  be  forced  to  pass  through 
the  contracting  liver.  Rupture  of  the  dilated  veins  in  the  esophagus 
may  give  rise  to  fatal  hemorrhage. 

Esophagitis — ;inflammation  of  the  esophagus — usually  results  from 
injury.  Catarrhal,  hemorrhagic,  and  gangrenous  processes  follow  the 
application  of  corrosive  substances,  such  as  strong  acids,  alkalies  and 
cauterants,  mercury,  salts  of  copper,  etc.;  scalds  and  burns  induce 
similar  changes.  The  severity  of  the  process  varies,  and  depends  upon 
the  agent  used,  the  concentration,  the  length  of  time  it  acts,  and  the 

^  Landauer,  "Centralbl.  f.  inn.  Med.,"  April  22,  1899.  Marsh,  "Amer. 
Jour,  of  Med.  Sci.,"  Aug..  1902,  p.  304.  Bickel,  "  Beitr.  z.  klin.  Chir.,"  xliv, 
No.  3.  Phocas,  "Revue  de  Chir.,"  Nov.  10,  1903,  p.  593.  Thomas,  "Lancet," 
Feb.  6,  1904,  p.  361.  Schaffer,  "Virchow's  Arch.,"  1904,  Bd.  177,  p.  i8r.  Re- 
nault and  Sebilleau,  "La  Bulle.  Med.,"  May  25,  1904.  Schwalbe,  "Virchow's 
Arch.,"  1905,  Bd.  175,  p.  65.  Schridde,  "Virchow's  Arch.,"  1905,  Bd.  175,  p.  i. 
Ruckert,  "Virchow's  Arch.,"  1905.  Bd.  175,  p.  16.  Whipham  and  Fagge,  "Lan- 
cet," Jan.  7,  1905,  p.  22.  Sievers,  "Deut.  Zeit.  f.  klin.  Med.,"  Bd.  44,  p.  45. 
Neilson,  "Trans.  Chicago  Path.  Soc,"  Feb.  8,  1904,  p.  73. 


AMMKNTAkV    (ANAL.  69  1 

age  of  the  patient;  young,  tender  mucous  surfaces  are  specially  ])r<)ne 
to  suffer.  Ulceration  usually  follows,  should  the  patient  survive, 
and  contraction  of  the  healed  ulcers  causes  stenosis.  The  catarrhal 
form  may  be  due  to  extension  from  the  continuous  mucosa  above. 
Pseudomembranous  and  gangrenous  inflammations  are  extremely  rare. 
Diphtheria  rarely  involves  the  e.sophagus;  in  Councilman,  Mallory,  and 
Pearce's  220  cases  there  was  membrane  in  the  esophagus  in  12.  In 
alcoholics  large  areas  of  the  esophageal  mucosa  sometimes  exfoliate. 
A  pMci^inonoiis  csophoiiitis  has  been  observed  and  may  be  attended  by 
the  formation  of  definite  abscesses  in  the  submucosa.  The  term  csopha- 
(^cal  pci)tphii;iis^  has  been  applied  to  a  form  of  inflammation  in  which 
definite  vesicles  are  produced,  followed  by  rupture  and  the  production 
of  red,  bleeding,  superficial  ulcers.  The  contiguous  epithelium  is 
grayish  and  often  desquamated.  The  condition  is  commonly  accom- 
panied by  dysphagia,  which  may  be  mistaken  for  stricture.  Langer- 
has  reported  an  instance  of  strc ptothricosis  of  the  esophagus.  Thrush  of 
the  esophagus  has  been  observed,  and  is  usually  secondary  to  a  similar 
process  in  the  mouth.  Peri-esophageal  suppuration  occurs  as  the  result 
of  injury,  diseases  of  adjacent  structures,  and  pvemia. 

Tuberculosis ■'  of  the  esophagus  is  rarely  primary;  it  is  usuallv  due  to 
penetration  of  the  esophageal  wall  by  a  tuberculous  lesion  in  an  adjacent 
lymph-node  or  the  vertebrae.  Ulcerations  following  necrotic  pro- 
cesses due  to  poisons,  and  occasionally  the  open  ulcers  of  syphilis  and 
cancer,  may  be  infected  by  tubercle  bacilli. 

Tertiary  syphilis  sometimes  gives  rise  to  esophageal  ulceration  which, 
on  healing,  produces  a  stricture.  Gummata  may,  by  infiltrating  the 
esophageal  wall,  give  rise  to  obstruction,  but  syphilitic  stenosis  of  the 
esophagus  is  usually  a  sequence  of  cicatrization  of  one  of  the  lesions 
just  mentioned. 

Acti)iomycosis  and  leprosy  rarely  give  rise  to  any  esophageal  mani- 
festation. The  former  may  extend  to  the  gullet  from  lesions  in  the 
mediastinum  or  vertebrae. 

Acquired  stenosis  of  the  esophagus  occurs  in  two  forms: 

1.  Esophagismus  {spasmodic,  hysteric,  or  inorganic  stricture)  arises 
as  (a)  a  manifestation  of  hysteria,  or  as  (6)  a  reflex  phenomenon  due 
to  excessive  irritability.  A  tender  point  in  the  esophagus — a  minute 
abrasion  or  an  ulcer — is  so  sensitive  that  as  soon  as  touched  by  a  bolus 
of  food,  or  by  an  instrument  used  for  e.xploration,  spasm  ensues,  and 
relaxes  only  after  considerable  force  is  continuously  applied  for  some 
time.  When  stenosis  is  due  to  muscle  contraction  near  the  lower  end 
of  the  esophagus,  it  is  called  cardiospasm. 

2.  Organic  stricture  of  the  esophagus  is  a  narrowing  of  the  tube, 
independent  of  muscular  contraction,  and  due  to  disease.  The  nar- 
rowing may  be  a  single  annular  band  or  the  stricture  mav  be  several 
inches  in  length.  There  are  two  places  in  the  esophagus  where  stric- 
ture is  frequent;  the  upper  area  of  election  is  just  behind  the  cricoid 
cartilage;   the  lower,  opposite  the  bifurcation  of  the  trachea. 

'Tamed.  "W'ien.  klin.  Woch.,"  July  21.  1904. 

-  "Zcit.  f.  Hyg.  u.  Infektkrank.,"  1904,  Bd.  47,  H.  3. 

^  Shattock,  "Trans.  Path.  Soc.  of  London,"  1902,  vol.  53.  p.  4^0.  Shrubsall 
and  Mulling.s.  "Trans.  Path.  Soc.  of  London,"  1903,  vol.  54,  p.  84.  Riviere,  "  Brit. 
Med.  Jour.,"  Jan.  24,  1903.  p.  193. 


692  SPECIAL  PATHOLOGY. 

The  causes  may  be  cicatrization  following  injury,  as  that  of  burns, 
scalds,  or  escharotics ;  contraction  and  occlusion  incident  to  the  growth 
of  cancer;  or  syphilis. 

There  is  a  form  of  esophageal  stenosis,  called  simple  stricture  of 
the  esophagus ,  that  does  not  seem  to  be  properly  grouped  with  either 
of  the  foregoing.  There  is  much  doubt  as  to  its  origin,  although  it 
has  been  suggested  that  it  is  a  developmental  defect.  It  is  a  diaphragm- 
like narrowing,  composed  of  an  annular  fold  of  the  mucous  membrane, 
and  usually  situated  near  the  stomach;  it  may  be  caused  by  cicatriza- 
tion of  a  peptic  ulcer,  although  it  is  usually  held  that  cicatricial  tissue 
is  absent. 

Stricture  of  the  esophagus  gives  rise  to  esophageal  obstruction, 
for  which  there  are  many  other  causes:  e.  g.,  foreign  bodies  lodged 
or  w^edged  in  some  part  of  the  tube ;  polypoid  tumors  of  the  esophagus 
(rare) ;  pressure  on  the  esophagus  by  neoplasms  of  surrounding  struc- 
tures, as  mediastinal  sarcoma,  aneurysm  of  aorta,  swollen  lymph- 
nodes,  tuberculosis,  or  other  disease,  of  the  vertebrae.  Pressure  ob- 
struction may  occur  at  any  point;  the  points  of  stricture  obstruction 
have  been  indicated. 

Acquired  dilatation  of  the  esophagus  is  probably  always  secondary 
to  some  other  process.  It  has  been  known  to  follow  spasmodic  stric- 
ture. Organic  stricture,  or  any  form  of  obstruction,  commonly  leads 
to  dilatation  above  the  point  of  narrowing.  The  sac  may  be  fusiform, 
globular,  or,  in  rare  cases,  may  extend  in  one  direction,  forming  a 
diverticulum.  A  form  of  dilatation,  long  held  to  occur  without  ob- 
struction, and  supposed  to  be  due  to  atony  of  the  pharyngeal  muscles, 
has  been  described.  We  are  especially  indebted  to  Mikulicz^  for  the 
demonstration  that  this  type  of  esophageal  widening,  called  atonic 
or  diffuse  dilatation  of  the  esophagus,  is  due  to  contraction  of  the  cir- 
cular fibers  at  or  near  the  gastric  end  of  the  gullet,  a  manifestation 
for  which  he  coined  the  name  cardiospasm.  Rosenheim  and  others 
have  maintained  that  a  congenital  weakness  of  the  esophageal  muscle 
is  an  essential  predisposing  factor.  The  dilated  organ  is  spindle-shaped 
and  may  possess  a  capacity  of  a  liter  or  more.  Esophageal  dilatation 
may  be  associated  with  pyloric  narrowing  and  dilatation  of  the  stomach. 

Esophageal  diverticula^  are  produced  in  a  number  of  ways.  It  is 
possible  that  some  of  the  forms  are  congenital,  or  at  least  the  result 
of  developmental  defects  in  the  musculature  of  the  esophagus.  The 
sacs,  situated  in  the  cervical  region  and  communicating  with  the  esoph- 
agus, are,  in  some  instances  at  least,  branchial  vestiges.  It  is  customary 
to  recognize  pulsion  diverticula,  due  to  pressure  from  within,  and  traction 
diverticula,  resulting  from  contraction  of  adherent  structures  contiguous 
to  the  esophagus.  It  is  also  possible  that  an  esophageal  sac  might 
result  from  cyst  formation  in  the  superficial  glands^  of  the  esophagus. 
Some  additional  explanation  is  needed  for  the  pouches  lined  by  dis- 
tinctly cylindric  epithelium.     Fitz  suggests  that  gullet  pouches  may 

^  "Boston  Med.  and  Surg.  Jour.,"  June  4,  1903,  p.  608;  "  Deut.  med  Woch.," 
1904,  vol.  XXX,  p.  17.  See  also  Tyson,  Martin  and  Evans,  "N.  Y.  Med.  Jour.," 
Oct.  15,  1904,  p.  731. 

*  Starck,  "Die  Divertikel  der  Speiserohre,"  Leipzig,  1903.  Ribbert,  "Vir- 
chow's  Arch.,"  1904,  Bd.  178,  p.  351.  Riebold,  "Virchow's  Arch.,"  1903,  vol. 
173,  p.  395.     Vial,  These  de  Lyon,  1904. 

^  See  Hewlett,  "Jour,  of  Exper.  Med.,"  1901,  vol.  v,  No.  4. 


AI.IMKNTAKV    (ANA  I..  69^ 

result  from  irretjularities  in  the  development  ot  a  Meckel's  diverticulum. 
The  pulsion  diverticulum  is  generally  thought  to  he  a  hernia  of  the  mucosa 
through  a  weakened  or  imperfect  esophageal  musculature.  It  is  usually 
situated  in  the  uj)per  part  of  the  esophagus,  with  which  it  may  com- 
municate by  an  oval,  round,  or  slit-like  opening  in  the  posterior  or 
lateral  wall.  The  sac  may  be  of  almost  any  size,  the  maximum  reported 
length  being  about  12  cm.  The  traction  diverticulum  is  commonly 
the  result  of  an  adhesion  of  the  esophagus  to  an  inflamed  lymph-node, 
which  later,  by  contraction,  gives  rise  to  a  funnel-like  distention  of 
the  wall  of  the  gullet.  The  lesion  is  usually  located  on  the  anterior 
surface  of  the  esophagus  near  the  bifurcation  of  the  trachea.  Riebold 
states  that  such  diverticula  are  ])resent  in  3.5  per  cent,  of  adults  ex- 
amined postmortem.  It  is  possible  that  this  form  may  be  increased 
in  size  by  jtressure  from  within  the  esophagus,  constituting  a  traction- 
pulsion  diverticulum.  The  larger  esophageal  pouches  occurring  at  the 
lower  end  of  the  pharynx  and  similar  structures  arising  in  the  throat 
are  sometimes  called  pharyngoceles. 

Perforation  of  the  esophageal  wall  may  occur  fronr  within  outward 
in  ulceration  processes,  as  cancer,  and  necroses  due  to  lodged  foreign 
bodies,  or  following  other  forms  of  injury.  Extensive  lacerations  by 
exploring  bougies  occasionally  occur.  The  term  esophagomalacia  has 
been  applied  to  conditions  in  which  the  esophageal  wall  is  abnormally 
soft  and  appears  to  rupture  spontaneously.  Spontaneous  rupture'  of 
the  esophagus  is  usually  observed  in  drinking  men,  and  Beneke  believes 
that,  in  some  of  these  cases,  excessive  acidity  on  the  part  of  the  gastric 
juice  and  low  resistance  in  the  tissues  may  determine  an  antemortem 
softening  of  the  gullet.  Postmortem  softening  and  even  rupture  occa- 
sionally occur.  Rupture  may  be  produced  by  injury ;  in  the  case 
reported  by  Whipham  the  man  had  been  thrown  from  a  horse.  The 
esophagus  is  occasionally  penetrated  from  without  by  abscesses  or  tuber- 
culous processes  affecting  the  lymph-nodes  or  vertebrae  Aneurysm  of 
the  aorta  sometimes  ruptures  into  the  esophagus;  malignant  neoplasms 
of  the  larynx  may  give  rise  to  a  communication  between  the  two  tubes. 
Tuberculosis  and  syphilis  of  the  larynx  or  trachea  rarely  penetrate 
the  esophagus. 

Tumors  of  the  esophagus-  are  not  of  frequent  occurrence.  Papil- 
lomata  and  adenomata  are  rarely  encountered.  Fibromata,  myxomata, 
lipomata,  and  myomata  are  occasionally  seen;  such  connective-tissue 
neoplasms  may  be  polypoid  or  sessile  and  sometimes  attain  considerable 
size.  Rokitansky  reported  a  smooth,  lobulated  fibroma  of  the  esoph- 
agus, 17.5  cm.  long  and  6.25  cm.  in  diameter.  SarkisofT  records  an 
instance  of  polypoid  fibroma  of  the  esophagus  that  underwent  necrosis 
and  was  vomited;  the  patient  recovered.  The  gullet  is  rarely  the  seat 
of  sarcoma;  of  the  175  cases  of  sarcoma  of  the  alimentary  tract  col- 
lected by  Comer  and  Fairbank,  but  14  were  esophageal  growths.  Such 
tumors  are  occasionally  polypoid;  all  fonns  of  sarcoma  have  been 
observed.  The  most  frequent  tumor  of  the  esophagus  is  carcinoma, 
and  the  usual  type  is  the  squamous  epithelioma.     Of  the  fifty-four  car- 

'  Whipham.  "Lancet,"  Sept.  12.  1903,  p.  749.  Sec  also  Beneke,  "Deut.  med. 
Woch.,"  1904.  No.  41. 

'Coplin,  'Amer.  Med.."  May  14.  1904,  pp.  773-776.  Comer  and  Fairbank, 
"Practitioner."  June,  1904,  p.  810. 


694 


SPECIAL  PATHOLOGY. 


H    — 


G 


cinomata  of  the  esophagus  included  in  ButHn's  paper,  three  were  scir- 
rhous, one  medullary,  one  colloid,  and  the  remainder  squamous-cell 
epithelioma.     The  tumor  mav  be  polypoid  or  sessile  and  may  or  may 

not  give  rise  to  obstruction, 
although  it  usually  lessens 
the  caliber  of  the  esophagus 
by  contraction,  or,  less 
frequently,  the  mass  is 
;  sufficiently    large    to    ob- 

'  struct.     The    neoplasm    is 

sometimes   restricted  to  a 
•  small    area    and   in    other 

cases  involves  almost  the 
entire  tube.  Occasionally 
more  than  one  growth  is 
present,  in  which  case  the 
uppermost  is  evidently 
older  and  those  below  have 
usually  resulted  from 
metastasis  or  are  grafts. 
Ulceration  is  absent  in 
about  ten  per  cent,  of  the 
cases.  Progressing  necrosis 
may  perforate  the  esopha- 
geal wall  and  penetrate  the 
trachea,  bronchus,  pleura, 
or  pericardium.  Author- 
ities are  not  agreed  as  to 
the  most  frequent  location, 
and  this  probably  indicates 
that  the  tumors  are  fairly 
uniformly  distributed  in 
the  different  parts  of  the 
esophagus.  Of  the  901 
cases  collated  by  Kraus, 
45  involved  more  than  one 
part  of  the  organ;  397 
were  in  the  lower  third, 
302  in  the  middle,  and  158 
in  the  upper  third.  In  some 
cases  malignancy  is  not 
marked;  the  tumor  may 
exist  for  a  number  of  years 
without  manifesting  malig- 
nancy, and  especially  met- 
astasis. Rolleston  states 
that  most  patients  die 
within  one  year  after  the 
appearance  of  symptoms, 
that  carcinoma  of  the  upper  part  of  the  esophagus  is  more  rapidl}^  fatal 
than  when  the  lower  third  is  involved,  and  that  scirrhus  progresses 
less  rapidly  than  the  squamous-cell  variety.     Cvlindric-cell  carcinoma 


F 


A 


-   B 


Fig.  342. — Squamous-cell  Carcinoma  of  the  Esophagus;  Poly- 
poid Type. 

A.  Cardia  of  stomach.  B  to  C.  Cardia  of  esophagus.  C.  Hiatus 
esophagi.  D  to  E.  Area  of  maximum  dilatation  of  the  esopha- 
gus; from  E  upward  the  organ  gradually  diminishes  in  size. 
F.  Wall  of  esophagus.  G  to  H.  F'edicle  of  tumor  by  which  are 
attg,ched  the  projecting  bosses  of  the  new  growth;  at  the  base 
there  appears  to  be  but  slight  infiltration  beneath  the  submucosa, 
although  the  esophageal  wall  is  slighdy  thickened.  The  line 
F,  G,  H,  is  near  the  midline  posteriorly  from  which  the  tumor 
has  arisen. 


ALIMENTARY   CANAL.  695 

of  the  esopha<jus  usually  occurs  at  or  near  the  cardia  and  is  generally 
considered  with  carcinoma  of  the  stomach. 


STOMACH. 

Normal  Structure. — The  external  coat  is  serous;  the  middle  or  mus- 
cle layer  is  composed  of  three  thin  lamella;  of  unstriped  muscle-rtber; 
the  outer  of  these  is  directed  longitudinally,  the  inner  is  arranged 
obliquely,  while  the  circular  fibers  lie  between  the  oblique  and  longitu- 
dinal. The  circular  fibers  are  most  abundant  near  the  pylorus.  The 
muscular  and  serous  layers  are  elastic,  while  the  mucosa  is  less  so,  as 
a  result  of  which,  when  the  organ  is  empty,  it  lies  in  folds  and  elevations. 
The  submucosa  is  abundant  and  loosely  woven.  The  epithelium  of 
the  stomach  is  cylindric,  but  as  it  enters  the  ducts  of  the  glands  it 
becomes  shorter  and  eventually  cuboid.  The  glands  are  of  two  kinds — • 
one  predominating  at  the  cardiac  end.  in  structure  both  simple  and 
branched,  and  containing  columnar,  cuboid,  ovoid,  and  central  cells; 
the  other  glands  are  most  numerous  near  the  pylorus,  are  also  simple 
and  branched,  but  differ  from  the  preceding  in  that  the  neck  or  duct  is 
longer  and  that  the  ovoid  or  parietal  cells  are  absent.  During  life  the 
mucosa  is  pink,  occasionally  red,  but  postmortem  it  assumes  a  much 
darker  hue;  this  is  most  marked  in  the  dependent  portion,  and  may 
be  mistaken  for  evidence  of  disease  or  injury. 

Postmortem  changes  in  the  stomach  result  from  the  action  of  the 
digestive  juices  upon  the  gastric  wall.  In  some  cases  postmortem 
digestion  perforates  the  stomach,  involves  adjacent  tissues,  and  may 
even  penetrate  the  diaphragm.  In  medicolegal  cases  it  is  highly  im- 
portant to  secure  an  early  autopsy,  otherwise,  wounds,  contusions, 
hemorrhages,  and  ruptures  of  the  stomach  can  not  with  certainty  be 
recognized.  It  is  probable  that  during  the  last  hours  of  life,  particu- 
larly when  the  death  agony  is  prolonged,  necrotic  and  other  changes 
in  the  gastric  mucosa  frequently  occur.  An  antemortem  gastromalacia 
has  been  described,  but  it  is  difficult,  if  not  impossible,  to  say  exactly 
how  much  of  this  softening  preceded  death.  In  embolic  and  suppurative 
affections  involving  the  stomach  the  density  of  the  tissue  is  often  greatly 
lessened,  and  small  areas  sometimes  undergo  necrosis,  but  such  condi- 
tions can  not,  with  jiropriety,  be  included  under  the  term  gastromalacia. 

Malposition  and  Malformation  of  the  Stomach. — In  the  situs  in- 
versus and  in  fissural  malformations  of  the  abdominal  wall  or  diaphragm 
the  stomach  may  be  transposed,  or,  in  the  latter  instance,  can  be 
forced  through  the  fissure  and  become  more  or  less  extra -abdominal. 
At  birth  the  stomach  may  be  lower  in  the  abdominal  cavity  than  is 
normal.  Sometimes  the  displacement  is  of  the  stomach  as  a  whole, 
and  is,  therefore,  comparable  to  the  acquired  gastrojUosis  which  will  be 
described  later.  In  other  cases  the  dislocation  is  of  the  pyloric  end 
only,  giving  rise  to  the  so-called  vertical  stomach.  ' 

The  stomach  may  be  abnormally  small,  a  condition  called  micro- 
gastria.  When  the  diminutive  size  is  the  result  of  developmental  con- 
ditions, the  affection  is  called  primitive  microgastria.  Secondary  mi- 
crogastria  may  be  produced  by  cicatricial  contraction  of  the  organ 
following  the  action  of  escharotic  poisons.  In  the  case  reported  by 
Boikofif'  the  stomach  was  no  larger  than  a  watch.  Soupault^  has 
'  "Rovissky  Vratch.'"  June  7.  100;.  '   "La  Bulk-    Mt'-H  ."  June  2S.  IQ02. 


696  SPECIAL   PATHOLOGY 

described  a  form  of  atrophic  retraction  of  the  stomach,  greatly  lessening 
its  capacity  and  thought  to  be  due  to  muscle  spasm,  resembling  the 
spasticity  observed  in  esophagismus.  Gastric  diverticula^  are  occasion- 
ally observed.  They  may  be  of  the  traction  or  pulsion  types,  and 
resemble  similar  structures  occurring  in  the  esophagus;  in  the  stomach 
diverticuli  are  infrequent  and  the  traction  form  is  exceedingly  rare. 
Atresia  and  stenosis,  of  the  cardia  or  pylorus,  are  occasionally  observed. 
Under  the  name  of  congenital  hypertrophic  stenosis-  of  the  pylorus  has 
been  described  a  form  of  pyloric  obstruction  in  which  there  is  a  not- 
able increase  in  the  muscle  layer,  particularly  the  circular  fibers,  and  a 
varying  degree  of  hyperplasia  of  the  connective  tissue  in  the  submucosa. 
In  the  case  reported  by  Thomson  there  was  an  increase  in  the  submucous 
lymphoid  tissue.  There  has  been  considerable  discussion  as  to  whether 
the  stenosis  is  spastic  or  hyperplastic.  Thomson  and  a  number  of  ob- 
servers hold  that  the  spasm  is  primary  and  the  hyperplasia  secondary. 
Cautley  believes  that  the  first  change  is  a  hyperplasia  or  notable  increase 
in  muscle,  and  that  the  spasm  is  secondary.  At  autopsy  or  operation 
the  pylorus  is  found  greatly  thickened  and  the  lumen  so  narrowed  that 
it  may  be  impossible  to  force  the  gastric  contents  through  the  opening. 
When  inspected  from  the  duodenal  side  the  pylorus  often  projects  into 
the  duodenum,  and  resembles  the  cervix  uteri.  Sometimes  a  longitudi- 
nal fold  of  the  gastric  mucosa  occupies  the  opening  in  such  a  way  as 
to  indicate  that  the  lumen  has  been  greatly  diminished  after  the  mucous 
membrane  developed.  Microscopic  examination  discloses  an  enormous 
broadening  in  the  circular  muscular  layer  with  little  if  any  increase  in 
the  longitudinal  fibers.  In  some  cases  there  is  an  excess  of  fibrous  tissue 
interspersed  in  the  muscle.  The  stomach  is  usually  dilated  and  in  some 
cases  the  gastric  walls  are  thickened. 

Hour-glass  stomach,''  also  called  bifid  stomach,  and  trifid  stomach, 
or  multilocular  stomach,  are  conditions  due  to  abnormal  septa  or  con- 
strictions dividing  the  gastric  cavity  into  a  number  of  smaller  sacs. 
The  most  common  of  these  is  the  hour-glass  stomach.  It  is  usually 
stated  that  this  condition  may  be  congenital,  but  Moynihan  does  not 
believe  that  there  is  a  single  specimen,  or  an  authentic  record,  which 
establishes  the  developmental  origin  of  the  affection.  He  holds  that 
all  such  organs  are  the  result  of  cicatricial  contraction  of  gastric  ulcers, 
cancers,  or  perigastric  adhesions.  I  have  on  a  number  of  occasions, 
at  autopsy  observed  a  circular  constriction  dividing  the  stomach  into 
two  cavities,  and  giving  rise  to  all  the  external  appearances  of  an  hour- 
glass organ,  but,  on  closer  examination,  found  that  protracted  insuffla- 
tion caused  the  constriction  to  disappear.  Dwight  remarks  that  such 
ring-like  contractions  may  be  physiologic. 

Dilated  stomachs  are  abnormally  capacious,  but  the  increased  size 
is  due  to  relaxation  of  the  muscle.  The  term  megastria  or  megalo- 
gastria  is  applied  to  unusually  large  organs  which,  aside  from  their 
great  size,  show  no  abnormality.     It  is  said  that  the  condition  is  occa- 

'  Ferguson,  "Glasgow  Med.  Jour.."  March,  1898.  Hirsch,  "Virchow's  Arch.." 
1903,  Bd.  174,  p.  576. 

'^  Mo^-nihan.  "Med.  News."  Oct.  24,  1903.  Clogg,  "Practitioner,"  Nov.,  1904, 
p.  624.     Scudder,  "Boston  Med.  and  Surg.  Jour.,"  April  27,  1905,  p.  494. 

^Dwight,  "Amer.  Jour,  of  Med.  Sci.,"  Oct.,  1903,  p.  581.  Moynihan.  "Brit. 
Med.  Jour.,"  Feb.  20.  1904.  p.  413. 


A 1. 1  .\  I  li  N  T  A  R  Y   C  A  X  A  L 


697 


sionally  congenital,  and  that  it  is  observed  in  those  who  hal)ituaily  C(jn- 
sume  a  diet  poor  in  nutrients,  such  as  the  dirt-  and  root-eaters. 

Acquired  Malpositions  of  the  Stomach. — Anterior  displacements 
due  to  defects  ot  the  aI)(K)niinal  wall  have  been  referred  to.  Diaphrag- 
matic hernia,  whether  congenital  or  acijuired,  may  |jermit  a  large  part 
of  the  cardia  to  enter  the  thoracic  cavity.  Occasionally  the  hernia  is 
through  a  dilated  esophageal  opening.  Of  the  twenty-four  congenital 
cases  collected  by  Knaggs,^  fifteen  were  in  individuals  between  six  weeks 
and  sixty  years  of  age.  In  nine  the  stomach  w^as  the  only  viscus  that 
entered  the  sac.  A  number  of  cases  of  volvulus  of  the  stomach^  have 
been  reported.  It  may  or  may  not  be  associated  with  volvulus  of 
the  colon.  In  two  of  the  recorded  cases  the  torsion  afTe(te<l  the  pyloric 
sac  of  hour-glass  stomachs.  Gastroptosis '  or  descensus  ventriculi  is 
frequently  nothing  more  than  a  part  of  splanchnoptosis,  and  rarely,  if 
ever,  occurs  alone.  Enlarged  or 
dilated    stomachs    are    particu-  4 

larly  prone  to  downward  dis- 
placement, but  Treves  and  other 
authorities  are  agreed  that 
gastroptosis  may  occur  inde- 
pendently of  any  disease  of  the 
viscus.  The  essential  features 
underlying  the  causes  of  pro- 
lapsed stomach  are  similar  to 
those  given  for  si>lanchnoptosis. 

The  bacteria  of  the  stomach,^ 
in  health,  are  few^  and  of  little 
importance.  The  bactericidal 
action  of  the  gastric  juice,  under 
normal  conditions,  exerts  a  dis- 
tinct protective  influence,  and 
is  destructive  to  many  bacteria 
that  otherwise  might  cause  in- 
fection in  the  intestine.  In 
diseased  stomachs,  and  particu- 
larly in  dilated  organs,  w^ith  or 
w^ithout  pyloric  stenosis  but  per- 
mitting food  stasis,  bacteria  are 
particularly  numerous.     It  was 

at  one  time  hoped  that  the  diagnosis  of  cancer,  and  possibly  of  some 
other  gastric  conditions,  might  be  made  by  a  bacteriologic  examination 
of  the  gastric  contents.  Such  expectations  have  not  been  fulfilled.  At 
most,  the  bacteria  indicate  the  reaction  of  the  gastric  secretion  and  rarely 
have  any  specific  value  in  diagnosis.  In  the  presence  of  hydrochloric 
acid,  yeasts,  molds,  and  sarcinae  are  the  prevailing  flora  of  the  stomach. 


—  C 


I'lo.  343 


Stomach;  Hour-glass  CoNTR.\cnoN  Secon- 
dary TO  Gastric  Ulcer. 
Lower  end  of  esophagus,  fi.  The  contracted  and  dis- 
torted part  of  the  lesser  curvature,  enclosed  between 
the  two  ends 'of  the  leader,  marks  the  ulccr-boarinB 
area.  The  line  most  dLstant  from  the  letter  B  leads 
to  the  area  of  advanced  cicatricial  contraction.  C. 
Cardiac  complement,  also  calletl  cardiac  sac.  D.  Pylorii 
complement,  also  called  pyloric  sac. 


"  Lancet, 
Spivak, 


Aug.  6.  1004. 


Pendl.  'Wien.  klin.  Woch.," 


Amer.  Med.,"  Oct.  31,  1903,  p.  700. 
April  28,  1904.  p.  476.     Dujon.  "Gaz.  M^d.  de  Paris."  March  28.  1003.  p.  109. 

'  See  references  to  Splanchnoptosis  on  p.  431.  also  Steele  and  Francine,  "Jour. 
Amer.  Med.  Assoc."  Nov.  S,  1902,  and  Francine.  "Univ.  of  Penna.  Med.  Bull.," 
Jan..  1903. 

*  See  Coyon,  "Flore  microbienne  de  I'estomao."  These  de  Paris.  1900.  Also 
Palier.  "Med.  Record,"  Nov.  19,  1904,  p.  801. 


698  SPECIAL  PATHOLOGY. 

Bacilli,  spirilli,  and  cocci  are  usually  more  abundant  when  hydrochloric 
acid  is  absent.  An  organism  often  present  is  the  Oppler-Boas  bacillus; 
it  is  rod-shaped,  0.2  /'  to  0.5  ,«  wide,  and  about  6  «  long;  bent  forms 
are  frequent;  the  bacillus  stains  by  Gram's  method.  It  is  a  facultative 
anaerobe  and  non-motile.  Kaufmann  and  Schlesinger  found  it  in  nine- 
teen of  twenty  cases  of  cancer  of  the  stomach.  Palier  says  that  it  in- 
dicates deficiency  in  hydrochloric  acid  and  nothing  more.  Infusoria^ 
are  sometimes  found  in  the  stomach. 

Foreign  Bodies  in  the  Stomach.- — Various  articles  may  be  accident- 
ally swallowed,  especially  by  children;  in  other  instances  foreign  bodies 
are  intentionally  introduced,  particularly  by  persons  attempting  suicide 
and  by  the  insane,  or  by  individuals  who  make  a  living  by  exhibiting 
an  ability  to  ingest  all  sorts  of  substances.  Of  the  90  cases  collected 
by  Friedenwald  and  Rosenthal,  in  68  a  single  foreign  body  was  present 
and  in  22  they  were  multiple.  In  the  case  reported  by  Halsted  there 
were  208  foreign  bodies  in  the  stomach;  the  articles  .present  included 
594  cm.  (about  6  yards)  of  watch-chain  and  dog-chain,  99  nails,  88  pieces 
of  scrap-iron  of  one  kind  or  another,  and  74  gm.  of  glass.  In  one  re- 
ported case  the  stomach  contained  5500  gm.  (11  pounds  9  ounces)  of 
foreign  material.  Hair  balls  and  string  balls  result  from  swallowing 
hair  or  pieces  of  string.  Masses  produced  in  this  manner  may  weigh 
2  kilos  or  more  and  extend  into  the  esophagus  and  duodenum.  When 
small,  thev  are  usually  in  the  pyloric  area,  but  later  mold  themselves 
to  the  shape  of  the  stomach.  Ulcers  of  the  gastric  mucosa,  pylorus, 
or  upper  duodenum  are  not  infrequently  present.  Solid  bodies  fre- 
quentlv  perforate,  but  often  perigastric  adhesions  prevent  escape  into 
the  peritoneum  and  the  disastrous  results  of  extensive  infection.  Gas- 
troliths  are  extremely  infrequent,  and  rarely  weigh  more  than  100  gm., 
although  in  the  case'  reported  by  Tidemand  the  weight  was  1500  gm. 
When  these  or  other  foreign  bodies  remain  long  in  the  stomach,  papil- 
lomata  are  sometimes  produced. 

Hyperemia  of  the  stomach  is  a  physiologic  process  during  digestion, 
and  also  occurs  in  the  initial  stage  of  acute  inflammations.  The  intense 
distention  of  the  blood-vessels  of  the  organ  and  other  abdominal  viscera 
during  the  chill  stage  of  the  malaria  paroxysm  has  been  variously 
placed,  some  regarding  it  as  a  visceral  hyperemia,  and  others  believing 
that  the  increased  amount  of  blood  in  the  viscera  is  the  result  of  venous 
accumulation.     It  is  not  improbable  that  both  factors  are  operative. 

Congestion  of  the  stomach  is  often  marked  in  cardiac  and  pulmonary 
diseases  associated  with  venous  stasis,  and  as  a  result  of  cirrhosis  of 
the  liver;  congestion  may  precede,  accompany,  or  follow  gastroptosis. 
The  appearances  produced  by  or  accompanying  intense  congestion  have 
been  mistaken  for  the  lesions  resulting  from  the  action  of  destructive 
or  escharotic  poisons. 

Gastrorrhagia,  or  hemorrhage  into  the  stomach,  may  be  acute  or 

iRosenfeld,  "Deut.  med.  Woch.,"  30  Jahrg.  No.  47^  P-  i7i7-  Zabel,  "Wien. 
klin.  Woch.."  Sept.  22,  IQ04.  p.  1007.  . 

2  Halsted.  •' Contributions  to  the  Science  of  Medicine."  Dedicated  by  his  Pupils 
to  William  Henrv  Welch,  1900.  p.  1048.  Friedenwald  and  Rosenthal,  "N.  Y. 
Med.  Jour.,"  Julv'iS.  1903,  p.  no.  Cathelin,  "  Bulle.  et  Mem.  de  la  Soc.  Anat.  de 
Paris,"  Jan.,  1902.  Fenwick,  "  Brit.  Med.  Jour.,"  Nov.  29,  1902,  p.  1696.  Mallins, 
"Lancet,"  June  6,  1903,  p.  1592.  Ranzi,  "Wien.  klin.  Woch.,"  Dec.  15,  1904, 
p.  1341. 


AI.IMKNTARY    CANAL.  6qo 

chronic.  The  lonncr  may  be  fulminating,  in  which  case  death  some- 
times occurs,  unattended  by  hematemesis  or  mclcna,  although  usually 
some  blood  is  vomited.  In  acute  recurring  gastrorrhagia  the  hemor- 
rhages are  repeateil  at  intervals  which  may  be  brief  or  long.  In  chronic 
gastrorrhagia  a  small  amount  of  blood  is  continuously  present;  in  this 
form  the  blood  may  not  be  perceptible,  but  can  be  detected  by  ap- 
propriate chemic  tests;  Boas'  calls  this  occult  gastric  hemorrhage.  In 
submucous,  parenchymatous,  or  interstitial  ga.stric  hemorrhage,  the 
blood  escapes  into  the  submucosa,  muscular  wall  of  the  stomach,  or 
subserosa.  Blood  in  the  cavity  of  the  stomach  usually  gives  rise  to 
vomiting;  when  the  vomited  matter  contains  recognizable  blood,  the 
condition  is  called  hematemesis.'  The  altered  blood  is  also  voided  in 
the  stools,  a  condition  termed  melena. 

Hematemesis  may  be  due  to  increased  tension  within  the  portal 
vein  or  its  branches,  produced  by  cirrhosis  of  the  liver,  cardiac  disease, 
or  pulmonary  lesions  accompanied  by  venous  stasis.  Hemorrhage  into 
the  stomach  also  occurs  in  the  intense  hyperemia  of  acute  inflammation 
involving  the  gastric  mucosa,  and  less  frequently  in  chronic  gastritis. 
It  is  one  of  the  most  frequent  symptoms  of  gastric  ulcer  and  gastric 
cancer.  The  fulminating  form  is  dae  to  lesions  involving  larger  arterial 
or  venous  branches  in  the  stomach,  or  rupture  of  aneurysms  in  the 
gastric  wall  or  of  the  splenic  artery  or  aorta.  Ruptured  varicose  veins 
may  also  cause  gastrorrhagia.  The  hemorrhages  produced  by  retching, 
hanging,  strangulation,  and  epileptic  seizures  are  rarely  severe.  Blows 
on  the  abdominal  wall,  and  penetrating  wounds  of,  or  foreign  bodies  in. 
the  stomach,  may  injure  the  mucosa  and  induce  bleeding.  Gastric 
hemorrhage  may  be  vicarious.  Blood  may  be  vomited  in  a  number 
of  constitutional  alTections,  among  which  should  be  mentioned  yellow 
fever,  malaria,  purpura,  smallpox,  plague,  and  pyemia  and  septicemia, 
especiallv  when  embolic  processes  involve  the  gastric  wall.  Thrombosis 
of  the  gastric  vessels,  volvulus  of  the  stomach,  and  hernias  in  which 
part  of  the  gastric  wall  is  strangulated,  may  produce  bleeding,  and  in 
some  of  these  conditions  vomiting  is  possible.  Gastric  hemorrhage 
sometimes  follows  operations,  particularly  those  involving  the  appendix 
and  other  abdominal  structures,  even  when  the  stomach  is  believed  to 
be  uninjured.  The  bleeding  resulting  from  fissures,  superficial  excoria- 
tions or  erosions,  and  that  accompanying  infectious  diseases,  may  be 
from  a  mucosa  which,  at  operation  or  autopsy,  shows  no  macroscopic 
lesions.  Vomited  blood  may  not  have  originated  from  gastrorrhagia. 
In  hemoptysis,  epistaxis,  esophageal  hemorrhage,  and  bleeding  from 
other  causes,  the  blood  may  be  swallowed,  and  later  a]ipear  in  the 
vomit;  nursing  infants  may  suck  blood  from  the  mother's  breast. 

Vomited  blood  is  usually  clotted  or  contains  coagula,  is  not  red  or 
frothv.  as  in  hemoptysis,  and  the  reaction  is  commonly  acid.  As  a 
result  of  partial  digestion  it  may  be  black,  greenish,  or  granular,  some- 
times resembling  coffee-grounds.  When  the  hemorrhage  is  fulminating 
and  the  quantity  of  blood  large,  it  does  not  remain  in  the  stomach 
sufhcientlv  long  to  be  affected  by  the  gastric  juice  and  hence  shows 
none   of  the   changes  just  mentioned.^     Small   depleting   hemorrhages 

'  "Deut.  med.  Woch.,"  Leipzig.  Mav  i6.  iqoi 

'Janowski.  -Zeit.  f.  klin.  Med.."' Bd.  46.  Nos.  1-4  Moynihan,  'Boston 
Med.  and  Surg.  Jour.,"  June  4.   1903.  p.  611.     Connell,  'Med.  News,"  Oct.  29. 

1904.  p.  8^3- 


yoo  SPECIAL  PATHOLOGY. 

may  give  rise  to  marked  anemia;     or  anemias,  such  as  leukemia  and 
pernicious  anemia,  occasionally  produce  gastric  bleeding. 

Degenerations  and  infiltrations  of  the  gastric  mucosa,  unattended 
bv  inflammation,  are  observed  in  profound  anemias  and  accompany 
various  toxemias.  Hayem^  describes  what  he  terms  degenerative  gas- 
tritis, occurring  in  such  infectious  diseases  as  pneumonia,  diphtheria, 
and  in  typhoid,  and  in  severe  icterus.  Similar  lesions  have  been  pro- 
duced in  animals  by  the  subcutaneous  injection  of  bacterial  toxins. 
GraQular  and  fatty  degenerations  of  the  epithelium  occur,  desquamation 
is  rarely  marked,  and  the  hyperemia  of  acute  inflammatory  conditions 
is  usually  absent.  In  the  degenerative  changes  accompanying  anemia, 
particularly  of  the  pernicious  type,  chronic  Bright's  disease,  tubercu- 
losis, and  other  debilitating  conditions,  the  epithelium  shows  fatty  and 
granular  change  and  the  mucosa  is  perceptibly  thinned  without  any 
important  increase  in  the  connective  tissue. 

B 


D  . 


Fig.  344. — Stomach,  Chronic  Catarrhal  Gastritis  with  Erosions.     (Two-thirds  natural  size.) 
A .  Small  superficial  incomplete  erosion.     B.  Small  erosions  slightly  deeper  than  that  shown  at  ^4 .     C,  C.  Larger 
and  deeper  sharply  circumscribed  erosions.     D.  Large  erosions  the  upper  pair  of  which  are  sharply  limited 
in  part  only;  one  margin  gradually  merges  with  the  contiguous  mucosa. 

■^'Gastritis  is  a  term  applied  to  all  the  inflammations  involving  the 
stomach,  not  including,  however,  the  overlying  serosa.  When  the 
latter  structure  is  affected,  the  condition  is  called  perigastritis  or  peri- 
gastric peritonitis.  Perigastritis  does  not  include  inflammation  of  the 
peritoneum  resulting  from  infection  arising  at  some  distance  from,  and 
extending  to,  the  stomach. 

Acute  catarrhal  gastritis,  or  acute  gastric  catarrh,  is  usually  due 
to  ingested  poisons,  among  which  should  be  included  toxic  substances, 
and  other  irritants  present  in  the  food;  overeating  or  excessive  indul- 
gence in  alcohol  are  also  causes.  There  may  be  some  doubt  as  to 
whether  fermentative  changes  occur  in  a  stomach  the  mucosa  of  which 
is  normal,  but  all  are  agreed  that  fermentation  irritates  the  gastric 
mucosa   and   may   produce   inflammation,   or  intensify   a   pre-existing 

1  "Soc.  Med.  des  Hop.,"  Feb.,  1005;    "La  Sem.  Med.,"  March  i,  1905,  p.  103. 


ALIMENTARY   CANAL.  7OI 

gastritis.  The  affected  mucosa  is  usually  red  and  swollen  and  often 
coated  with  tenacious  mucus.  The  submucosa  frequently  contains  a  small 
number  of  leukocytes,  the  epithelium  is  desquamating,  and  the  vessels 
often  distended.  If  the  irritation  has  been  intense,  or  the  mucosa 
])revi()usl\-  weakened.  sui)crficial  erosions  are  occasioiiallv  present. 

Chronic  gastritis,  also  calleil  chronic  gastric  catarrh  and  chronic 
dyspepsia,  may  follow  a  number  of  acute  attacks  or  arise  insidiously; 
it  usually  results  from  prolonged  or  frequent  irritation,  and  is  espe- 
cially prevalent  in  persons  addicted  to  intemperate  eating  or  alcoholic 
excesses.  The  habitual  consumption  of  highly  seasoned  food,  sweets, 
and  pastry  may  give  rise  to  chronic  gastric  catarrh.  Motor  insuffi- 
ciency and  pyloric  obstruction,  by  inducing  food  stasis,  facilitate  fer- 
mentation, which  in  turn  irritates  the  mucosa  and  leads  to  chronic 
inflammation.  Ulcer,  cancer,  and  other  morbid  processes  restricted  to 
some  part  of  the  stomach,  are  usually  accompanied  by  chronic  gas- 

D  •    D 


F 


w^m»:pJ .^MmiM>, 


-.-»•'. 


•^M'^M 


ws^^0''        --^m^  ■^■\.  i^ 


Fic.  345. — Stomach,  Chronic  Catakrhal  Gastritts  with  Erosions;  Vertical  Section  through  an 
Erosion.     (B  and  L.  }  in.;   Zeiss  projection  oc.  A.) 

A .  Surface  of  mucosa.  B.  Base  of  mucosa.  C.  Muscularis  mucosa?.  D  to  D.  Limits  of  erosion.  E.  Line 
ptassing  throuuh  center  of  erosion  to  mass  of  shrunken,  granular,  and  desquamated  epithelium  l>ing  in  a  gland 
space.  F.  .Mtcrcd  gland  epithelium.  The  muco<ia  throughout  is  more  or  less  narrowe<l  and  structurally 
altered.  The  number  of  gland  tubules  is  greatly  diminished  at  all  points.  The  glandular  epithelium  is  gran- 
ular and  wasted  and  has  retracted  from  the  sustaining  connective  tissue;  the  types  of  gland  cells  that  usually 
can  readily  be  differentiated  are  no  longer  distinguishable.  The  intertubular  spaces  are  universally  infiltrateil 
by  Ijinphoid  cells,  some  of  which  are  present  in  the  interstitial  tissue. 

tritis.  Continued  congestion  of  the  organ,  and  constitutional  affections, 
particularly  Bright's  disease,  predispose  to  the  chronic  lesion  or  intensify 
it  when  developed.  The  color  of  the  affected  membrane  depends  upon 
the  extent  of  the  associated  hyperemia;  in  the  earlier  stages  of  the 
process  the  mucosa  is  swollen,  gray,  and  usually  smooth.  Later  the 
swelling  and  thickening  are  less  intense.  Sometimes  the  thickenint'; 
gives  rise  to  irregular  folds  or  distinct  projections  (mammillated  stom- 
ach I,  and  occasionally  the  elevated  mucosa  is  wart-like  or  polypoid  (gas- 
tritis polyposa).  The  projecting  masses  of  edematous  and  intiltrated 
tissue  sometimes  undergo  necrosis  and  may  be  vomited.  During  this 
period  a  notable  hyperplasia  of  the  submucosa  and  lymphoid  tissues 
commonly  occurs.  At  this  time  a  microscopic  examination  reveals 
conspicuous  mononuclear  infiltration  in  the  submucous  structures  and 
between  the  gastric  tubules;  the  epithelium  is  desquamating,  usually 
immature,   and   the  distinction  between   the   different  cells  lining  the 


702  SPECIAL  PATHOLOGY. 

tubules  is  no  longer  present.  The  epithelial  cells  are  commonly  loaded 
with  mucin,  in  a  way  justifying  the  statement  that  mucoid  degeneration 
accompanies  the  process.  In  other  cases  the  mucosa  is  found  thinned," 
distinctly  fibroid,  abnormally  smooth  and  dense.  The  gastric  tubules 
are  wasted,  the  epithelium  scanty,  and  a  notable  increase  of  the  con- 
nective tissue  is  present  between  the  tubules  and  in  the  submucosa. 
It  is  not  certain  that  this  form  has  been  preceded  by  distinct  hyper- 
trophy, as  proliferation  of  the  connective  tissue  and  contraction  may 
be  sufficiently  rapid  to  prevent  any  manifest  thickening.  In  this  form 
the  affection  is  called  fibroid  or  atrophic  gastritis  and  the  condition  is 
identical  with  the  phthisis  mucosae  of  other  writers.  The  alterations  in 
gastric  secretion  are  usually  proportionate  to  the  extent  of  the  lesion. 

Pseudomembranous,  fibrinous,  or  croupous  gastritis^  is  exceedingly 
rare.  False  membrane  formation  on  the  gastric  mucosa  sometimes 
accompanies  infectious  diseases,  but  is  rare,  even  in  diphtheria.  Thom- 
son records  an  instance  in  which  a  complete  cast  of  the  stomach  was 
vomited. 

Phlegmonous  gastritis,-  or  linitis  suppurativa,  may  be  diffuse  or 
circumscribed,  primary  or  secondary.  It  is  due  to  infection  by  pyogenic 
bacteria  which  may  enter  the  submucosa  from  the  blood-stream,  from 
the  surface,  or  through  some  pre-existing  lesion,  such  as  an  erosion, 
o-astric  ulcer,  or  cancer.  The  circumscribed  form  usually  involves  the 
pyloric  area.  It  may  give  rise  to  a  single  abscess  or  the  suppurative 
foci  may  be  small  and  multiple.  The  abscess  sometimes  ruptures  into 
the  stomach,  and  again  it  penetrates  the  peritoneum.  The  diffuse  form 
may  involve  the  whole  of  the  stomach  or  be  restricted  to  one  area, 
usually  in  the  pyloric  end  of  the  organ.  The  formation  of  distinct 
cavities  containing  pus  does  not  occur;  the  submucosa  and  interstitial 
tissue  are  infiltrated  by  polymorphonuclear  leukocytes,  the  epithelium 
desquamating  or  in  part  necrotic,  and  the  overlying  serosa  sometimes 
inflamed.  About  eighty-five  cases  have  been  reported;  most  of  the 
patients  are  alcoholics.  The  condition  sometimes  complicates  puerperal 
and  other  forms  of  sepsis. 

Plastic  linitis,^  hyperplastic  interstitial  gastritis,  sclerosis  of  the 
stomach,  and  gastric  cirrhosis,  are  names  applied  to  a  condition  in 
which  there  is  an  enormous  increase  in  the  connective  tissue  of  the 
gastric  wall.  A  similar  appearance  is  produced  by  carcinomatous 
infiltration  of  the  stomach  with  the  production  of  a  large  amount  of 
fibrous  tissue.  In  either  case  the  wall  of  the  organ  is  thickened  and 
indurated  (leather-bottle  stomach).  The  fibrous  tissue  increase  is  not 
always  distributed  in  the  same  structures  nor  uniform  throughout  the 
organ;  it  is  usually  abundant  in  the  submucosa  and  sometimes  dense 
plaques  are  formed  beneath  the  serosa.  Histologically,  it  is  cellular 
in  the  earlier  stages  and  particularly  abundant  about  the  blood-vessels. 

Perigastritis  may  be  acute  or  chronic ;  the  former  may  be  suppurative 
or  adhesive;  the  chronic  type  is  usually  productive.  When  an  ulcer 
or  other  lesion,  affecting  the  gastric  wall,  slowly  approaches  the  surface 

1  Susswein.  "Wien.  klin.  Woch.,"  1902,  No.  6.  Foulerton,  "Lancet,"  April 
12,  1902.      Griinbaum,  "Lancet,"  Aug.  2,  1902. 

^  Klein eberger,  "Miinch.  med.  Woch.,"  Aug.  4,  1903,  p.  133S.  Moynihan, 
"Med.  Chronicle,"  Nov.,  1903. 

^  Hoche,  "Revue  de  Med.,"  Nov.  and  Dec,  1903. 


ALIMKNT.VkV    CANAI..  703 

of  the  organ  and  is  without  virulent  infection,  an  adhesion  to  some 
contijjuous  structure  is  produced.  In  this  way  perigastric  adhesions 
may  tirmlv  fix.  the  wall  of  the  stomach  to  some  adjacent  viscus  or  the 
abdominal  parietes  (adhesive  form  of  perigastritis).  If  the  lesion  be 
attended  bv  pvogenic  infection,  the  margin  of  the  area  may  be  walled 
by  fibrin,  which  later,  in  favorable  cases,  organizes  and  limits  the  sup- 
purative process.  A  distinct  collection  of  pus  is  formed  (perigastric 
abscess),  or,  in  the  absence  of  adequate  adhesions,  the  infection  extends 
into  the  peritoneum  and  causes  general  peritonitis.  An  extending  or 
necrosing  lesion  within  the  stomach  may,  by  the  formation  of  adhesions, 
penetrate  a  contiguous  organ  without  giving  rise  to  general  peritonitis; 
in  this  wav  fistulae  between  the  stomach  and  colon  are  produced,  and 
in  a  similar  manner  gastric  ulcer  or  carcinoma  may  extend  into  the 
spleen  and  liver  and  through  the  diaphragm.  Chronic  productive  peri- 
gastritis is  identical  with  the  localized  hy^^erplastic  serositis  described 
on  pau'C  47 .^ 

Tuberculosis  of  the  stomach'  is  rare.  Terrannini  has  shown  that 
the  gastric  juice  is  not  destructive  to  tubercle  bacilli,  but  the  experi- 
ments of  Arloing  indicate  that  the  mucosa  is  resistant,  and  rarely,  if 
ever,  infected  from  the  surface.  Arloing  believes  that  infection  by 
the  blood-stream  readily  occurs.  A  simple  ulcer  may  become  tubercu- 
lous. Of  the  147  tuberculous  ulcers  collected  by  Arloing,  perforation 
occurred  in  13.  The  edges  of  the  ulcer  are  undermined  and  the  base 
commonlv  granular;  neither  bacilli  nor  tubercles  are  abundant.  The 
case  reported  by  Van  Wart  is  the  only  instance  of  which  I  know,  where 
the  lesion  was  not  associated  with  evidence  of  tuberculosis  in  other 
organs.  The  nodule  was  covered  by  the  intact  mucosa  and  contained 
caseous  material  and  tubercle  bacilli;  several  small  ulcers  were  also 
present.  Simmonds  in  2000  autopsies  on  tuberculous  subjects  found 
secondarv  gastric  ulcers  in  S.     Occasionally  hematemesis  is  produced. 

Syphilis  of  the  stomach-  occurs  in  both  the  acquired  and  hereditary 
forms  of  the  disease.  The  gastric  manifestations  may  consist  of  gum- 
mata  which  may  be  multiple,  syj)hilitic  ulcer  of  the  stomach,  and  chronic 
inflammations  of  the  mucosa.  Dieulafoy  also  mentions  hemorrhagic 
erosions,  ecchymoses,  and  cicatricial  contraction,  the  latter  resulting 
from  healed  lesions.  The  gummata  may  soften  and  give  rise  to  ulcers 
which  occasionally  perforate;  ulcerative  lesions  may  also  result  from 
obliterative  changes  in  the  blood-vessels  of  the  gastric  mucosa.  Hem- 
meter  and  Stokes  have  reported  a  case  of  hypertrophic  gastritis  of 
svphilitic  origin.  Einhorn  states  that  syphilis  of  the  stomach  may  cause 
pvloric  stenosis. 

Gastric  ulcer,'  peptic  ulceration,  simple  ulcer  of  the  stomach,  and 

'Arloing.  'Les  ulcerations  tuberciileuscs  de  restomac."  Paris,  iqo?.  Ter- 
rannini, "  Rif .  Med,"  June  24,  190.?.  Van  Wart.  "Johns  Hopkins  Hospital 
Bull.."  Sept.,  1903,  p.  235. 

'  E)inhom,  "Jour.  Amer.  Med.  Assoc."  Oct.  2^.  1902.  p.  io>i.  Gross,  Munch, 
med.  Woch.,"  Jan.  27,  1903.  p.  157.  Lafleur.  "Montreal  Med.  Jour.."  July.  1903. 
Havem,  "La  Presse  Med."  Feb.  18.  1905.  p.  105. 

'*The  literature  of  jjastric  ulcer  is  too  voluminous  to  be  incorporated  in  this 
volume.  See  Nothnauel's  Encyclopedia  of  Practical  Medicine.  American  edition, 
volume  on  "Diseases  of  the  Stomach."  1904.  p.  >4.?-  Also  W'eilunj:  and  EtTendi, 
"Deut.  med.  Woch.,"  1904.  No.  53.  Dumeny,  Those  de  Paris.  1903.  F.  and  G. 
Gross.  '"Revue  de  Chir  ."  Feb.  10,  1904.  p.  137  Howard.  •'Med.  News,"  Oct. 
8,  1904,  p.  673.     Moynihan.  ""Lancet,  "  Feb.  11,  1905.  : 


704  SPECIAL  PATHOLOGY. 

round  ulcer  are  names  given  to  an  affection  most  common  in  the  stomach, 
but  also  involving  the  duodenum,  and  less  frequently  the  lower  part  of 
the  esophagus;  Qu^nu  and  Duval  believe  that  a  similar  ulcer  occurs 
in  the  colon. 

Welch  observes  that  we  know  little  more  of  the  etiology  of  gastric 
ulcer  than  we  did  twenty  years  ago,  at  which  time  his  exhaustive  article 
on  the  subject  appeared.  The  characteristic  lesion  seems  inseparably 
connected  with  the  presence  of  gastric  juice;  this  is  shown  by  the 
ordinary  location  of  the  affection  and  by  the  fact  that  peptic  ulcers 
occur  in  the  jejunum  after  gastroenterostomy;  according  to  Mikulicz, 
there  are  fifteen  recorded  instances  of  ulceration  in  the  jejunum  fol- 
lowing anastomoses  between  the  stomach  and  this  part  of  the  intestine. 
Apparently  some  local  nutritional  disturbance  renders  the  mucosa 
susceptible  to  the  digestive  action  of  the  gastric  juice.  The  exact 
character  of  this  deteriorating  influence  is  not  known.  It  has  been 
suggested  that  the  mucosa  may  be  altered  by  embolism,  thrombosis, 
obliterative  endarteritis,  vascular  spasm,  spasm  of  the  gastric  wall,  and 
injury,  and  that  when  any  one,  or  a  combination  of  these  conditions, 
deprives  the  surface  of  its  proper  nutrition,  the  gastric  juice  digests 
the  affected  area  and  an  ulcer  results.  MacCallum^  has  recently  re- 
peated the  experiments  of  former  observers  on  the  production  of  gastric 
ulcer  bv  embolism,  and  has  shown  that  it  is  possible  to  induce  lesions 
similar  to  those  observed  in  man;  he  concludes,  however,  that  the 
embolic  theory  does  not  explain  all  cases.  Dumeny  believes  that  the 
traumatic  ulcers  result  from  abrasions  in  the  mucosa  or  from  submucous 
hematomata  and  necrosis  of  the  overlying  mucous  membrane.  Gastric 
ulcers  are  frequently  associated  with  anemia,  but  it  is  doubtful  if  the 
blood  condition  produces  the  ulcer;  the  most  intense  anemias  are  often 
unaccompanied  by  gastric  ulceration.  Although  the  hydrochloric  acid 
is  usually  increased,  conclusive  evidence  that  hyperchlorhydria  is  not 
necessary  to  the  production  of  gastric  ulcer  is  clearly  established  by 
the  occurrence  of  jejunal  ulcers  in  operation  cases  in  which  the  acidity 
was  constantly  subnormal.  Duodenal  ulcers  sometimes  follow  cutane- 
ous burns,  and  Devic  and  Chauret  have  recentl)^  called  attention  to  a 
hemorrhagic  duodenitis  accompanying  uremia  and  sometimes  terminat- 
ing in  ulceration.  Attempts  to  establish  a  bacterial  origin  for  gastric 
ulcer  have  been  unsuccessful.  In  Collin's  series  of  262  cases  of  duodenal 
ulcers,  242  were  in  the  first  part.  Peptic  ulcers  are  most  frequent  in 
females  between  twenty  and  thirty  years  of  age,  and  in  males  between 
thirty  and  forty  years. 

Morbid  Anatomy. — It  is  customary  to  divide  the  gastric  ulcers  into 
acute  and  chronic.  Clinically  several  forms  are  recognized,  the  sub- 
division being  based  on  the  symptomatology.  Cases  accompanied  by 
pain  belong  to  the  gastralgic  form;  when  vomiting  is  abundant,  the 
lesion  is  referred  to  as  catarrhal ;  in  the  hemorrhagic  type  hematemesis 
is  a  dominant  symptom ;  when  anemia  and  wasting  are  present  with- 
out gastric  symptoms,  the  process  is  said  to  be  cachectic;  dyspeptic  and 
latent  forms  are  also  recognized.  The  peptic  ulcer  is  usually  solitary,  but 
may  be  multiple,  and  if  many  are  present  they  are  commonly  grouped 
closely  together.  The  ulcer  may  be  situated  in  any  part  of  the  stomach, 
but  is  most  frequent  on  the  posterior  wall  near  the  lesser  curvature  and 
'  "Amer.  Med.,"  Sept.  10,  1904,  p.  452;  bibliography. 


A  L I M  K  \  T  A  \i  Y   C  A  \  A  I, . 


■05 


toward  the  pyloric  en<l  of  the  orijan.  Acconlint,'  to  Pariser  and  Lindner, 
in  200  eases  of  i^astric  ulcer  the  jjosterior  wall  will  be  involved  in  190. 
of  which  4  will  perforate;  and  of  the  10  situated  on  the  anterior  wall, 
8  will  terminate  in  perforation.  The  ulcers  rarely  exceed  2  cm.  or 
3  cm.  in  diameter,  but  a  single  large  lesion  may  possess  a  maximum 
length  of  20  cm.  and  may  encircle  the  stomach.  The  ulcer  may  be 
funnel-shaped,  terraced,  or  saucer-shaped.  In  practically  all  cases  the 
lesion  in  the  mucosa  is  largest;  when  the  muscular  layer  is  involved, 
the  destruction  is  less  than  in  the  mucosa.  In  rare  cases  the  ulcers 
are  undermined  and  the  lesion  in  the  mucosa  small.  In  the  acute 
ulcers  the  margins  are  sharp,  punched-out,  and  on  microscopic  exam- 
ination show  very  little  cellular  infiltration.  In  the  chronic  ulcer  the 
margin  is  elevated  and  formed  bv  a  narrow  zone  of  induration.     Histo- 


'^■'vi:/. 


B  — 


D 


A 
Fig.  346. — Perforatkd  Pkptic  I'tctR  of  Stdmach  (Gastric  L"lcer). 
.4.  Slightly  indurated  marRin.     B.  Exposed  muscular  layer,  iri^inK  rise,  on  this  side,  to  the  appearance  of  a  ter- 
race.    C  Opening  e.xtcndini(  through  the  serosa.     D.  Hyperemic  erosions  of  the  mucosa.     (The  author  is 
indebted  to  Dr.  .\.  O.  J.  Kelly  for  the  specimen  from  which  thi.s  drawing  was  made.) 


logic  examination  of  the  indurated  ring  shows  that  it  is  composed  of 
fibrous  tissue  and  the  usual  cellular  elements  of  a  forming  cicatrix. 
The  floor  of  the  ulcer  may  be  the  muscle  or  serous  layers  of  the  stomach, 
or  some  adjacent  viscus.  Peripheral  adhesion  and  extending  central 
necrosis  may  lead  to  perforation  at  some  distance  from  the  original 
lesion.  Thue  has  recorded  a  case  in  which  the  gastric  ulcer  jjerforated 
the  right  ventricle  of  the  heart.  When  adhesion  to  the  liver  or  spleen 
occurs,  an  extensive  necrosis  may  involve  these  organs.  Robson  men- 
tions 23  possibilities  that  may  occur  in  cases  of  gastric  ulcer:  (i )  Local 
peritonitis  or  perigastritis  with  adhesions;  (2)  Local  suppurative 
perigastritis;  (3)  Subphrenic  abscess;  (4)  Abscess  of  liver,  pancreas, 
or  spleen;  (5)  Fistulous  track  between  the  stomach  and  adjoining  organs, 
46 


yo6  SPECIAL  PATHOLOGY. 

or  the  surface  of  the  body;  (6)  Acute  perforation;  (7)  General  peri- 
tonitis; (8)  Dilatation  of  the  stomach;  (9)  Hematemesis  and  melena; 
(10)  Tumor  of  the  stomach  or  pylorus;  (11)  Cicatricial  stenosis  of  py- 
lorus; (12)  Hour-glass  stomach;'  (13)  Spasm  of  pylorus  causing  inter- 
mittent narrowing;  (14)  Atonic  motor  deficiency;  (15)  Gastralgia;  (16) 
Persistent  vomiting;  (17)  Tetany;  (18)  Acute  or  chronic  pancreatitis; 
(19)  Profound  anemia;  (20)  Pressure  on  or  stricture  of  the  bile-duct, 
causing  j  aundice ;  (21)  Cholecystitis  and  cholelithiasis ;  (22)  Emaciation ; 
(23)  Cancer  secondary  to  ulcer.  The  frequency  with  which  gastric  ulcer 
is  converted  into  gastric  carcinoma  has  been  variously  estimated  at  from 
three  per  cent,  to  fourteen  per  cent.  Mayo  found'  a  history  of  ulcer 
in  sixty  per  cent,  of  his  cases  of  cancer.  In  addition  to  pyloric  stenosis 
it  is  also  possible  for  duodenal  ulcers  to  produce  narrowing  of  the  duode- 
num. In  about  five  per  cent,  of  all  autopsies  cicatrices  resulting  from 
healed  ulcers  can  be  recognized. 

Pyloric  obstruction  may  be  due  to  stenosis  or  to  occlusion  by  foreign 
bodies  lodged  or  impacted  in  the  opening,  or  pedunculated  polypi  may 
be  so  situated  that  they  can  be  forced  against  or  into  the  orifice,  occlud- 
ing it  in  a  valve-like  manner.     Congenital  hyperplastic  stenosis  and  the 
narrowing  incident  to  cicatrization  of  ulcers  and  gummata  have  already 
been  considered.     Cancerous  tissue  may  obstruct  the  pylorus  by  hyper- 
plastic thickening  or  by   contraction.     Adenoid   deposits  in  the   sub- 
mucosa  occasionally  manifest  sufficient  hyperplasia  to  produce  obstruc- 
tion.    Quenu  and  'Petit  have  shown  that  pyloric  stenosis  frequently 
follows  ingestion  of  caustic  liquids;     in  twenty-nine  such  cases,  when 
death  occurred  early,  ten  showed  pyloric  ulceration;   and  of  thirty  cases 
in  which  death  took  place  after  one  month,  in  thirteen  there  was  a 
definite  cicatricial  stenosis.     The  pylorus  may  be  obstructed  by  condi- 
tions acting  from  without.     It  is  said  that  in  gastroptosis,  unassociated 
with  pyloric  prolapse,  traction  on  the  pyloric  segment  of  the  stomach, 
and    consequently    on    the    pylorus,    induces    mechanical    obstruction. 
Cicatricial   tissue,    enlarged   g'lands,    and   other   peripyloric    conditions 
may  cause  collapse  of  the  tube.     Lotheissen^  has  been  able  to  collate 
seventeen  cases  of  duodenal  stenosis  due  to  pancreatic  tumor.     Neo- 
plasms involving  the  bile-duct,  or  contiguous  lymph-nodes,  and  tumors 
of  the  liver,  sometimes  obstruct  the  pylorus.     Axhausem  calls  attention 
to  the  pyloric  stenosis  produced  by  ecchinococcus  cysts  of  the  fiver. 
The  pressure  of  an  enlarged  gall-bladder  or  adhesions  resulting  from 
pericholecystitis  may  obstruct  the  pylorus.     Pyloric  obstruction,  suffi- 
cient to  be  of  clinical  im.portance,  is  always  attended  by  dilatation  of 
the  stomach,  either  acute  or  chronic,  depending  upon  the  rapidity  with 
which  the  pylorus  is  obstructed. 

Dilatation  of  the  stomach  ^  is  defined  by  Riegel  as  a  permanent  en- 
largement of  the  organ  combined  with  motor  insufficiency.  The  condi- 
tion is  also  called  gastric  ectasy  or  gastrectasis.     While  the  recognition 

1  "Wien.  klin.  Woch.,"  1903,  No.  14,  p.  409. 

2  "Deut.  Zeit.  f.  Chir.,"  1905,  Bd.  75,  p.  77. 

3  Nothnao-el's  Encyclopedia  of  Practical  .Medicine,  American  edition,  volume 
on  "Diseases  of  the  Stomach,"  1904,  p.  379-  Craemer,  " Magenerweitermig, 
motorische  Insufficienz  tmd  Atonie  des  Magens,"  Munich,  1903.  Debove  and 
Cardarelli,  "International  Clinics,"  1902,  vol.  iii.  twelfth  series,  p.  356-  ^^^  f^^° 
discussion  on  Dilatation  of  the  Stomach,  "Brit.  Med.  Assoc,"  1903;  '  Brit.  Med. 
Jour.,"  Nov.  I,  1903,  p.  1389- 


AI.IMKNTAKV    CWAI..  707 

of  motor  insunkiency  is  important  in  the  clironic  forms  of  gastric  dila- 
tation, it  is  clear  that  in  some  types  of  the  acute  the  paralysis  of  the 
muscle  is  secondary  to  obstruction.  The  inade(iuatc  motor  power  of 
the  stomach  mav  cause  chronic  dilatation,  or  a  gradually  increasing 
obstruction  at  the  pylorus,  or  in  the  duodenum,  can  exhaust  the  gastric 
muscle  which  previously  was  etVicient.  It  is  possible  to  recognize  acute, 
subacute,  and  chronic  forms  of  gastrcctasis,  and  also  types  which  are 
continuous  and  others  in  which  the  dilatation  is  intermittent. 

Acute  gastric  dilatation,  also  called  acute  gastrectasis,  and  gastro- 
plegia,  or  paralvsis  ot  the  stomach,  in  most  instances  depends  upon 
causes  essentially  identical  with  those  producing  a  similar  affection  of 
the  intestine,  called  i)aralysis  of  the  intestine,  acute  paralytic  distention 
of  the  intestine,  acute  intestinal  dilatation  or  enteroplegia.  As  the 
])athologv  of  these  two  conditions  is  essentially  the  same,  1  shall  con- 
sider them  together,  following  a  number  of  observers  who  have  adopted 
the  term  acute  gastro-intestinal  dilatation/  In  some  cases  the  stomach 
is  primarilv  involved  and  suffers  m(jst ;  in  other  instances  the  dilatation 
begins  in  the  intestine,  to  which  it  may  be  restricted;  mixed  cases 
also  occur.  The  condition  may  result  from  acute  obstruction,  as  by 
foreign  bodies  in  the  pylorus,  volvulus  of  the  stomach  or  intestine, 
strangulated  and  incarcerated  hernias.  There  are  some  cases  that  ap- 
pear to  be  causeless,  and  these  have  been  attributed  to  remote  nervous 
influences,  such  as  neurasthenia  and  hysteria.  The  most  common 
cause,  and  bv  far  the  most  important,  is  infection,  and  it  does  not 
appear  necessary  for  bacteria  to  be  located  in  the  peritoneum,  or  in 
the  cavity  of  the  affected  organs.  In  such  cases  the  paralysis  depends 
upon  the  action  of  toxins  circulating  in  the  blood.  This  factor  is  prob- 
ablv  productive  of  the  gastrointestinal  paralysis  accompanying  pneu- 
monia, scarlet  fever,  and  meningitis.  The  local  influence  of  infection 
is  illustrated  bv  the  intestinal,  and  frequently  gastric  dilatation,  accom- 
panving  peritonitis,  appendicitis,  acute  infections  of  the  pelvis,  chole- 
cvstitis,  and  other  localized  acute  inflammatory  processes  involving  the 
abdominal  organs.  Blows  on  the  abdomen,  and  falls  ^\'ithout  gross 
lesion  of  the  abdominal  viscera,  may  be  followed  by  gastro-intestinal 
dilatation.  It  sometimes  appears  after  anesthesia  and  has  been  attrib- 
uted to  the  anesthetic.  Many  cases  follow  abdominal  operations,  even 
when  evidences  of  infection  are  absent.  Surgeons  refer  to  the  condition 
as  acute  paralytic  ileus  or  adynamic  ileus. 

AUbutt  has  described  a  subacute  dilatation  or  atony  of  the  stomach 
following  infectious  diseases,  particularly  typhoid,  pneumonia,  scarlet 
fever,  and  diphtheria.  In  these  cases  it  is  probable  that  the  bacterial 
toxins  have  altered  the  muscle-flber.  or  the  innervation,  and  that,  with 
the  resumption  of  function,  the  organs  manifest  a  tendency  to  dilate. 

Morbid  Anatomy. — At  autopsy  the  stomach  is  usually  greatly  dilated 
and  the  walls  thin  an<l  flaccid.  The  dilatation  sometimes  ends  at  the 
third  part  of  the  duodenum,  where  the  intestine  is  crossed  by  the  supe- 
rior   mesenteric  vessels  and  nerves;    on  the  other  hand,  it  frequently 

>  Talma.  •Berl.  klin.  Woch."  Feb.  3.  1902.  p.  90.  Herff.  "Zeit.  I.  Gcb.  u. 
Gvn."  (Stuttgart),  xliv.  Lund,  "Jour.  Amcr.  Med.  Assoc."  July  11.  190.^  p.  74- 
Revnier.  "Revue  de  Chir."  Nov.  10.  1003.  p.  59.^.  HofTmann.  •Miinch.  med. 
Woch,"  Nov.  S.   1904.     Kom.  "Deut.  med.  Woch."  xxx.  Nos.   10  and   11.  pp. 

344  and  3S0. 


yoS  SPECIAL   PATHOLOGY. 

extends  into  the  ileum,  which,  with  the  colon,  may  be  enonnously  dis- 
tended. Sometimes  the  walls  are  thin,  almost  transparent;  the  serosa 
may  be  normal,  but  is  usually  drier  than  in  health  and  not  infrequently 
is  the  seat  of  beginning  inflammation.  The  stomach  usually  contains 
more  gas  than  liquid,  and  the  same  is  true  of  the  distended  intestine. 
The  fluid  is  usually  thin,  watery,  or  flocculent;  it  may  be  greenish  or 
brownish  from  admixture  of  blood,  or  from  bacterial  growth.  In  autop- 
sies made  shortly  after  death,  the  mucosa  sometimes  weeps  blood,  or 
bloody  serum.  The  vessels  are  moderately  distended  and  erosions  of 
the  niucosa  are  frequently  present.  When  punctured,  the  aftected 
organs  collapse  without  contracting.  I  have  observed  a  similar  condi- 
tion in  the  bladder,  and  it  is  probable  that  the  flaccidity  of  the  uterus  in 
some  cases  of  puerperal  sepsis  depends  upon  a  similar  anatomic  basis. 

Acute  dilatations  of  the  hollow  viscera,  when  rapid  and  marked, 
are  extremely  fatal ;  the  high  mortality  is  probably  due  to  the  intensity 
of  the  intoxication  rather  than  to  the  dilatation  alone.  Of  the  thirty- 
four  cases  of  acute  dilatation  of  the  stomach  collected  by  Herff ,  twenty- 
nine  of  the  patients  died. 

Chronic  dilatation  of  the  stomach,  or  chronic  gastrectasis,  may 
result  from  pyloric  obstruction  or  atony  of  the  gastric  muscle.  Motor 
insufficiency,  even  when  unattended  by  pyloric  obstruction,  and  gas- 
troptosis,  commonly  gives  rise  to  a  dilated  organ.  All  forms  of  slowly 
evolving  pyloric  obstruction  (p.  706)  increase  the  amount  of  work 
demanded  of  the  propulsive  forces,  lead  to  the  stagnation  of  food,  con- 
sequent fermentation,  chronic  gastric  catarrh,  and  eventually  gastrec- 
tasis. It  is  possible  that  some  of  these  cases  originate  in  the  milder 
form  of  acute  dilatation.  Extreme  ectasy  is  observed  in  pyloric  stenosis. 
Morbid  Anatomy. — Motor  insufficiency  is  not  characterized  by  any 
constant  anatomic  lesions  by  which  it  can  be  identified  postmortem; 
when  dilatation  is  present,  the  organ  may  be  enormously  enlarged, 
particularly  downward  and  toward  the  left.  In  the  beginning  the 
enlargement  is  toward  the  left  rather  than  downward,  but  later,  as  a 
result  of  sagging,  the  stomach  may  extend  to  the  symphysis  and  nearly 
fill  the  left  abdomen.  When  the  obstruction  is  slight  and  the  muscle  cap- 
able of  hypertrophy,  some  thickening  of  the  gastric  wall  occurs;  usually 
this  is  more  marked  toward  the  pyloric  end  of  the  organ  and  is  an  at- 
tempt to  compensate  for  the  increased  resistance.  When  hypertrophy 
does  not  occur,  or  has  been  present  and  has  disappeared,  progressing 
stenosis  causes  wasting,  and  consequently  the  gastric  wall  is  thin. 
Microscopic  examination  in  cases  belonging  to  the  latter  group  discloses 
wasted  muscle  layers  the  cells  of  which  may  be  granular  or  even  fatty. 
In  some  instances  the  muscle  cells  are  hyaline,  suggesting  degeneration 
or  necrosis;  the  elastica  is  usually  fragmented.  The  changes  in  the 
gastric  mucosa  are  determined  by  the  amount  and  character  of  the 
accompanying  gastritis.  Usually  the  mucous  membrane  is  wasted,  and 
the  epithelium  degenerated  and  in  part  desquamated;  the  structural 
alterations  in  the  membrane  are  those  observed  in  whichever  form 
of  gastritis  is  present.  In  marked  cases  the  position  of  the  other  ab- 
dominal viscera  is  altered;  the  colon  sags  and  may  lie  in  the  pelvis, 
and  the  liver  and  spleen  are  pushed  upward  and  toward  their  respective 
sides  by  the  enlarged  stomach.  It  is  alleged  that  in  some  cases  the 
diaphragm  rises,  and  that  even  the  thoracic  viscera  may  occupy  ab- 
normally high  positions. 


AI.IMKNTAKY   CANAL 


•09 


In  both  acute  ami  ihroiiic  jj[astrcctasis  the  secretory  activity  of 
the  stomach  is  perverted.  In  the  acute  (Hhitation  the  gastric  contents 
may  possess  no  digestive  action;  most  of  the  fluid  present  is  evidently 
exudative  in  origin.  It  has  been  demonstrated  that  the  toxicity  of 
the  licjuids  contained  in  the  stomach  and  intestine  in  gastro-intestinal 
paralysis  is  higher  than  normal,  and  probably  many  of  the  symptoms 
are  due  to  absorption  of  the  contained  poisons.  In  the  chronic  dila- 
tation, fermentative  changes,  associated  catarrhal  inflammation,  and 
distention  retard  digestion  and  absorption.  Toxic  substances  are  also 
generated,  but  the  character  of  these  bodies  and  their  ]>hysiologic  action 
are  not  fulh"  known. 

The  gastric  neuroses  include  a  number  of  conditions  for  which  no 
adequate  explanation  is  afforded  by  any  anatomic  change  in  the  stomach. 
Probably  some  cases  of  atony  belong  with  this  group.  In  many  cases 
of  gastralgia  no  structural  lesion  can  be  demonstrated;  in  a  few  instances 
arteriosclerosis  of  the  gastric  vessels  is  present.  Some  manifestations 
of  hysteria,  such  as  riiiiiiuatio)i  and  )itcrycisi)i,  are  included  among  the 
neuroses. 

Tumors  of  the  Stomach.' — Xonmalignant  epithelial  tumors  of  the 
stomach  are  rare.  Mucous  polypi,  or  polyadcno))iata,  are  occasionally 
observed;  of  the  thirty-four  cases  collected  by  the  Fenwicks.  forty-one 
per  cent,  were  solitary,  and  when  multiple,  the  number  present  varied 
from  6  to  200.  It  is  probable  that  some  of  the  so-called  adenomata 
are  types  of  the  polypoid  gastritis  to  which  I  have  already  referred. 
Papillomata  are  rare.  The  most  frequent  tumor  of  the  stomach  is 
carcinoDia,  which  may  be  primary  or  secondary;  the  former  is  the 
more  common.  The  secondary  growths  are  rarely  of  metastatic  origin, 
but  are  usually  due  to  extension  from  some  contiguous  viscus,  such 
as  the  pancreas  or  biliary  passages.  About  eighty  per  cent,  of  the 
gastric  cancers  arise  in  the  narrow  band  of  tissue  extending  from  cardia 
to  pylorus,  and  are  usually  nearer  the  latter  orifice.  The  cardia  is 
involved  in  about  ten  per  cent,  of  the  cases,  and  probably  in  some  of 
of  these  the  neoplasm  arises  in  the  esophagus.  With  regard  to  the 
morbid  anatomy  of  gastric  cancer,  it  is  important  to  recognize  three 
types  of  the  affection:  (r)  The  growth  is  fungoid,  giving  rise  to  a  large 
projecting,  cauliflower,  or  pajnllomatous  mass,  and  manifesting  little 
tendency  to  infiltrate  the  gastric  wall.  In  this  form  ulceration  is  rarelv 
conspicuous.  (2)  Ulcerating  carcinoma  produces  extensive  destruction 
of  the  gastric  wall,  and  often  invades  contiguous  structures.  I  have 
seen  the  ulcer  {)enetrate  the  liver,  in  which  a  large  cavity  formed,  and 
in  another  case  similar  extension  involved  the  spleen  and  opened  the 
splenic  artery,  giving  rise  to  fatal  hemorrhage.  Extensive  necrosis 
affecting  the  spleen,  liver,  or  pancreas  justifies  the  name  gangrenous 
cancer  used  particularly  by  the  French  writers.  The  ulcer  mav  be 
small  and  indurated,  particularly  in  the  scirrhous  form,  and  often  con- 
tracts, giving  rise  to  marked  pyloric  stenosis.  The  margins  of  the 
ulcer  are  sometimes  soft  and  fungoid,  and  in  other  cases  extremely 
hard,  the  density  depending  upon  the  amount  of  fibrous  tissue.     Occa- 

•  Fcnwick  and  Fcnwick.  "Cancer  and  Tum<iurs  of  the  Stomach."  1903. 
Comer  and  Fairhank,  "Practitioner."  June,  1904.  p.  Sio.  Rcnner,  "  Mitth.  a.  d. 
Grenzgebiet.  d.  Med.  u.  Chir."  Bd.  xiii.  H.  2,  p.  113.  Alessandri,  "Mitth.  a.  d. 
Grenzgebiet.  d.  Med.  u.  Chir,"  1903,  Bd.  .\ii.  H.  4. 


yio 


SPECIAL  PATHOLOGY. 


Fig.  347. — Stohl^ch,  Carcinoma   of   Pylorus,  with   Secondary  Nodules  in  the  Retrogastric  Glands; 

External  Surface. 
(Removed  during  life  by  Prof.  E.  E.  Montgomery).  A  sectional  v'iew  of  this  tumor  is  shown  in  Fig.  348.     A. 

Polypoid  growth   projecting  into  stomacli.     B,  B.  Gastric  end  of  pylorus.     C.  Duodenal  end  of   pylorus. 

E    External  surface  of  retrogastric  lymph-nodes;   these  were  remo\cd  from  behind  the  peritoneum. 


Fig.  348. — Stomach,  Carcinoma  of  Pylorus,  with  Secondary  Nodules  in  the  Retrogastric  Glands. 
Section  through  center  of  specimen;   mesial  surface  of  one-half  of  specimen.     Removed  during  life  by  Prof.  E.  E. 
Montgomery.)     External  surface  of  same  mass  is  shown  in  Fig.  347.     A.   Polypoid  growth  projecting  into 
stomach.     B.  Connective-tissue  stalk  of  polypoid  mass.    C,  C.  Gastric  end  of  pylorus.     D.    Duodenal  end 
of  pylorus.     E.  Enlarged  lymph-node.     F.  \ecrotic  area  in  secondary  mass  of  neoplasm. 


AI-IMF.NTAUY    (WNAI,.  711 

sionally  the  ulcerations  arc  iiuiltiplc.  This  anatomic  form  may  encircle 
the  stomach  and  is  one  of  the  causes  of  hour-,i,'lass  contraction.  In  the 
earlier  stay^es  ulcerative  carcinoma  may  be  indistinj^'uishable  from  gastric 
ulcer,  ami  it  is  not  improbable  that  many  of  these  ncojjlasms  are  in- 
stances of  cancerous  transfomiation  of  chronic  gastric  ulcers.  (3)  This 
form  is,  in  my  experience,  extremely  rare;  it  is  characterized  by  a 
diffuse  infiltration  of  the  gastric  wall,  which  becomes  greatly  thickened 
and  often  intensely  indurated  (leather-bottle  stomach).  The  capacity 
of  the  organ  is  greatly  reduced  and  ulceration  is  inconspicuous  or  absent. 
In  rare  cases  the  diffuse  induration  extends  to  the  omentum  and  peri- 
gastric tissues,  but  extensive  necrosis  is  infrequent.  In  some  instances 
of  the  ulcerative  form  diffuse  infiltration  of  the  contiguous  gastric  wall 
produces  localized  thickening  and  induration,  which  rarely  is  extensive. 

C  D 


/;  D 

Fic.  340- — Pyloric  E.vd  or  Stomach;    Marked  Stenosis  of  Pylorus  due  to  Contraction  of  Scirrhois 

CARa.NOMA. 

.1     rv|..rii';      H.  H    Pvloric  wall  greatly  thickened  by  cancerous  infiltration.     C.  Smooth  base  of  cancerous  ulcer. 
D.  D.  Gastric  mucosa  infiltrated  by  the  extending  cancer. 

With  regard  to  the  histologic  type  of  cancer  affecting  the  stomach 
much  confusion  has  arisen,  largely  due  to  the  fact  that  all  hard  tumors 
were  formerly  called  scirrhus,  and  the  soft  and  fungoid  masses  were 
grouped  ^vith  the  encephaloid  cancer.  Of  the  1348  cancers  included 
in  the  Fenwicks'  collection,  863  were  encephaloid.  447  scirrhous,  and 
38  colloid.  Of  1 15  specimens  examined  histologically,  73  were  glandular 
carctnomata,  t^t,  cylindric-cell  epithelioma,  and  q  showed  signs  of  colloid 
degeneration.  Cancer  of  the  stomach  is  infrequent  in  patients  under 
fortv  years  of  age;  less  than  three  per  cent,  of  the  patients  are  under 
thirtv.  The  rapidity  with  which  the  lymph-nodes  are  involved  varies 
in  different  cases.  The  dissemination  by  l)ranches  of  the  portal  vein 
is  common  and  secondary  growths  in  the  liver  may  be  expected. 


SPECIAL  PATHOLOGY, 


Adult  connective-tissue  tumors  of  the  stomach  are  rare.  Myoiiia, 
fibroDia,  and  lipoma  are  occasionally  observed;  sometimes  these  form 
polypoid  growths  and  in  other  cases  the  neoplasm  is  sessile.  Of  the 
175'  cases  of  sarcoma  of  the  alimentary  canal  collected  by  Corner  and 
Fairbank,  58  were  in  the  stomach.  Gastric  sarcoma  may  be  subserous 
and  pedunculated;  about  one-third  involve  the  pyloric  region.  Pyloric 
constriction  and  obstruction  are  less  frequent  than  in  cancer.  Ap- 
proximately thirty-three  per  cent,  of  gastric  sarcomata  undergo  metas- 
tasis to  the  lymph-nodes.  Some  of  these  tumors  contain  an  unusual 
amount  of  smooth  muscle-fibers,  and  are  called  by  some  writers  malig- 
nant mvomata,  or  mvomata  of  the  stomach. 


INTESTINE.! 

The  normal  intestine  is  lined  throughout  by  a  single  layer  of  non- 
ciHated,  tall,  cylindric  epithelial  cells;  the  submucosa  is  abundant  and 
richly  vascular.  Situated  in  the  mucous  membrane  of  the  intestine 
are  many  small,  isolated  areas  of  lymphoid  tissue,  constituting  what 
are  known  as  solitary  glands;  when  these  are  agminated,  the  resulting 
masses  are  known  a's  the  Peyer's  patches.  The  absorbing  surface  is 
enlarged  by  the  presence  of  villi  and  folds;  these  structures  also  in- 
crease the  susceptibility  of  the  intestine  to  injury  and  disease. 

Malpositions  of  the  intestine  are  either  congenital  or  acquired.  The 
former  may  depend  upon  abnormalities  in  the  tube,  mesentery,  or  ab- 
dominal wall.  According  to  Grant,-  most  of  the  reported  congenital 
malpositions,  exclusive  of  hernia,  result  from  abnormal  mesenteric  at- 
tachments He  reports  a  case  in  which  the  mesentery  and  colon  were 
on  the  left  side;  the  ascending  and  descending  portions  of  the  colon 
were  apposed.  The  positions  and  relations  of  the  intestine  are  reversed 
in  situs  inversus  viscerum.^  In  some  cases  the  cecum  is  abnormally 
mobile;  the  appendix  may  be  behind  the  caput  coli.  Of  the  acquired 
malpositions  of  the  intestine,  enteroptosis,  volvulus,  hernia,  and  intus- 
susception should  be  mentioned.  The  causes  of  enteroptosis  are  essen- 
tially the  same  as  those  of  splanchnoptosis,  given  on  page  431.  Pos- 
sibly an  abnormally  long  mesentery  favors  the  condition.  Volvulus 
may  be  acute  or  chronic;  by  some,  the  latter  is  made  to  include  twists 
that  persist,  and  also  recurrent  volvulus.^  In  simple  volvulus  the  gut 
is  twisted  either  on  its  own  axis  or  on  the  axis  of  the  mesentery,  and 
in  compound  volvulus  two  loops  of  the  gut  are  entangled.  Among  the 
causes  of  this  peculiar  form  of  torsion  are  long  mesentery,  physiologic 
and  pathologic  elongation  of  the  bowel,  intestinal  adhesions,  violent 
peristalsis,  such  as  accompanies  indigestion,  chronic  intestinal  obstruc- 
tion, and  violent  exertion  throwing  particular  stress  upon  the  abdom- 
inal muscles.  In  some  cases  the  torsion  involves  the  entire  mesentery. 
Of  121  cases  included  in  Gibson's  paper,  in  36  the  small  intestine  was 

1  The  important  literature  bearing  on  diseases  of  the  intestine  will  be  found  in 
the  following  works:  Nothnagel's  "Encyclopedia  of  Practical  Medicine,"  Ameri- 
can edition,  volume  on  '"  Diseases  of  the  Intestines  and  Peritoneum, "  1904.  Hem- 
meter,  "Diseases  of  the  Intestines,"  vol.  i,  1901;    vol.  ii,  1902. 

^"Amer.    Med.,'   April    26,    1002. 

3  Reichelmann,  "Deut.  Zeit.  f.  Chir.,"  1004,  Bd.  Ixxiv,  p.  345. 

*  Kirchmavr,  "Wien.  Idin.  Woch.,"  Oct.  23,  1902,  p.  1138.  Moynihan,  "Med. 
Chronicle,"  Feb.,   1003.     Vaughan,  "Amer.  Jour.  Med.  Sci.,"  May,   1903. 


ALIMENTAKY    CANAL.  7  I  .^ 

affected;  58  involved  the  sigmoid  tlexure,  and  15  other  parts  of  the 
colon.  Chronic  and  recurring  forms  usually  affect  the  sigmoid  flexure. 
Volvulus  may  occur  in  hernia.  If  unrelieved,  the  twisting  occludes 
the  veins  and.  to  a  lesser  degree,  the  arteries,  colla]iscs  the  gut  at  the 
point  of  pressure,  and  terminates  in  gangrene.  In  ciironic  cases  neither 
the  circulation  nor  tlic  intestinal  lumen  arc  continuously  obstructed, 
although  the  latter  may  be   temporarily  obliterated. 

The  terms  hernia  and  rupture  are  applied  to  conditions  in  which 
a  viscus  or  part  of  a  viscus  protrudes  from  the  cavity  in  which  it  is 
normallv  contained.  As  commonly  employed,  the  term  hernia  means 
a  protrusion  of  the  intestine  or  the  omentum  through  or  into  some 
part  of  the  abdominal  wall.  A  hernia  is  composed  of  a  sac,  the  con- 
tents of  the  sac.  and  its  covering.  Usually  the  sac  is  made  up  of  the 
peritoneum,  which  is  forced  before  the  misplaced  viscus.  As  a  rule, 
at  some  point  in  its  course  the  sac  is  narrowed ;  the  area  of  narrowing 
is  usually  a  constriction  situated  in  the  abdominal  wall,  and  is  called 
the  neck  of  the  sac,  the  body  being  that  portion  external  to  the  con- 
striction. The  covcri}ig  of  the  sac  depends  upon  the  location,  and 
usuallv  consists  of  the  skin  and  the  various  underlying  fasciae.  The 
sac  may  contain  intestine  (enterocele),  omentum  (epiplocele),  or  intes- 
tine and  omentum  (entero-epiplocele).  Occasionally  a  hernia  contains 
the  bladder,  stomach,  large  or  small  intestine  or  parts  of  both,  appendix, 
ovary,  etc. 

Of  the  many  causes  alleged  to  be  operative  in  the  production  of 
hernia,  congenital  weakness  or  defects  in  the  abdominal  wall  are  most 
important.  Such  defects  are  most  common  in  the  inguinal,  femoral, 
and  umbilical  regions.  An  unusually  long  mesentery,  as  in  entero- 
ptosis,  coloptosis,  gastroptosis, — splanchnoptosis, — predisposes  to  hernia. 
Weakening  of  the  abdominal  wall  as  a  result  of  cicatrices,  overdisten- 
tion,  muscular  atrophy,  etc.,  favors  the  occurrence  of  hernia.  Mus- 
cular exertion  that  increases  the  intra-abdominal  tension  is  usually 
termed  an  exciting  cause;  such  effort  is  typified  in  straining  at  stool. 
and  lifting  heavy  burdens. 

Hernias  are  said  to  be  reducible  and  irreducible,  depending  upon  the 
possibility  of  returning  the  displaced  viscus  to  the  abdominal  cavity. 
Reducible  hernias  may  become  incarcerated  as  a  result  of  accumulation  of 
feces  in  the  intestine,  with  or  without  the  presence  of  gas.  Phenomena  of 
incarceration  are.  however,  more  frequent  in  irreducible  hernia.  As  a  re- 
sult of  overdistention  or  contraction  of  the  ring  or  neck  of  the  hernia,  in- 
flammation, or  other  causes  the  circulation  becomes  impeded  or  inter- 
rupted, giving  rise  to  what  is  called  straiii^ulated  hernia.  A  division  of 
hernias  into  internal  and  external  is  sometimes  made.  The  former  include 
those  in  which  the  space  containing  the  displaced  viscus  is  within  the 
trunk  cavity;  for  example,  diaphragmatic  and  retro-abdominal  hernia. 
External  hernias,  as  the  name  indicates,  are  those  in  which  an  external 
tumor  is  recognizable.  The  division  is  arbitrary,  as  many  of  the  so- 
called  external  hernias  may  not  be  sufficiently  marked  to  be  recognized 
except  by  operation  or  postmortem.  With  regard  to  the  site,  hernias 
are  said  to  be  inguinal,  femoral,  umbilical,  ventral,  lumbar,  obturator, 
sciatic,  perineal,  pudendal,  and  diaphragmatic.  About  80  per  cent,  to 
85  per  cent,  of  the  hernias  are  inguinal;  10  per  cent,  to  12  per  cent, 
femoral;  and  about  5  per  cent,  umbilical;  in  642  herniotomies  Gibbon 
found  21  in  which  the  cecum  or  appendix  entered  the  sac. 


714 


SPECIAL  PATHOLOGY. 


Increase  in  the  volume  or  displacement  of  the  solid  viscera  influences 
the  position  of  the  intestines.  The  enlarged  uterus  of  pregnancy  and 
also  pelvic  tumors  displace  the  intestine  upward;  greatly  enlarged 
liver  forces  them  to  the  left  and  downward;  and  when  the  spleen  is 
affected,  the  direction  of  the  displacement  is  reversed.  Alglave^  has 
shown  that  prolapse  of  the  right  kidney  displaces  the  ascending  colon 
and  often  causes  adhesions  which  may  produce  obstruction.  Cysts  and 
solid  growths  in  the  mesentery  and  retroperitoneal  tumors  may  alter  the 
position  of  the  mesentery  and  proportionately  disturb  the  relations  of 
the  intestine. 

Malformations  of  the  Intestine. — Congenital  narrowing,  or  stenosis, 
and  imperforate  areas,  also  called  atresias,^  occur;  sometimes  definite 
parts  of  the  gut  are  absent.  The  most  common  of  these  malformations 
is  situated  near  the  anus,  which,  with  more  or  less  of  the  rectum,  may 
be  absent ;  or  the  anus  may  open  into  a  sac  which  does  not  connect  with 
the  colon  above.  Membranous  septa,  transverse  or  longitudinal,  are 
sometimes  present.  Occasionally  the  anus  is  absent  and  the  rectum 
ends  in  a  blind  pouch,  or  opens  into  the  bladder,  urethra,  or  vagina. 
Stenosis  or  atresia  involving  the  intestines  is  much  less  frequent;  in 
the  duodenum  there  are  48  recorded  ihstances  of  atresia  and  9  of  steno- 
sis. Silberman  has  been  able  to  collect  30  instances  of  atresia  of  the 
jejunum  and  3  of  stenosis.  In  most  instances  the  upper  end  of  the 
ileum  is  afifected;  usually  the  atresia  is  single.  Congenital  narrowing 
or  occlusion  of  the  colon  is  exceedingly  rare.  Atresia  and  stenosis  have 
been  attributed  to  intrauterine  intussusception,  volvulus,  embolism  or 
obliterative  arteritis  affecting  branches  of  the  mesenteric  vessels,  ab- 
normal occlusion  of  Meckel's  diverticulum,  and  fetal  peritonitis.  Clogg 
believes  that  most  instances  of  duodenal  malformation  are  produced 
by  abnormahty  in  the  buds  from  whicli  the  pancreas  and  the  liver  are 
developed.  Atresias  and  stenoses  in  the  lower  part  of  the  ileum  are 
probably  due  to  developmental  errors  in  obliteration  of  Meckel's  diver- 
ticulum. 

Intestinal  diverticula  may  be  congenital  or  acquired.  The  most 
common  of  the  former  is  the  persistence  of  more  or  less  of  the  omphalo- 
mesenteric duct,  and  is  called  Meckel's  diverticulum.^  Mitchell  found 
it  in  2  per  cent,  of  1635  autopsies.  It  may  occur  in  any  part  of  the  ali- 
mentary canal  from  the  esophagus  to  the  colon,  but  is  most  common 
in  an  area  beginning  15  cm.  above  the  ileocecal  valve  and  extending 
upward  150  cm.  When  the  entire  duct  persists,  and  is  patulous,  an 
omphaloenteric  fistula  results.  When  closed  at  the  intestinal  end  and 
open  at  the  umbilicus,  the  condition  is  called  an  omphalic  fistula  or 
sinus.  If  closed  at  both  ends,  a  cyst  is  usually  formed;  if  the  resulting 
cavitv  lies  in  front  of  the  peritoneum,  it  is  called  a  preperitoneal  cyst, 
and  when  attached  to  the  intestine,  an  enterocystoma.  In  some  cases 
a  cord,  resulting  from  persistent  vestiges  of  the  omphalomesenteric 
vessels,   occupies   a   region    corresponding   to   that   in   which   Meckel's 

1  "Rev.  de  Chir.,"  Dec.  10,  1904,  p.  730. 

^  Ktiliga,  "Ziegler's  Beit.,"  1903,  vol.  xxxiii,  p.  4S1.  Krauter.  "Arch.  f. 
klin.  Chir.,"  190^,  Bd.  Ixxiii,  H.  4.  Archambault,  "Albany  Med.  Annals,"  July, 
1904.     Clogg,  "Lancet,"  Dec.   24,   1004,  p.   1770 

*  Moore,  "  Jour.  Amer.  Med.  Assoc,"  Oct.  4,  1902,  p.  810.  Dreyfuss,  "Miinch. 
med.  Woch.,"  Oct.  4,  1904,  p.  1785.  Bunts,  "Annals  of  Surgery,"  Oct.,  1004, 
P-  536. 


ALIMHNTAKV    TAX  A  I.. 


7'5 


diverticulum  is  usually  found.  The  diverticulum  varies  in  size  from  a 
teat-like  projection  to  a  cylindric  body  20  cm.  to  30  cm.  long;  the  aver- 
age length  is  about  7  cm.  The  point  of  origin  is  usually  opposite 
the  mesenteric  border,  but  occasionally  it  is  intramesenteric.  Some- 
times the  free  end  is  bifid,  trifid,  or  lobulated.  Often  the  presence  of 
the  body  is  unattended  by  symptoms;  it  may,  however,  contain  foreign 
bodies,  ulcerate  and  even  perforate,  become  adherent  to  other  parts 
of  the  intestine  or  abdominal  wall,  strangulate,  or  inflame  (diverti- 
culitis). Dobson  has  collected  thirteen  cases  in  which  it  was  inverted 
and  caused  intussusception.  Ekehorn  states  that  it  has  been  found 
in  twenty-two  hernias.  Typhoid  lesions  situated  in  a  diverticulum 
have  been  known  to  perforate,  and  the  ulcerative  and  inflammatory 
lesions  which  affect  it  are  not  unlike  those  involving  the  ajjpendix. 
Other  diverticula  of  congenital  origin  occasionally  occur  in  the  intes- 
tine. Hedinger'  reports  a  case  of  congenital  diverticulum  in  the  ap- 
pendix. False  diverticula-  are  hernias  of  the  mucosa  through  weak- 
ened spots  in  the  muscular  wall.  It  is  generally  held  that  the  true 
diverticula  are  congenital;  the  false,  acquired.  The  walls  of  the  former 
contain  all  the  structures  of  the  intestinal  tube;  the  latter  do  not. 
Usually  the  false  sacs  are  situated  near  the  mesenteric  attachment, 
into  which  they  often  project.  It  is  probable  that  hernia  of  the  mucosa 
occurs  around  or  by  the  side  of  a  vessel  penetrating  the  muscle-layers. 
In  the  case  reported  by  Condit  there  were  two  rows  of  pouches,  each 
diverticulum  about  i  cm.  in  diameter;  Virchow  reported  a  case  in  which 
the  sac  was  the  size  of  a  hen's  egg.  They  frequently  contain  fecal 
matter,  and   sometimes  inflame  and  perforate. 

Dilatation  of  the  intestine  may  result  from"  congenital  or  acquired 
conditions.  The  acute  paralytic  distention  (enteroplegia)  I  have  con- 
sidered with  acute  dilatation  of  the  stomach  (p.  707  ).  Congenital  flap- 
and  valve-like  projections  of  the  mucosa  may  obstnut  the  flow  of  the 
intestinal  contents  and  produce  dilatation  above.  Megacolon,^  con- 
genital hypertrophy  and  dilatation  of  the  colon,  and  "Hirschsprung's 
disease"'  are  names  applied  to  an  enlargement  of  the  large  intestine 
believed  to  be  of  congenital  origin.  In  the  case  reported  by  Formad 
the  colon  contained  22  kilos  (47  pounds)  of  feces.  In  Fiitterer's  pa- 
tient the  large  intestine  measured  66  cm.  in  circumference.  In  4  of 
Duval's  cases  the  condition  was  congenital;  in  t^S  it  began  in  infancy, 
and  in  5  the  symptoms  appeared  later.  No  obstruction  can  be  demon- 
strated; the  wall  of  the  colon  is  thickened,  and  eventually  necrotic  and 
inflammatory  processes  involve  the  mucosa.  The  cause  of  the  condition 
is  undetermined,  although  its  congenital  origin  is  generally  conceded. 
Acquired  dilatations  of  the  intestine  develop  on  the  proximal  side  of 
any  obstruction,  and.  if  formed  slowly,  may  be  attended  by  hyper- 
trophy of  the  muscle-layer.  In  other  cases  there  is  no  increase  in  the 
thickness  of  the  bowel-wall;  on  the  contrary,  a  progressive  thinning 
occurs.     As  chronic  obstructions  usually  occur  in  the  colon,  this  organ 

'  "Vircho\v'.s  Archiv."  IQ04,  Bd.  cl.x.wiii,  p  25.  See  also  Hyde,  "Amcr. 
Jcur.  of  Obstet.,'"    Dec,    1904. 

'Fischer.  "Jour,  of  Rxper.  Med.,"  iqoi,  vol.  v.  \o.  4.  Condit,  "N.V.  Path. 
Soc.,"  April  0.  1002.     Beer   "Amer.  Jour.  Med.  Sci."  July,  1004. 

'  Cheinisse,  "  La  Sem.  Med.."  N*ov.  16,  1904.  "Annals  of  Gyn.  and  Pediatr>-." 
Boston,  Jan.  ig,  1904.  Gourevitch,  "  Prag.  med.  Woch.."  Nov  24  and  Dec.  i. 
IQ04. 


i6 


SPECIAL  PATHOLOGY. 


is  most  frequently  dilated.  Atonic  forms  have  been  described.  Acute 
dilatation  develops  suddenly  and  is  usually  the  result  of  some  rapidly 
acting  cause.  It  is  sometimes  a  sequence  of  chronic  dilatation  and  fecal 
accumulation,  the  latter  suddenly  impacting  the  intestine  at  the  point 
of  narrowing.  Chronic  dilatation  is  insidious,  often  persisting  for 
months,  and  is  commonly  attended  by  obstinate  constipation. 

Intussusception^  or  invagination  is  a  condition  in  which  one  por- 
tion of  the  intestine  is  invaginated  within  an  immediatelv  continuous 
•part.     The  affection  may  be  acute  or  chronic,  and  the  intussusception 
single  or  multiple.     It  is  probably  due  to  irregular  muscular  contrac- 


FiG.  350. — Intussusception  at  Ileocecai.  \al\e.  (Drawing  of  specimen  from  Dr.  Graham's  case  of  intus- 
susceplion;  operated  on  by  Dr.  Heam.)  (Compare  with  Fig.  351.  The  letters  have  the  same  significance 
in  both  figures.) 

A,  A.  Colon.  B.  Point  where  the  ileum  enters  the  intussusception.  The  leader  from  the  letter  B  points  direcdy 
within  the  intestinal  lumen.  A  probe  passed  in  at  B  comes  out  at  C,  which  is  the  ape.x.  The  diagram  illus- 
trates the  course  that  it  must  pursue.  E.  The  point  of  constriction  of  the  ileum,  also  called  the  neck  of  the 
intussusception.  F.  Point  of  slight  eversion  where  the  serous  coat  turns  to  pass  -n-ithin  the  bowel.  G.  Shows 
the  line  of  constriction  in  the  ileum  caused  by  the  ileocecal  valve.  F  to  H,  is  the  external  layer,  called  the 
iiitiissuscipiens;  the  enclosed  part  of  the  intestine,  including  both  inner  layers,  from  B  to  C  is  the  inlussus- 
ceplum.  _  The  specimen  has  been  pulled  through  the  valve  to  show  this  line  of  constriction  and  the  gangrenous 
mass  of  intestine  beyond,  extending  from  G  to  C.  This  point  of  constriction  in  the  chagram  is  indicated  by  a 
slight  depression  at  G.  H.  I.  and  /  show  the  line  of  attachment  of  the  mesentery.  Between  H  and  /.  and 
extending  slightly  beyond  the  line  /,  is  a  fold  produced  by  pulling  the  intestine  through  the  ileocecal  valve 
sufliciendy  to  show  the  gangrenous  process.     (Scale,  one-half  the  natural  size.) 


tion  and  intestinal  spasm,  and  is  not  thought  to  be  of  paralytic  origin, 
although  formerly  this  view  was  generally  held.  Riddell"  reported  three 
cases  occurring  in  a  family  of  four  children,  and  suggests  that  there 
may  be  some  congenital  defect  that  favors  intestinal  invagination. 
Active  purgation,  intestinal  irritation,  diarrhea,  polypoid  tumors,  stenos- 
ing  ulcers,  and  even  jolts  are  believed  to  be  etiologic  factors. 

'Douglas,  'Stirgicai  Diseases  of  the  Abdomen,"  1903.  p.  170.  Hemmeter, 
"Diseases  of  the  Intestine."  1902,  p.  356.  Comer,  "Annals  of  Surgery,"  Nov., 
1903,    p.    690. 

^■'Brit.  ^led.  Jour.,"  Jan.   10,   1903,  p.  72. 


A  I,  I  M  !•:  \ T  A  H  Y   C  ANAL.  7  I  7 

Morbid  A  ihilom  v.-  -At  autopsies  one  ])art  of  the  intestine  is  fre- 
ciucntly  found  invaijinatcd  within  another,  hut  there  is  no  evidence  of 
intlaniniation  or  vascuhir  obstruction,  and  the  ronchtion  is  usually 
heheved  to  have  arisen  durini,'  the  a.Ljonal  period,  or  ])ost!norteni.  Sev- 
eral forms  of  the  disease  are  recoi^nized :  enteric  invagination  occurs  in 
the  small  intestine:  when  the  ileum  is  invai^Mnatci]  tliidti'^h  the  ileocecal 
valve  the  condition  is  called  ileocolic  intussusception  ;  in  ileocecal 
intussusception  both  ileum  and  cecum  are  invai^inated  and  the  valve 
ot"  Rauhin  forms  the  ay)ex  of  the  intussusceptum;  when  the  affection 
is  restricted  to  the  colon,  it  is  called  colic  invagination.  A  section 
throusajh  the  involved   gut   discloses   three  intestinal   layers:    the  outer 


Fic.  351. — Intvssusception  Diagram  Intendkd  to  Show  the  Relation  of  the  Sevehal  Parts  in  Fic..  ^50. 

Till-  oullini's  of  the  caput  coli  and  of  ihi-  apix-ndix  have  been  added  in  order  to  indicate  more  clearly  the  relatiims 

D.  The  apix-ndix.     The  letters  have  the  same  siRnificance  as  in  Fig.  351. 


is  known  as  the  intits.sitscipictis,  or  sheath,  and  the  inner  two  constitute 
the  inttissiistrptitni.  At  the  point  where  the  intussusceptum  enters  the 
intusstscij)iens  there  is  usually  a  constriction  called  the  neck'.  The  part 
of  the  intussusceptum  farthest  from  the  neck  is  known  as  the  apex. 
In  double  intussusception  a  previously  invaginated  portion  is  carried 
onward  en  ina.sse — intussuscipiens  and  intussusceptum — into  the  intes- 
tine below.  Sometimes  the  invaginated  ])ortion  of  the  intestine  is  of 
great  length;  the  ileum  may  pass  through  the  ileocecal  valve  and  pre- 
sent at  the  anus.  As  a  result  of  constriction  at  the  neck  the  circulation 
is  impeded  or  arrested,  and  the  intussusceptum  undergoes  necrosis,  is 
separated,   and   may   be   discharged.      Hermes   records   an   instance   in 


yiS  SPECIAL  PATHOLOGY. 

which  60  cm.  of  the  intestine  came  away  as  a  slough  and  the  patient 
recovered.  In  such  cases  an  adhesion  forms  at  the  neck  of  the  invagi- 
nation and  prevents  escape  of  the  intestinal  contents  into  the  abdominal 
cavity.  The  rapidity  with  which  adhesion  occurs  is  indicated  by  the 
fact  that  at  operation,  within  twenty-four  hours  following  the  intus- 
susception, ninety-four  per  cent,  of  the  invaginations  can  be  disinvagi- 
nated;  by  the  second  day  the  percentage  does  not  exceed  eighty,  and 
by  the  fourth  day  about  one-third  can  be  restored.  The  swelling  in 
the  intussusceptuin  and  the  contraction  of  the  intussuscipiens  nearly 
always  are  sufficient  to  cause  obstruction.  Gibson  found  in  1000  cases 
of  intestinal  obstruction  121  (12  per  cent.)  due  to  intussusception,  and 
Treves  places  the  percentage  higher.  Invagination  is  much  more  fre- 
quent in  children  than  in  adults.  Of  Leichtenstern's  593  cases,  134  of 
the  patients  were  in  their  first  year.  In  about  fifty  per  cent,  of  the 
cases  the  ileum  is  invaginated  into  the  colon.  In  the  14  cases  recorded 
bv  Corner  11  were  double. 

Intestinal  obstruction^  results  from  any  condition  which  impedes  or 
arrests  the  contents  of  the  bowel.  Congenital  stenosis  and  atresias, 
hernia,  volvulus,  and  intussusception  may  obstruct  the  gut.  In  Gib- 
son's study  of  1000  operative  cases  35  per  cent,  were  due  to  hernia,  19 
per  cent,  to  constricting  bands,  19  per  cent,  to  intussusception,  and  12 
per  cent,  to  volvulus.  Stasis  of  the  intestinal  contents  occurs  in  par- 
alvsis  of  the  bowel.  The  condition  may  also  be  produced  by  foreign 
bodies,  fecal  masses,  and  lumbricoid  worms.  A  single  large  bihary 
concretion,  or  congeries  of  gall-stones,  may  obstruct  the  bowel,  par- 
ticularlv  at  the  ileocecal  valve;  according  to  Barnard,  one  case  of  ob- 
struction in  forty-five  is  due  to  gall-stones.  The  intestine  may  be  oc- 
cluded by  external  pressure  due  to  tumors,  cysts,  or  wandering  viscera 
and  also  by  angulation.  (See  Fig.  238,  p.  472.)  Neoplasms  and  cysts, 
stenosing  inflammations,  cicatrized  ulcers,  and  healing  gummata  may 
narrow  the  lumen  of  the  bowel.  Reed  reported  an  instance  of  obstruc- 
tion due  to  chronic  intussusception  produced  by  multiple  polypi.  Ady- 
namic obstruction  results  from  paralysis  of  the  bowel,  which  may  be  due 
to  changes  in  the  muscle-layer,  altered  innervation,  or  to  thrombosis 
or  embolism  of  the  nutrient  vessels.  Distal  to  the  obstruction  the  bowel 
is  approximately  empty,  and  above  the  obstruction  is  distended.  The 
distention  in  chronic  obstruction  may  be  extreme,  and  is  usually  most 
marked  at  or  near  the  occlusion.  At  the  point  of  obstruction  the  mucosa 
and  intestinal  wall  are  often  anemic  and  frequently  necrotic ;  above  the 
occlusion  marked  congestion,  erosions  of  the  mucosa,  and  commonly 
larger  areas  of  necrosis  are  observed.  In  the  intestinal  contents  bacteria 
accumulate  in  large  numbers  and  produce  highly  toxic  substances,  the 
absorption  of  which  gives  rise  to  the  fever  and  accompanying  visceral 
lesions.  Clairmont^  has  shown  that  the  toxic  substances  within  the 
bowel  are  among  the  most  active  of  the  bacterial  poisons.  These  poi- 
sons also  nullify  the  inhibiting  influences  in  the  intestinal  wall,  bacteria 
rapidly  migrate,  and  peritonitis,   often  without   perforation,  promptly 

1  Gibson,  "Annals  of  Surgery,"  vol.  xxxii.  See  al.so  references  to  atresia, 
stenosis,   volvulus,   and   intussusception. 

2  Quoted  by  Carwardine,  "Practitioner,"  Jan..  1905,  p.  87.  See  also  Barker, 
"Lancet,"  Sept.  17,  1Q04,  p.  807,  and  Albeck.'" Arch.  f.  klin.  Chir.,"  Bd.  Ixv,  H. 
3.  P-   569- 


A  L I M  !•;  \  T  A  U  Y   C  A  N  A  L .  7  K , 

ensues.  In  clironic  cases  the  intestine  sometimes  thickens;  this  ma)- 
be  due  to  hypertrophy  and  an  effort  to  overcome  the  obstruction,  but 
is  often  tlic  result  of  ceHuhir  infiltration  (PatcP),  affcctin.i,'  particularlv 
the  subnuicosa  and  musclc-lavcrs. 

The  bacteria  of  the  bowel'-'  are  numerous  in  health  and  enormously 
increased  in  nitlammatory  conditions  affecting  the  mucosa.  Members  of 
the  colon  group  are  always  abundant;  pyogenic  cocci,  streptococci, 
Bacillus  pyocyaneus,  and  several  anaerobic  organisms  are  usually  pres- 
ent. Friedman  found  the  Bacillus  aerogenes  capsulatus  in  nine  of  six- 
teen examinations.  Ordinarily  the  inhibiting  influence  of  the  mucosa 
is  sufficient  to  protect  the  tissues  from  infection,  but  disturbances  in 
the  intestinal  circulation  and  secretion  appear  to  exalt  the  virulence 
of  some  of  the  contained  bacteria  and  to  lessen  the  resistance  of  the 
affected  structures.  It  has  been  demonstrated  that  the  colon  bacillus 
obtained  from  an  inflamed  intestine  is  more  virulent  than  when  culti- 
vated from   Ileal  tin'  ori^'^ans. 

Hyperemia  of  the  intestine  occurs  in  acute  inflammatory  conditions, 
around  areas  of  infarction,  neoplasms,  and  ulcers;  the  blood-supply 
is  also  increased  during  digestion.  Intestinal  hyperemia  also  accom- 
panies peritonitis. 

Congestion  of  the  intestine  results  from  thrombosis  of  the  portal 
vein  or  its  branches,  venal  distomatosis,  diseases  of  the  liver  which 
produce  portal  obstruction,  and  cardiac  and  pulmonary  affections  in 
which  the  venous  tension  rises.  At  autopsy  dependent  knuckles  of 
the  intestine  often  show  hypostatic  congestion  and  may  be  red,  pur- 
plish, or  almost  black,  from  the  large  amount  of  contained  blood;  such 
areas  must  not  be  mistaken  for  antemortem  lesions.  In  congestion 
the  intestinal  mucosa  is  intensely  reddened,  often  purplish,  and  is  fre- 
quently edematous.  Slight  epithelial  desquamation  is  present,  and 
necrotic  changes  in  the  lymphoid  follicles  are  sometimes  observed.  In 
chronic  congestion  and  in  malaria  the  mucosa  is  sometimes  pigmented. 

Mesenteric  thrombosis  and  embolism  are  usually  followed  bv  hemor- 
rhagic infarction-''  of  a  segment  of  the  intestine  the  vascular  supply  of 
which  is  affected.  Endocarditis,  arteriosclerosis,  and  other  causes  of 
embolism  are  usually  present.  Clinically  the  condition  resembles  ob- 
struction, largely  because  the  propulsive  power  of  the  involved  area 
is  quickly  lost.  According  to  Galivardin,  septic  embolism  of  the  mesen- 
teric arteries  may  give  rise  to  aneurysm,  abscess,  or  mesenteric  hem- 
orrhage. With  the  development  of  infarction,  hemorrhage  into  the 
intestine  usually  occurs,  the  mucosa  quickly  undergoes  necrosis,  the 
intestinal  wall  softens,  and  is  rapidly  permeated  by  bacteria;  should 
the  patient  survive  sufficiently  long,  peritonitis  develops. 

Intestinal  hemorrhage  accompanies  inflammations,  ulcerations,  and 
necroses  aflcttiiig  the  mucosa.  The  bleeding  mav  come  from  duodenal 
ulcers  and  from  typhoid,  tuberculous,  and  neoplastic  ulcerations.     Blood 

'"Rev.  de  Chir."    March,   igo2. 

^  Friedman.  "Trans.  Chicago  Path.  Soc,"  IQ02,  vol.  v.  No.  8.  p.  172.  Metch- 
nikolT.  "Bull,  de  I'lnst.  Pasteur,''  1903.  Ford,  "Studies  from  the  Royal  Victoria 
Hospital,"  Montreal,  1903,  vol.  i.  Lanz  and  Tavel,  "Rev.  do  Chir.,  "July  10,  1904, 
p.  4-^.     Hcwetson,    "Brit.  Med.  Jour.."  Nov.  26,  19^4.  p    i4.S7- 

*  Osswald,  "Deut.  Zeit.  f.  klin.  Med,"  vol.  liii.  Audistc^re",  "La  Progres  MM.." 
April  2,  1904.  Jackson.  Porter,  and  Quinbv,  "Jour.  Amer.  Med.  Assoc  ."  June 
4 ,   1094,  p.   1469. 


720  SPECIAL  PATHOLOGY. 

in  varying  quantities  is  constantly  present  in  some  stage  of  dysentery, 
and  in  gangrenous  lesions,  infarction,  intussusception,  and  occasionally 
in  other  forms  of  intestinal  obstruction.  Intense  hyperemias  and  chronic 
congestions  rarely  cause  abundant  bleeding.  The  quantity  of  blood 
may  be  large,  or  the  hemorrhage  may  be  of  the  occult^  type.  Abundant 
hemorrhage  in  the  upper  portion  of  the  intestine  gives  rise  to  tarry 
stools.  When  tLs.  blood  comes  from  the  sigmoid  or  rectum,  it  may  be 
but  slightly  altered  by  the  digestive  action  of  the  intestinal  juices. 

Enteritis  is  an  inflammation  of  the  small  intestine;  when  the  large 
bowel  is  involved,  the  condition  is  called  colitis,  and  when  both  are 
affected,  enterocolitis  or  ileocolitis.  Other  regional  divisions  of  intes- 
tinal inflammation  are  duodenitis,  jcjunitis,  scolecitis  or  appendicitis, 
typhlitis  or  cecitis  (cecum),  and,  when  the  rectum  is  involved,  proctitis. 
Etiologically  and  anatomically  the  inflammations  of  dift'erent  parts  of 
the  intestine  are  characterized  by  essentially  similar  conditions.  One 
part  is  rarely  inflamed  for  any  length  of  time  without  involvement  of 
other  areas;    the  cause  in  each  instance  may  be  the  same. 

Acute  catarrhal  enteritis,  also  called  acute  intestinal  catarrh,  results 
from  various  forms  of  intestinal  irritation;  indiscretions  in  diet,  intem- 
perance, and  food  containing  bacteria  or  certain  types  of  microbic  poisons 
(ptomains,  tyrotoxicon)  are  capable  of  inducing  intestinal  inflamma- 
tion. Climatic  conditions  also  exert  important  influences  in  the  produc- 
tion of  inflammation  of  the  intestine.  The  disease  is  especially  frequent 
in  children,  in  whom  it  is  commonly  produced  by  indigestible  milk  or 
milk  containing  bacterial  products.  Streptococcic  infections  of  the 
udder  of  the  cow  often  infect  the  milk,  which,  in  turn,  induces  an  acute 
catarrhal  enteritis  in  bottle-fed  children.  The  Bacillus  dysenterise. 
Bacillus  enteritidis,  and  highly  virulent  colon  bacilli  are  usually  present 
in  the  intestine;  various  members  of  the  proteus  group  and  strepto- 
cocci are  often  found.  A  catarrhal  enteritis  of  a  mild  grade  may  ac- 
company infectious  diseases,  such. as  typhoid  and  pneumonia,  and  a 
severe  serous  catarrh  results  fro:n  infection  by  the  cholera  spirillum. 

Morbid  Anatomy. — The  mucosa  shows  various  degrees  of  hyperemia, 
which  is  usually  more  marked  in  adults  than  in  infants.  Usually,  in 
protracted  cases,  erosions  occur,  and,  in  prolonged  or  intense  infections, 
definite  ulcers  are  sometimes  formed.  In  other  instances  the  lymphoid 
follicles  are  distinctly  enlarged  (follicular  enteritis).  When  the  resiilt- 
ing  intestinal  discharges  are  rich  in  serum.,  the  condition  is  called  serous 
enteritis.  The  structural  alterations  are  those  of  acute  catarrhal  in- 
flammation (p.  546);  the  mucosa  is  swollen,  varying  numbers  of  leuko- 
cytes are  present  in  the  submucosa,  and  epithelial  desquamation  is  often 
conspicuous.  Microscopic  and  even  macroscopic  hemorrhages  are  occa- 
sionally present. 

Chronic  catarrhal  enteritis,  or  chronic  intestinal  catarrh,  usually 
follows  a  succession  of  acute  attacks,  in  which  case  the  perpetuation 
of  the  inflammation  is  often  due  to  chronic  congestion,  tuberculosis, 
syphilis,  chronic  renal  disease,  and  other  affections  in  which  nutrition 
and  excretion  usually  suffer. 

Morbid  Anatomy. — The  changes  are  essentially  the  same  as  those  ac- 
companying chronic  catarrhal  inflammations  of  the  mucous  mem- 
branes (p.  548).  Follicular  enlargement,  erosions,  and  even  ulcers  are 
'  See  Occult   Hemorrhage,  p.   699. 


AI.IM  I'NTAkY    CANAI..  y2I 

sometimes  present.  vSubmiuous  hyjjcrplasia  and  conse<|uent  atrophic 
clian^es  in  the  overhin'^^  mucosa  arc  trc(|ucntl\-  fouivl  in  j)rotracte(l 
cases. 

Pseudomembranous,  hemorrhagic,  and  gangrenous  forms  of  enteritis 
are  not  common.  Except  in  the  specihc  diseases,  ulceration  is  rarely 
extensive,  and  simple  erosion  is  infreciuent.  The  causes  are  similar 
in  kind  to  those  producin^j  catarrhal  lesions,  and  the  anatomic  chanj^'cs 
follow  the  ^ciicral  outline  indicated  on  p.  557.  Su])i)urative  or  phleg- 
monous enteritis  has  been  described,  but  is  exceedin^dv  rare.  In  pro- 
found sej)sis.  especially  in  ])yemic  conditions,  submucous  abscesses  or 
even  more  extensive  infiltrations  are  sometimes  observed.  In  all  fonns 
of  intestinal  inflammation  some  enlargement  of  the  mesenteric  lymph- 
nodes  usually  occurs;  these  structures  are  pa'-ticularly  affected  in  cer- 
tain infectious  diseases,  and  are  especially  prominent  when  typhoid 
and  tuberculous  ulcerations  involve  the  bowel. 

Appendicitis  may  be  characterized  by  an  inflammation  of  the  mucosa 
or  of  the  mterstitial  tissue,  from  which  extension  to  the  peritoneum  fre- 
quently occurs.  Catarrhal  appendicitis  is  either  acute  or  chronic;  it 
may  result  from  extension  of  inflammatory  processes  from  the  colon.; 
or  arise  independently.  No  doubt  faulty  drainage,  narrowing  of  the 
colonic  orifice  of  the  appendix,  and  the  presence  of  unusuallv  virulent 
organisms  are  important  factors  in  its  production.  Foreign  bodies  and 
appendicular  concretions  are  not  without  influence,  although  their 
importance  has  been  exaggerated.  Some  cases  are  traceable  to  injurv. 
The  colon  bacillus  is  present  in  about  seventy-five  per  cent,  of  the  acute 
cases  and  in  eighty-five  per  cent,  to  ninety  per  cent,  of  the  chronic. 
Pyogenic  cocci,  pneumococci.  Bacillus  pyocyaneus.  typhoid  bacillus, 
and.  less  frequently,  the  colon  bacillus'  occur  without  the  presence  of 
any  other  organism:    usually  a  number  of  bacteria,  are  found. 

Catarrhal  appendicitis  may  be  acute  or  chronic,  and  no  doubt  in 
all  forms  of  appencHcular  inflammation  the  mucosa  is  involved.  The 
swelling  attending  acute  catarrh  narrows  the  orifice  of  the  appendix, 
interferes  with  drainage,  thereby  leading  to  the  accumulation  of  bac- 
teria and  their  products,  and  in  this  way  favors  infection  of  the  sub- 
mucosa.  disturbance  of  the  circulation,  and.  in  marked  cases,  gangrene. 
Chronic  catarrhal  appendicitis  may  follow  the  acute  or  develop  insid- 
iously; the  mucosa  wastes,  the  submucous  connective  tissue  increases, 
and  the  cellular  infiltration  is  often  quite  as  marked  as  in  the  acute 
forms,  although  the  edema  is  usually  less.  In  both  the  acute  and  the 
chronic  form  of  appendicular  inflammation  erosion  and  even  necrosis 
of  the  mucosa  frecjuently  occur,  giving  rise  to  definite  ulcers  (ulcera- 
tive appendicitis).  In  other  cases  pyogenic  bacteria  infiltrate  the  sub- 
mucosa.  polymorphonuclear  leukocyte  accumulation  occurs,  local  areas 
of  necrosis  develop,  and  in  this  way  small  abscesses  are  formed  in  the 
wall  of  the  appendix;  this  is  called  suppurative  appendicitis.  The  ab- 
scesses may  open  into  the  lumen  of  the  tube,  the  i)us  drain  awav,  and 
ulcers  remain.  In  other  cases  the  suppurative  process  extends  toward 
and  perforates  the  serosa  (perforative  appendicitis).  It  is  also  possible 
for  ulcerations  and  other  forms  of  necrosis  to  ojjen  the  appendix,  and 
hence  perforative  j)henomena  may  be  present  in  almost  any  form  of 
severe  appendicular  inflammation.  Bacteria  retained  in  the  cavity  or 
'See  references  to  bacteriology*  of  intestine,  p.  719. 
47 


722  SPECIAL   PATHOLOGY. 

wall  of  the  appendix  may  gradually  propagate  toward  the  surface  (pro- 
pagative  infection)  and  involve  the  serosa,  when  no  lesion  amounting 
to  perforation  can  be  demonstrated.  A  most  important  type  of  appen- 
dicular inflammation  is  that  attended  by  the  formation  of  necrotic 
areas  or  gangrene  of  the  appendix  (gangrenous  appendicitis).  The  con- 
dition is  fulminatingly  acute,  but  may  be  engrafted  upon,  or  constitute 
a  terminal  stage  in  other  forms  of  appendicitis.  It  is  probably  the 
result  of  intense  infection,  or  thrombophlebitis,  or  autochthonous 
embolism  affecting  the  vessels  of  the  organ.  The  area  of  necrosis  may 
be  small,  giving  rise  to  a  circular  or  funnel-shaped  perforation,  or  the 
whole  appendix  may  become  gangrenous.  Any  of  the  foregoing  pro- 
cesses may  admit  bacteria  to  the  peritoneal  cavity  and  induce  a  septic 
peritonitis  which  may  be  local  or  general.  In  some  cases  the  bacteria 
are  in  numbers  insufficient  to  produce  suppuration,  or  it  may  be  that 
the  toxin  alone  diffuses  through  the  appendicular  wall,  and  in  either 
case  a  chronic  productive  periappendicitis  results.  The  serosa  is  thick- 
ened, adhesions  are  formed,  and  eventually  the  organ  becomes  imbedded 
in  a  dense  mass  of  fibrous  tissue  (p.  473).  It  is  probable  that  similar 
results  may  follow  acute  appendicitis,  especially  if  the  attacks  are  re- 
peated. Infections  of  the  appendix  occasionally  induce  thrombosis 
of  the  veins;  such  thrombi,  extending  into  the  branches  of  the  portal 
vein,  produce  emboli  which,  reaching  the  liver,  cause  hepatic  abscess. 
Thrombus  formation  in  the  iliac  artery  or  vein  is  rarely  observed  in 
appendicitis. 

Cysts  of  the  appendix  result  from  occlusion  of  the  orifice  communi- 
cating with  the  colon.  It  is  possible  that  in  some  cases  the  condition 
is  congenital,  and  in  others  inflammatory.  The  cyst  may  be  globular 
or  cylindric;  a  specimen  removed  by  Montgomery  was  nearly  20  cm.  in 
length.  The  fluid  contained  within  such  cysts  is  either  serous  or  mucous, 
and  in  some  cases  is  inspissated. 

Concretions  within  the  appendix  are  usually  due  to  inspissation  of 
the  secretions  and  rarely  contain  foreign  bodies.  The  latter  are  not 
infrequently  found,  occurring  in  about  four  per  cent,  of  the  cases  of 
appendicitis;  usually  they  give  rise  to  no  important  alteration,  and 
even  such  sharp  bodies  as  pins  and  fish-bones  may  be  present-  without 
inducing  marked  structural  alterations  or  inflammation. 

Colitis  (inflammation  of  the  colon)  may  be  associated  with  ileitis 
or  occur  independently  of  inflammation  of  the  small  intestine.  The 
causes  are,  in  many  respects,  similar,  but  the  function  of  the  large 
intestine  renders  it  particularly  susceptible  to  certain  types  of  injury. 
The  feces  within  the  colon  are  firmer,  their  progress  slower,  and  the 
opportunity  for  accumulation  greater  than  in  any  other  part  of  the 
alimentarv  canal.  These  observations  apply  especially  to  the  cecum. 
As  a  result  of  the  peculiarities  just  mentioned  inflammation  of  the 
colon  manifests  a  distinct  tendency  to  chronicity,  particularly  if  the 
cause  be  of  a  kind  that  readily  adapts  itself  to  prolonged  existence 
within  the  mucosa  or  in  the  contents  of  the  organ.  The  inflammations^ 
involving  the  colon  are  catarrhal,  pseudomembranous,  hemorr>-^ic,  and 
gangrenous;  with  the  exception  of  the  last  named  they  may  be  acute 
or  chronic. 

Acute  catarrhal  colitis  is  frequently  associated  with  inflammation 
'  See  Inflammations  of  the  Serous  Membranes,  p.  456. 


ALIMKNTAKY    TAN  A  I.. 


723 


of  the  ileum,  in  which  case  tlie  corKhtion  is  called  ileocolitis,  and,  in 
children,  is  the  anatomic  basis  of  the  clinical  syndrome  known  as  cholera 
infantum.  The  causes  of  acute  colon  catarrh  are  essentially  the  same 
as  those  1  have  already  t,nven  for  acute  catarrhal  enteritis.  The  anatomic 
changes  are  also  similar;  the  colon  affection,  however,  is  prone  to  per- 
sist longer  and  give  rise  to  more  intense  lesions.  Desquamation  of  epi- 
thelium and  superficial  necrosis  are  frequently  present.  In  the  catarrhal 
colitis  associated  with  changes  in  the  follicles  (acute  follicular  colitis) 
these  structures  are  particularly  conspicuous,  and  when  the  process  is 
due  to  violent  or  jirolonged  irritation,  and  especially  when  bacteria 
are  numerous,  the  follicular  necrosis  may  give  rise  to  small  erosions  or 
deeper  ulcers.  The  mucosa  is  usually  intensely  edematous,  red  and 
injected,  soft  and  velvety.  Histologically,  the  interglandular  connec- 
tive tissue  and  the  submucosa  contain  numerous  leukocvtes,  and  the 


-•»■ 


V*'^''<s*y*Oi 


■  r 


Fig.  352. — Hemorrhagic  Coutis. — (Harris.) 
Death  from  Chnmic- Interstitial  Nephritis.     A.  Serosa.     B.  Longitudinal  muscle-layer,     r    Circular  musrlc  layer. 
I>.  Sul)mu(i>sa.     K.   .Ni-ircjsinR  mucos;i.     T.  Slough  on  the  surface  of  the  mucosa;    necrotic  membrane.     C 
.Vrtery  with  c.xfrilialinK  emlothelium.     H.  Vein  with  softened  and  necrosing  wall.     I.  .\re.-»s  of  hemorrhage. 

epithelium  of  the  surface  and  that  lining  the  crypts  is  actively  desqua- 
mating and  often  superficially  necrotic.  Marked  hemorrhage,  partic- 
ularly in  the  dysentery  cases,  is  often  present.  Sometimes  the  pro- 
cess is  distributed  with  remarkable  uniformity;  in  other  cases  it  is 
restricted  to,  or  is  more  intense  in,  definite  areas,  such  as  the  caput  coli, 
splenic  flexure,  and  sigmoid.  Such  localization  is  usually  determined 
by  conditions  leading  to  relatively  prolonged  contact  of  infectious 
matter  with  the  mucosa.  With  the  subsidence  of  the  infection  or 
withd  val  of  other  irritants  the  inflammation  gradually  subsides,  the 
epithelium  regenerates,  the  lymphoid  structures  are  restored,  and  the 
mucosa  may  remain  but  slightly  altered,  although  clinical  observations 
indicate  that  its  susceptibility  to  irritation — particularly  after  a  num- 
ber of  acute  attacks — is  notablv  increased. 


724  SPECIAL   PATHOLOGY. 

Chronic  catarrhal  colitis  usually  follows  the  acute  form,  and  is  due 
to  persistent  action  of  one  or  more  of  the  same  causes.  Constitutional 
vices  which  disturb  metabolism,  particularly  excretion,  often  favor 
perpetuation  of  acute  lesions.  It  is  well  known  that  in  uremia,  inflam- 
mations and  ulcerations  of  the  stomach  and  intestine,  and  especially 
the  colon,  frequently  occur;  subjects  of  renal  disease  are  not  infrequently 
affected  by  chronic  catarrh  of  the  colon.  Chronic  catarrhal  colitis 
is  frequently  a  manifestation  of  dysentery,  the  causes  of  which  I  shall 
presently  discuss.  The  changes  occurring  in  this  form  of  colon  inflam- 
mation are  many  and  varied;  they  are,  however,  of  a  type  usually  ob- 
served in  chronic  catarrhal  inflammations  of  the  mucous  membrane 
(p.  548).  The  surface  of  the  mucosa  is  often  irregular,  sometimes  vel- 
vety, or  even  polypoid.  In  some  cases  marked  thickening  of  the 
mucous  and  submucous  layers  gives  rise  to  undulating  irregular  folds, 
and  in  other  instances  the  formation  of  fibrous  tissue  and  its  subsequent 
contraction  thin  the  glandular  membrane  and  distort  the  tube.  Ulcers 
are  almost  invariably  present;  in  distribution  they  often  correspond 
to  the  areas  of  lymphoid  tissue  (folhcular  ulceration),  which  usually 
are  irregularly  distributed;  the  margins  of  such  ulcers  are  uneven  and, 
when  they  extend,  the  contour  is  sometimes  serpiginous;  an  ulcer 
mav  be  enlarging  in  one  part  and  healing  in  another.  It  is  probable 
that  w^hen  ulceration  is  marked,  the  antecedent  inflammation  was  more 
of  a  gangrenous  or  pseudomembranous  type,  rather  than  catarrhal. 
The  muscular  layer  is  often  thickened,  the  serosa  may  be  fibrous, 
and  the  colon  attached  to  contiguous  structures.  Some  writers  dis- 
tinguish between  chronic  catarrhal  colitis  and  chronic  ulcerative  colitis, 
but  it  is  probable  that  both  are  results  of  persistent  irritation  (infection, 
ameba)  in  tissue  often  weakened  by  previous  local  or  systemic  condi- 
tions. Colitis  polyposa^  is  rare;  Pope's  patient  had  syphilis  and  was 
debilitated  from  other  causes.  Sometimes  in  the  polypoid  masses,  and 
occasionally  in  the  mucosa  when  polypi  are  absent,  definite  cysts  are 
formed,  probably  from  accumulation  within  the  follicles.  This  condi- 
tion has  been  called  cystic  colitis. 

Pseudomembranous  coHtis,  also  called  croupous  coHtis  and  mem- 
branous catarrh  of  the  colon,  occurs  as  an  acute  affection  frequently 
associated  with,  or  constituting  an  important  part  of,  dysentery,  and 
as  a  chronic  or  recurring  lesion,  the  pathology  of  which  is  extremely 
obscure.  The  acute  form  is  characterized  by  the  production  of  a  pseudo- 
membrane  Iving  upon  and  involving  the  superficial  part  of  the  mucosa, 
and  composed  of  cellular  detritus,  leukocytes,  and  mucus,  and  frequently 
containing  fibrin;  the  quantity  of  fibrin  varies  in  different  cases,  and 
in  some  instances  none  can  be  demonstrated  in  the  membrane.  Flakes 
of  membrane  and  sometimes  sheets  and  occasionally  casts  of  the  colon 
may  be  passed  with  the  feces.  At  autopsy  areas  of  attached  mem- 
brane are  frequently  present,  and  irregular  masses  are  usually  loose  in 
the  bowel  cavity.  One  part  of  the  bowel  may  show  the  lesions  of  catar- 
rhal inflammation;  pseudomembrane  may  be  present  in  another  area; 
and  a  third  portion  exhibits  the  changes  usually  observed  in  gangren- 
ous inflammations.  The  infiltration  of  the  submucosa,  and  cellular 
accumulation  between  the  crypts,  are  similar  to  those  described  in  the 
acute  catarrhal  inflammation. 

'Pope,  "Brit.  Med.  Jotir,"  Jvily  23,  1904,  p.  iSo. 


ALIMHNTARV    CANAL.  725 

The  chronic  recurrinj^  uv  relaj)sinj.(  colitis,  also  called  mucous  colitis, 
is  an  affection  about  the  etiology  and  pathology  of  which  we  possess 
little  accurate  information.  Particles  of  membrane,  or  even  large 
casts,  escape  in  the  stools;  the  membrane  is  hyaline,  usually  structure- 
less, and  often  contains  no  demonstrable  fibrin.  The  disease  affects 
adults,  especially  females,  and  is  commonly  associated  with  hysteria, 
nervous  affections,  and  constipation.  It  is  probable  that  in  this  grouj) 
of  cases  a  number  of  conditions  are  included,  some  of  which  are  not 
inflammatory.  Ewald  believes  that,  in  some  instances  at  least,  the 
condition  is  a  neurosis,  and  ])roposes  the  name  myxoneurosis  intestinalis 
membranacea.' 

Gangrenous  colitis,  also  called  diphtheric  colitis  and  necrosing  colitis, 
is  often  associated  with  pseudomeml)ranous  inllammatif)n,  and  ])rob- 
ably  represents  nothing  more  than  a  deeper  necrosis,  due  to  an  infec- 
tion of  greater  intensity.  Large  areas  of  the  mucous  membrane  or 
irregular,  smaller  portions  undergo  a  form  of  coagulation  necrosis  which 
may  extend  into  the  submucosa  or  muscular  layer  and  occasionally 
involves  all  coats  of  the  bowel.  The  necrotic  tissue,  after  separation, 
leaves  irregular  denuded  areas  which,  if  the  patient  survive,  are  con- 
verted into  ulcers.  The  necrotic  fragments  may  be  recognized  in  the 
stools.  Opened  vessels  sometimes  bleed  profusely;  septic  phenomena 
are  often  marked,  and  the  absorbed  toxic  products  may  give  rise  to 
necrotic  areas  in  the  liver  and  spleen,  and  sometimes  induce  an  acute 
nephritis.  Should  the  patient  survive,  chronic  ulcerative  processes 
and  persistent  catarrhal  inflammation  continue  the  structural  altera- 
tions sometimes  for  months  or  even  years.  The  anatomic  changes 
leave  the  mucous  membrane  so  profoundly  altered  that  its  susceptibility 
to  all  forms  of  irritation  is  greatly  increased,  and  consequently  com- 
plete recovery  is  uncommon. 

The  term  dysentery-  is  applied  to  a  number  of  affections  in  all  of 
which,  although  the  ileum  may  also  be  involved,  the  constant  anatomic 
changes  are  situated  in  the  large  bowel.  At  the  present  time  classi- 
fication of  the  dysenteries  is  in  a  somewhat  chaotic  condition;  this  is 
largely  the  result  of  existing  confusion  with  regard  to  the  etiology,  and 
partly  on  account  of  the  difficulty  in  coordinating  clinical,  epidemio- 
logic, etiologic,  and  anatomic  forms  in  such  a  way  as  to  establish  de- 
finite order.  Clinically,  acute  and  chronic  forms  are  recognized;  the 
epidemiologist  is  able  to  detect  sporadic,  endemic,  and  epidemic  forms 
of  the  affection,  and  those  who  study  the  etiology  distinguish — (i)  a 
type  due  to  irritation  by  indigestible  food,  preformed  poisons,  and  irri- 
tants of  various  kinds ;  (2)  another  type. — often  occurring  in  epidemics. — 
clearly  of  an  infectious  nature;  and  (3)  a  series  of  cases  in  which  the 
affection  is  due  to  the  ameba.  The  dysenteries  due  to  spirilla,  and 
those  induced  by  the  Balantidium  coli,^  are  so  infrequent  that  they  may 
be  disregarded.  Of  the  irritative  or  chemic  dysentery,  resulting  from 
the  ingestion  of  preformed  poisons,  we  possess  but  little  accurate  in- 
formation, and  no  observations  justify  giving  it  a  position  distinct  from 
other  forms  of  colitis. 

'  "Amer.   Med.."   Feb     13.   iqo.j.  p.   260. 
'  Broida.  "Arcb.  do  Med.  Exr<cr.."  Nov.,  1003,  p.  S20. 

'  Ehmrooth.  "Zeit.  f.  klin.  Med.."  Bd.  xlix.  p.  ;?i.  Klimento.  "  Ziepler's 
Beit.."   IQ03.   Bd.  xxxiii.  p.   2.S0. 


726 


SPECIAL   PATHOLOGY 


Acute  infectious  dysentery  is  evidently  due  to  some  communicable 
factor,  and,  at  the  present  time,  is  ti^ually  attributed  to  the  Bacillus 
dysenteri£e.'  Anatomically  the  alterations  observed  in  acute  cases  cor- 
respond to  the  different  types  of  acute  colitis  already  described;  the 
changes  in  the  ileum  are  rarely  marked.  In  the  milder  cases  the  lesion 
is  catarrhal,  with  superficial  necrosis  and  some  follicular  swelling;  the 
hyperemia  is  frequently  intense,  and  the  vngse  are  unduly  prominent; 
at  points  ecchymosis  or  distinct  hemorrhage  may  be  present.  Later,  or  in 
more  marked  cases,  pseudomembrane  forms,  or  extensive  tissue  destruc- 
tion manifests  the  necrotic 
tendency  of  the  process. 
The  colon  may  be  grayish, 
or  greenish,  and  contain 
dusky  brown  areas  of  ne- 
crotic tissue.  In  cases  that 
have  persisted  longer  the 
softening  and  thickening 
of  the  colon  are  often  in- 
tense, purulent  collections 
may  be,  found  in  the  sub- 
mucosa,  and  peritonitis  is 
not  infrequently  present. 
It  will  be  observed  that 
the  lesions  do  not  always 
differentiate  the  affection 
from  other  types  of  colitis. 
Amebic  dysentery  ^  in- 
volves the  colon,  particu- 
larly the  caput  coli,  and 
occasionally  the  appendix. 
In  typical  cases  of  the  dis- 
ease ulceration  is  especially 
marked  in  the  lower  and 
anterior  parts  of  the  colon ; 
the  ulcers  are  irregular  in 
outline,  and  the  long  axis 
often  transverse  to  the  axis 
of  the  gut.  Sometimes  the 
floors  of  the  ulcers  are 
honeycombed ;  the  edges 
are  usually  undermined. 
The  changes  apparently 
begin  in  the  submucosa, 
or  at  least — even  before 
are  most  marked  in  that  structure,  which  becomes  intensely 


A 

Fio.  353. — Perforating  Ulcer  of  Colon  (Amebic  Dysentery). 
— {Specimen  presented  to  the  Museum  of  the  Jefferson  Medical 
College  by  Capt.  C.  F.  Kiefjer,  U.  S.  A.) 

A,  A.  .Small  irregular  superficial  ulcers  extending  to  the  submucosa 
only.  B.  Perforation  of  a  terraced  ulcer.  C.  Serosa.  D. 
Muscularis.  The  remainder  of  the  large  irregular  ulcer  ex- 
tends no  deeper  than  the  submucosa. 


tilceration- 


^  See  description  of  the  organism,  p.  141.  at  which  point  the  literature  beai-- 
ing  on  the  bacteriology  and  epidemiology'  of  infectious  dysentery  is  given.  Also 
Craig,  "Med.  Record, "  May  10,  1902 ;  "  Am.er.  Med., "  Oct.  11,  1902,  p.  571,  "Jour, 
of  the  Assoc,  of  Military  Surg,"  June,  1904;  and  "Amer.  Jour.  Med.  Sci.,"  July, 
1904,  p.  145.     Howland,  "Med.  News,"  March  5,  1904. 

^  See  description  of  amebas,  also  literattire  in  foot-note,  p.  181.  Also  Rogers, 
"Brit.  Med.  Jour.."  June  6,  1903,  p.  1315.  Harris,  and  also  Futcher,  "Jour. 
Amer.  Med.  Assoc."  Aug.  22,  1902. 


AI.IM  i:\T.\KY   fANAI..  727 

swollen  and  promptly  intiltrated  l)y  niononuclcar  (.ells.  The  cellular  in- 
filtrate, in  addition  to  small  mononuclear  cells,  contains  larj^er  elements, 
possessing  single  nuclei  and  vesiculated  protoplasm ;  such  cells  resemble 
ameba.  Necrosis  of  the  overlying  mucosa,  and  often  the  adjacent  mus- 
cularis.  follows  the  changes  in  the  submucosa.  The  ameba;  are  most  con- 
s[)icuous  in  the  active  lesion,  and  arc  rarely  found  in  a<lvance  of  the 
cellular  inhltration.  The  walls  of  the  contained  vessels,  especially  the 
veins,  are  inHltratcd  by  the  accumulated  cells,  and  frequently  contain 
thrombi  and  sometimes  ameba\  As  the  process  approaches  the  serosa  a 
hbrinous  inriammation  snnnoimts  the  lesion,  and  adhesion  to  contiguous 


'■    M. 


'■?:l'/i:i.i^rr%'-' 


^^"^ 


Fig.  3S4— Amebic  Dysentery  in  PrrPY  (Third  to  Foirth  Day).— (/f<jrrij.) 
a-e.  Coats  of  intestine,     f.  Necrosis  of  epithelium  at  margin  of  ulcer,    c.  I'Agv  of  ulcer,    h.  Infiltrated  sul>- 

mucos;i. 

structures  commonly  occurs.  Superficial  erosion  or  even  ulceration 
in  which  ameba?  can  not  be  demonstrated  sometimes  accompanies  the 
lesion  and  is  probal)ly  due  to  concurrent  bacterial  infection.  Perfora- 
tion of  the  intestine  is  infrequent.  Of  2.^77  cases  of  tropic  dysentery, 
proltably  amel)ic.  hepatic  abscess  occurred  in  19.3  per  cent. 

Cholera  asiatica'  is  an  infectious  disease   characterized   by   an   in- 
flammation  of   the   intestine   and   evidences   of   systemic   intoxication. 
The  lesion  in  the  intestine  (p.  144)  is  that  of  an  acute  serous  catarrh. 
'  For  description  of  the  organJEm  and  bibliography  see  page  142. 


728 


SPECIAL   PATHOLOGY 


^^■■ 


Typhoid  or  enteric  fever  is  not  properly  a  disease  of  the  intestines, 
although  its  principal  manifestations  commonly  occur  in  these  struc- 
tures. The  organism  associated  with  the  disease  is  described  on  page  238. 
By  the  administration  of  pure  cultures  of  the  typhoid  bacillus  Grunbaum' 
has  produced  typhoid  in  the  chimpanzee.  Dufioco  and  Voisin-  report 
an  illness,  believed  to  have  been  typhoid,  due  to  taking  typhoid  cul- 
ture with  suicidal  intent. 

Morbid  Ajiatoniy. — More  or  less  marked  catarrhal  inflammation  of 
the  ileum  and  colon  accompanies  the  other  intestinal  lesions ;  if  diarrhea 
be  present,  the  acute  intestinal  catarrh  is  usually  more  marked  than 
when  this  symptom  is  absent.  Early  in  the  disease  the  lymphoid  fol- 
licles become  swollen  and  prominent;  hyperemia  is  usually  present, 
but  often  is  not  marked.      Mallory  has  shown  that  the  endothelium  of 

the  lymph-vessels  and  ca- 
pillaries proliferates,  and 
that  fibrin  is  present  in  the 
affected  structures.  In  the 
agminated  follicles — the 
patches  of  Peyer— the  hy- 
peremic  swelling  and  the 
cell  proliferation  are  more 
marked  and  the  bacillar}^ 
infiltration  is  deeper.  The 
patches  are  elevated,  ede- 
matous, and  surrounded 
by  a  slight  zone  of  redness ; 
at  first  the  agminated  node 
is  intensely  engorged  and 
deeply  colored,  but  later 
the  tension  within  the 
|)atch  rises,  the  vessels  are 
occluded  by  hyaline 
thrombi,  less  blood  enters, 
circulation  is  arrested,  ne- 
crosis occurs,  the  slough 
separates,  and  an  ulcer 
results.  The  depth  of  the 
ulcer  is  dependent  upon 
the  extent  of  the  necrosis : 
it  may  involve  only  a  part 
of  the  mucosa,  but  more  commonly  the  entire  thickness  of  the  epithelial 
layer  is  destroyed,  and  the  submucosa  or  muscularis  is  exposed.  The 
edge  of  the  ulcer  is  irregular,  swollen,  and,  it  may  be,  undermined; 
the  base,   after  the  slough  has   completely  disappeared,  is   clean  and 


Fig.  355. — Small  Intestine.  Typhoid  Ulcer  during  the 
Early  Part  of  Third  Week  of  the  Disease.  (Natural 
size.) 

The  long  axis  of  the  ulcer  corresponds  to  that  of  the  bowel;  the 
base  of  the  ulcer  still  contains  the  slough,  or  necrotic  tissue, 
which  is  nearly  ready  to  be  thrown  off;  its  ragged  and  fissured 
surface  is  well  shown. 


^  "Brit.  Med.  Jour.,"  April  9,   1904.  . 

^  "Arch.  Gen.  de  Med.,"  Sept.  i,  IQ03.  See  also  Atlassoff,  "Annales  de  I'lnst. 
Pasteur,"  Nov.  25,  1904,  p.  701  For  literature  on  mori^id  anatomy  of  typhoid 
.see  Mallory, "Jour,  of  Exper.  Med.,"  vol.  iii,  p.  611.  Longcope,  "Bi:ll.  of  the 
Aver  Clinical  Laboratory  of  the  Penna.  Hospital,"  Jan.,  1903,  No.  2.  Baer, 
"Amer.  Jour.  Med.  Sci.,"  May,  1904,  p.  787.  For  complications  of  typhoid  see 
Keen,  "Surgical  Complications  and  Sequels  of  Typhoid  Fever,"  1898.  Also 
Hare,  "The  Medical  Complications,  Accidents,  and  Sequels  of  Typhoid  or  Enteric 
Fever,"    1902. 


ALIMKNTAkV   CAN  A  I..  "J  2() 

smooth.  It  the  slou},'hini,'  i)rocess  be  attended  by  inliltration  and  vas- 
cular stasis  in  the  muscularis,  the  necrosis  may  extend  through  the 
intestinal  wall,  or,  thouj^di  rarely,  perforation  results  from  extending 
lesions  after  the  slough  has  separated.  If  the  lesion  extends  through 
the  wall  of  the  intestine.  i)eritonitis  necessarily  ensues.  Yates  found 
peritoneal  inrtammation,  without  perforation,  73  times  in  4300  cases 
of  tvphoid.  Perforating  ulcers  occur  in  about  four  per  cent,  to  six 
per  cent,  of  all  cases  of  typhoid.  If  a  vessel  of  any  size  be  opened 
during  the  process  of  sloughing,  or  if  a  coagulum  fails  to  form  in  a 
necrotic  vessel,  hemorrhage  results.  With  separation  of  the  slough, 
in  favorable  cases,  repair  begins;  embryonic,  followed  by  granulation 
tissue  develops,  and  epithelial  reproduction  proceeds  from  the  margins 
toward  the  center. 

The  tvphoid  ulcer  is  oval  in  outline,  with  its  long  diameter  in  the 
axis  of  the  bowel;  it  rarely  involves  the  entire  patch,  but  may  do  so; 
the  ulcers  are  most  abundant  and  most  constant  near  the  ileocecal  valve, 
but  may  develop  in  any  ])art  of  the  alimentary  canal  where  the  lym- 
jihoid  elements  are  present.     Chronologically,  infiltration  and   cell-pro- 


h 


_"^v-,^    .        ;i     .*- ■    ■  /-_:..;■'.,-■■.    .....         .    ■;--.     ---.'.-■.•1  ri  O: . 

;--.»-.... -A  ■  \ 

Fio.  3s6.— Section  through  a  Typhoid  Ulcer.  End  of  Second  WttK  ut  inr.  l)i=iLASE.—{SchiHaMs.)     (Partly 

diagrammatic.) 

.1 .  Mucosa  and  submucosa,  the  latter  infiltrated  with  lymphoid  cells.     B.  Muscle-coats  of  intestine.     C.  Serous 

layer  of  intestine,     a.  Adjacent  nearly  normal  mucosa.     6.  Separating  slough. 

liferation  terminate  in  necrosis  about  the  end  of  the  second  week  or  in 
the  beginning  of  the  third  week ;  during  the  latter  the  sloughs  separate ; 
healing  may  not  be  completed  until  clinical  recovery  has  long  been  passed. 
The  typhoid  ulcer  may  occur  elsewhere  than  in  the  alimentary  canal; 
Baer  found  it  present  in  the  larynx  in  about  twenty  per  cent,  of  the 
fatal  cases.  They  sometimes  occur  in  the  ai)pendix  or  in  Meckel's 
diverticulum.  Tlie  ulcer  involves  the  ileum  in  97.5  per  cent,  of  the 
cases.  Rarely  no  ulceration  is  found;  Baer  has  collected  twenty-eight 
cases,  verified  by  bacteriologic  examination,  in  which  intestinal  ulcera- 
tion was  absent. 

With  infiltration  of  the  Peyer's  patch,  and  the  generation  of  poi- 
sons therein,  the  lymphatics  and  blood-vessels  begin  the  absorption  of 
toxins,  whose  influence  may  be  wide-spread;  at  the  same  time  the  bacilli 
gain  access  to  the  viscera,  and  may  be  found  not  only  in  the  patches, 
but  in  the  mesenteric  lymph-nodes,  spleen,  and  liver,  and  frequently 
(ninety  per  cent,  of  the  cases)  in  the  blood.  The  mesenteric  nodes 
are  infiltrated,  and  occasionally  necrotic;  sup])uration  due  to  the  pyo- 
genic activitv  of  the  bacillus,  or  to  mixed  infection  by  pyogenic  cocci, 


73° 


SPECIAL  PATHOLOGY. 


may  occur.  There  are  three  recorded  instances  of  ruptured^  mesen- 
teric node.  The  adjacent  lymi)h-nodes  (retroperitoneal)  may  be  in- 
volved. 

The  spleen  is  enlarged,  soft,  and  may  show  infarction,  rupture,  or  gan- 
grene. (See  Acute  Splenic  Tumor,  p.  4,34.)  The  liver  is  the  seat  of  cloudy 
swelling,  and  quite  constantly  contains  areas  of  coagulation  necrosis. 
The  kidneys  exhibit  a  similar  change,  or,  as  a  result  of  the  intense  tox- 
emia and  bacteremia,  an  acute  nephritis  may  be  present.  The  muscles 
of  the  abdomen  and  the  adductors  of  the  thighs  are  commonlv  altered 


it^. 


'^.^^ 


Fig.  357. — Secti"  i     i        i  -^  i    nn:  l-j>i.i;  of  a  Typhoid  Ulcer,  Beginning  of  Third  Week 

OF  THE  Disease.     (AIulIi  higher  nuigniULaliun  than  Fig.  356.)     (^-inch  objective;   i-inch  projection  ocular.), 

Specimen  hardened  in  corrosive  sublimate,  inliltrated  w-ith  paraffin,  stained  in  hematoxylin  and  eosin,  anci  mounted 
in  balsam,  a.  Mucosa,  which  overhangs  the  margin  of  the  ulcer,  ft.  Submucosa,  infiltrated  with  senim 
and  containing  some  fibrin.  Xear  the  ulcer  well-marked  and  extensive  round-cell  infiltration  is  seen.  c. 
Transverse  muscle-iibers;  immediately  under  the  ulcer  these  will  be  seen  containing  many  round  cells  and 
are  the  seat  of  degenerative  changes  not  discernible  with  this  magnification,  d.  Longitudinal  muscle-fibers. 
e.  Slough  of  necrotic  tissue  matted  together,  and  about  separated,  preliminary  to  being  thrown  off. 

by  hyaline  or  vitreous  degeneration;  rarely,  other  muscles  are  similarly 
affected.  Granular  change  or  cloudy  swelling  may  be  present  in  the 
cardiac  muscle;  an  acute  nonsuppurative  interstitial  myocarditis  (p. 
494)  is  occasionally  observed.  Changes  in  the  bone-marrow,  resembling 
those  occurring  in  the  lymphoid  follicles  of  the  intestine  and  spleen, 
were  present  in  each  of  the  twenty-six  cases  studied  by  Longcope. 
There  was  a  similar  accumulation  of  lymphoid  cells  and  large  endo- 
thelial phagocytes ;  foci  of  necrosis  were  also  frequently  present  in  the 
'  Le  Conte,  "Jour.  Amer.  Med.  Assoc,"  Oct.  22,  1904,  p.  118S. 


Al.lMKNTAKY    CAN  A  I..  7.51 

affecteil  marrow.  It  is  well  known  that  suppurative  processes  and  necro- 
ses not  uncommonly  occur  in  the  bones  after  typhoid,  and  that  the 
bacillus  may  be  obtained  from  such  lesions  long  after  recovery  from 
the  initial  infection.  When  the  complication  occurs  during  or  imme- 
diately after  tvplmid.  it  might  be  accounted  for  by  embolism,  endo- 
thelial changes  in  the  vessels,  or  thrombosis;  such  an  explanation  fails 
to  make  clear  the  long  latent  period  often  present;  it  may  be  that  the 
bacteria  require  some  accessory  factor — such  as  injury— in  orfler  to 
extend  the  inflammatory  process.  The  bacillus  is  frequently  present 
in  the  biliarv  passages,  and  in  some  cases  persists  years  after  the  attack 
of  typhoid.  It  may  give  rise  to  cholecystitis,  which  in  some  instances 
is  suppurative;  gall-stones  often  follow  typhoid  infection  of  the  gall- 
bladder. In  addition  to  the  cardiac  changes  already  mentioned,  en- 
darteritis, endophlebitis,  and  thrombus  formation  are  occasionally  due 
to  infection  bv  the  typhoid  bacillus;  endocarditis  is  less  frecjuent. 
Thayer's'  studies  indicate  that  not  only  may  typhoid  produce  acute 
lesions  in  the  vascular  system,  but  that  it  is  possible  for  it  to  develop 
conditions  which  terminate  in  arteriosclerosis.  A  thrombophlebitis 
sometimes  involves  the  portal  vein  or  its  branches  and.  though  infre- 
quently, other  veins.  Noma  and  other  gangrenous  processes  occasion- 
allv  occur. 

Paratyphoid  fever  is  an  infection  generally  thought  to  be  different 
from  tvphoid,  but  due  to  a  closely  allied  organism— the  paratyphoid 
bacillus- — of  which  Buxton  and,  more  recently,  Fox  recognize  two 
forms.  The  disease  appears  to  be  a  bacteremia  without  constant  ana- 
tomic lesions.  The  intestinal  lesions  are  variable;  the  ulcers  are  des- 
cribed as  resembling  the  necroses  of  dysentery  more  than  those  of 
tvphoid.  Splenic  enlargement  is  present,  but  neither  the  clinical  nor  the 
anatomic  picture  is  sufficient  to  distinguish  the  disease  from  typhoid; 
the  bacilli  isolated  are  intermediate  between  the  colon  bacillus  and 
the  Bacillus  typhosus,  and  the  diagnosis,  clinical  and  anatomic,  must 
be  ba-e  1   on  agglutination  tests. 

Syphilis  of  the  intestine^  occurs  in  both  hereditary  and  acquired 
forms  of  the  infection.  Acute  and  chronic  catarrhal  conditions,  attri- 
buted to  syphilis,  possess  neither  anatomic  nor  clinical  peculiarities 
distinguishing  them  from  similar  manifestations  arising  from  other 
causes.  Svphilitic  ulcerations  may  involve  the  small  and  large  intes- 
tine, but  are  most  frequent  in  the  rectum.  Perforation  occurs,  but  is 
uncommon.  The  ulcers  frequently  result  from  necrotic  processes  af- 
fecting gummata,  and,  when  cicatrized,  usually  give  rise  to  strictures. 
Gumma  without  ulceration  may  also  cause  stenosis.  vSyphilitic  stric- 
tures are  usuallv  in  the  rectum',  and,  acconhng  to  Allingham  and  also 
Matthews,  about  half  of  the  stenoses  occurring  in  the  rectum  are  of 
syphilitic  origin.  Two-thirds  of  the  patients  are  women,  ami  the  con- 
dition is  more  common  in  the  colored  than  in  the  white  race. 

»  "  Johns  Hopkins  Hospital  Bull.,"  Oct.,  1904. 

»  Wells  and  Scott.  "Jour,  oi  Infect.  Diseases,"  Jan.  2  1904,  p.  72.  rienrv, 
"Amer.  Med.."  April  15.  1905.  p.  613.     Fox.   "Univ.  of  Penna.  Med.  Bull..     Apnl. 

■^  Weiss    "Centralbl.  f.  d.  Grenzepebiet.  d.  Med.."  Jena.  1902.  vol.  v.  Nos.   15 
and  16.     Suarez  de  Mendoza.  "Gaz.  des  H6p.  Civils  et  Militaircs."  March  it.  1904^ 
Elder.  "Brit.  Med.  Jour.."  May  7.  1004.  p.  lofiS      Frankcnburper.  "Med.  News, 
Feb.   4.    1905,  p.    204. 


SPECIAL   PATHOLOGY. 


Actinomycosis  of  the  intestine'  is  of  necessity  considered  with  ab- 
dominal actinomycosis  because,  in  many  cases,  it  is  impossible  to  decide 
whether  the  lesion  began  in  the  intestine  or  some  other  abdominal 
viscus.  According  to  Rurnam,  there  are  32  cases  of  actinomycosis  of 
the  a|)])endix  on  record;  the  condition  is  called  perityphlitis  actino- 
mycotica.  Approximately  sixty  per  cent,  of  the  intestinal  infections 
are  in  the  neighborhood  of  the  appendix.  The  lesion  may  be  sup- 
purative or  neoplastic;  the  former  gives  rise  to  abscesses  in  which  the 
fungus  can  readily  be  detected.     In  the  second  variety,  tumors,  which 

are  sometimes  pedunculated,  are  formed; 
neither  necrosis  nor  abscess  formation  is  con- 
spicuous. The  pelvic  manifestations  of  actino- 
mycosis often  appear  to  arise  in  the  organs 
of  reproduction  situated  in  that  area,  but 
may  also  result  from  rectal  infection. 

Tuberculosis  of  the  intestine-  may  be  pri- 
mary or  secondary ;  the  former  is  exceedingly 
rare;  the  latter  is  common  in  all  forms  of 
tuberculosis  in  which  material  containing  bacilli 
is  swallowed.  The  incidence  of  primary  tuber- 
culosis of  the  intestine  is  not  the  same  for  all 
countries,  and  the  affection  is  much  more  fre- 
quent in  children  than  in  adults.  Hunter's 
experience  in  China,  where  tuberculosis  is 
common,  gives  the  lowest  percentage;  he 
found  five  cases  in  5142  autopsies.  Wagener, 
in  Germany,  observed  it  in  16.4  per  cent,  of 
children  under  fifteen  years  of  age;  of  203 
cadavers  of  children,  examined  by  Orth,  in 
only  two  was  there  reason  to  believe  that  the 
intestinal  lesion  was  primary.  It  may  affect 
the  intestine,  giving  rise  to  characteristic  tuber- 
culous ulcers,  or  the  bacillus  passes  through 
the  intact  mucosa  and  is  deposited  in  the 
contiguous  mesenteric  h^mph-nodes.  Secon- 
dary tuberculosis  of  the  intestine  may  be 
miliary,  ulcerative,  or  hyperplastic. 

Miliary  tuberculosis  of  the  intestine  is 
usually  a  part  of  a  general  miliary  tubercu- 
losis. Sometimes  the  tubercles  can  be  recog- 
nized in  the  submucosa,  or,  when  the  peri- 
toneum is  involved,  on  the  serous  surface. 
Chronic  caseous  or  ulcerative  tuberculosis  of 
the  bowel  begins  as  an  infiltration  of,  but  is 
not  restricted  to,  the  adenoid  tissue — usually  a  Peyer's  patch.     After 

'  Zondeck,  "Deut.  Zeit.f.Chir.,"  June,  1903,  Bd.  60,  H.  i.  Letulle,  "  Revue  de 
Gyn  ,"  Paris,  190?,  vol.  7,  No.  4.  Burnam,  "Bull,  of  Johns  Hopkins  Hosp.,"  April, 
1904.      Bell  and  Harris,  "Lancet,"  June  11,  1904,  p.   1656.     See  also  p.   166. 

2  Harris,  "Annals  of  Surgery,"  Nov.,  T902.  Epstein,  "Wien.  klin.  Rund- 
schau," Feb.  28,  1904.  Cullen,  "Amer.  Jour.  Med.  Sci.,"  March,  1904.  Hunter, 
"Brit.  Med.  Jour.,"  May  14,  1904,  p.  1126.  Berard  and  Leriche,  "Revue  de 
Chir.,"  Aug.  10,  1904,  p.  165.  Frohlich,  "Wien.  klin.  Woch.,"  Dec.  15,  1904,  p. 
134.1.     Wagener,   "Berk  klin.   Woch.,"   vol.   xhi,   No.  5. 


Fig.  358. — Small  Intestine;  Sec- 
ondary Tuberculosis;  Mul- 
tiple Tuberculous  Ulcers. 


AI.IMKNTAKY   rANAI..  7.^3 


intiltration  and  the  formation  of  miliary  tuberi-les,  caseation,  follo\ve<l 
by  necrosis  of  the  overlying  epithelium,  gives  rise  to  an  ulcer. 
(See  p.  152.)  The  long  axis  of  a  tuberculous  ulcer  is  usually,  although 
not  invariably,  transverse  to  the  axis  of  the  intestine;  this  ])ecu- 
liaritv  is  due  to  the  distribution  of  the  lymphatics  and  vessels  along 
the  course  of  which  the  ulceration  extends.  Commonly  the  infection 
is  propagated  through  the  intestinal  wall,  and  miliary  tubercles 
appear  immediately  beneath  the  subserosa.  The  edge  of  the  ulcer 
is  usuallv  irregular,  the  margins  undermined,  and  the  floor  necrotic 
and  often  containing  macroscopic  tubercles  in  which,  by  direct  or  by 
transmitted  light,  caseous  centers  can  usually  be  recognized  (p.  149)- 
A  catarrhal  inflammation  of  the  contiguous  mucosa  is  commonly  j)res- 
ent.  As  a  result  of  fibroid  changes  in  the  floor  of  the  ulcer,  and  espe- 
cially in  the  serosa,  contraction  frequently  occurs,  giving  rise  to  steno- 
sis. Perforation  is  infrequent.  The  mesenteric  nodes  are  commonly 
involved  and.  in  some  cases,  the  retroperitoneal  lymphatic  tissues  are 
also  affected.  Extension  to  the  peritoneum  may  give  rise  to  tuber- 
culous peritonitis.     (See  p.  475-) 


/  / 

Fig.  3SQ. — TuBERClLOUS  Ulcer.— (5f/im<iuj.)     X    i^  diameters. 
a    Mucosa,     h.  Submucosa.  in  which  are  numerous  tubercles.  /  and  /';   in  the  latter,  caseation  is  advanced,     r. 
Mu.scularis.     d.  Serous  covering,  in  which,  at  /,  /,  are  two  tubercles,     g.  Opening  of  ulcer  into  the  lumen  ol 
the  canal. 

Chronic  hyperplastic  tuberculosis  of  the  intestine  usually  occurs  in 
the  neighl)orhood  of,  or  is  primary  in,  the  cecum.  The  intestinal  wall 
of  the  affected  area  may  be  enorniously  thickened,  sometimes  measur- 
ing I  cm.  from  serosa  to  mucosa.  The  thickening  is  often  the  result 
of  fibrous  tissue  hvperplasia  in  which  characteristic  tubercles  are  scanty 
and  occasionallv  absent  (p.  153).  The  overlying  serosa  is  greatly  thick- 
ened, and  often  is  (irmly  attached  to  contiguous  structures.  The  thick- 
ened nodule  is  sometimes  sausage-shaped  and  occasionally  can  be  felt 
through  the  abdominal  wall.  By  parietal  adhesion  and  extension  the 
lesion  is  propagated  through  the  belly-wall  and  at  points  opens  exter- 
nally, giving  rise  to  fistulous  tracks  which  communicate  with  the  primary 
focus  of  the  infection.  Although  the  lumen  may  be  narrowed  sufti- 
ciently  to  cause  obstruction,  ulceration  of  the  mucosa  is  not  invariably 
present.  Usuallv  the  histologic  picture  of  tuberculosis  can  be  identified, 
but  sometimes  characteristic  tubercles  and  bacilli  are  difficult  to  dem- 
onstrate. The  nearest  lymph-nodes  are  almost  invariably  affected, 
although  rarelv  is  the  involvement  as  extensive  as  in  the  caseous  and 


734 


SPECIAL  PATHOLOGY. 


ulcerative  form  of  intestinal  tuberculosis.  The  condition  is  frequently 
mistaken  for  a  malignant  growth,  and  is  amenable  to  operative  treat- 
ment, after  which  an  occasional  patient  recovers.  The  extensive  fibrous 
changes  are  evidences  of  considerable  resistance  on  the  part  of  the 
patient,  or  infection  by  bacilli  possessing  slight  virulence. 

Tumors  of  the  Intestine. — Papilloma  is  occasionally  seen  around  the 
anal  border,  but  is  not  common.  Adenoma}  may  occur  in  any  part  of 
the  canal,  and  is  especially  frequent  in  the  rectum.  It  is  usually  soli- 
tary; occasionally  two  or  three  are  present,  and  in  rare  cases  large 
tracts  of  the  mucous  membrane  are  covered  with  these  tumors.  In 
the  beginning  adenoma  is  sessile,  the  surface  rapidly  becomes  tuberous 
and  papillomatous  (papillary  adenoma),  and  in  many  cases  a  pedicle 
forms.  It  is  probable  that  the  growth  is  induced  by  local  irritation; 
it  is  not  infrequently  observed  in  venal  distomatosis,  in  which  condition 
the  ova  of  the  parasite  are  usually  found  in  the  tumors.     In  infancy 


^  jjljli.  v>"' 


Fig.  360. — Hyperplastic  Tuberculosis  of  Small  Intestine.     Note  the  fibrous  hyperplasia  in  the  submucosa' 

A-F.  Layers  of  the  intestinal  wall.     g.  Irregular  tubules  enlarged  and  proliferating,     h.  Small  crypts,  branched. 

I.  Cystic  dilatation  of  crypts,     j,  j.  Tubercles  in  subserosa.     k.  Tubercles  in  circular  muscular  coat. 

and  childhood  adenomata  are  benign,  but  in  middle  life  they  are  fre- 
quently converted  into  carcinoma  (p.  319).  Carcinoma  of  the  intestine 
is  the  most  frequent  tumor  of  the  bowel ;  it  may  be  situated  anywhere 
between  the  duodenum  and  anal  border,  but  is  commonest  in  the  rec- 
tum. Leichtenstern,  in  4567  cancers,  found  143  arising  in  the  rectum 
and  35  in  other  parts  of  the  intestine.  Brill,^  in  770  cases  of  intestinal 
carcinoma,  found  t,^  in  the  small  intestine.  Petersen  and  Colmers,^ 
in  a  study  of  carcinomata  of  the  digestive  tract,  found  66  in  the  stom- 
ach, 22  in  the  colon,  and  212  in  the  rectum.  According  to  these  ob- 
servers cancer  remains  locaHzed  longer  when  the  rectum  is  involved 
than  when  the  stomach  is  affected.     Of  41  duodenal  cancers  collected 

1  Ball,  Erasmus  Wilson  Lectures,  "Brit.  Med.  Joiir.,"  Feb.  21,  1903,  p.  413- 
^  "Amer.  Jour.  Med.  Sci.,"  Nov.,   1904,  p.  824. 
^"Beit.   z.   klin.   Chir.,"    1904,   Bd.   xliii. 


A  1. 1  M  !•;  N  T  A  H  \    C  A  N  A  L .  735 

by  Rolleston  the  averai^e  a^'e  of  the  jjatients  was  fifty-two  years.  When 
situated  in  the  first  i)art  of  the  iluotlenum,  it  is  called  jnxla pyloric  duo- 
denal caniiionui;  siipra-aiiipitllary  cancer  arises  just  above  the  openinj^ 
of  the  bile-duct;  pcri-anipullary  carcinoma  surrounds  the  orifice  of  the 
bile-duct;  infra-aniptillary  or  jiixki jejunal  cancer  occurs  in  the  lower 
part  of  the  duodenum.  Of  the  25  carcinomata  of  the  colon  collected 
bv  Clo*ji^,  S  were  in  the  cecal  region,  3  in  the  hejjatic,  6  in  the  splenic, 
and  8  in  the  rectosigmoid  areas.  There  are  about  twenty  recorded 
cases  of  primary  carcinoma  of  the  appendix.*  Two  distinct  types  of 
cancer  of  the  large  bowel  may  be  recognized:  one  in  which  the  tumor 
involves  several  centimeters  of  the  bowel  and  is  soft,  with  little  tendency 
to  obstruct.  The  second  form  involves  a  smaller  area,  is  often  circum- 
ferential and  usually  contracts,  giving  rise  to  a  stricture.  Of  all  the 
cancers  of  the  bowel,  the  last-named  group  remains  localized  longest. 
The  softer  tumors  are  usually  cylindric-cell  carcinomata;  the  denser 
masses  are  commonly  scirrhous  cancers.  In  the  absence  of  obstruc- 
tion cancer  of  the  bowel  may  be  latent  and  give  rise  to  no  symptoms 
prior  to  those  due  to  metastasis.  The  great  vascularity  of  the  intestine 
favors  infiltration  of  the  veins,  involvement  of  the  portal  branches,  and, 
consecjuently,   secondary  growths  in   the  liver  are  frequent. 

Connective-tissue  tumors  of  the  intestine  are  uncommon.  Gross - 
has  been  able  to  collect  22  instances  of  intestinal  lipoma.  Ward  has  in- 
creased the  number  to  37,  but  included  those  from  all  areas  of  the  ali- 
mentary canal.  They  frequently  become  polypoid,  and  are  sometimes 
detached  and  passed  with  the  feces;  Ray  reported  a  case  of  intus- 
susception due  to  a  polypoid  lipoma.  Fibromata,  osteomata,  and  myo- 
mata  are  infrequent  tumors  of  the  intestine:  in  location  they  may  be 
submucous,  ])olypoid,  or  subserous.  Sarcoma  of  the  intestine  is  rare: 
of  106  malignant  tumors  involving  the  bowel.  Mikulicz^  found  3  sar- 
comata of  the  small  intestine  and  2  of  the  colon;  the  series  also  includes 
5  carcinomata  of  the  small. and  95  of  the  large  bowel.  Of  the  175  sar- 
comata of  the  alimentary  canal  collected  by  Comer  and  Fai,  ^ank,^ 
65  were  in  the  small  intestine,  20  in  the  ileocecal  region,  11  in  th  large 
intestine,  and  7  in  the  rectum.  The  growi;h  may  be  annular,  piaque- 
like,  or  f)olypoid,  or  two  of  these  conditions  may  be  combined.  In 
one-third  of  the  cases  lymphatic  metastasis  occurred,  and  in  9  instances 
there  were  secondary  growths  in  other  organs.  The  round-cell  sarcoma 
is  the  most  frequent,  although  all  types  have  been  observed;  Treves 
reported  a  case  of  melanotic  sarcoma  of  the  intestine.  Of  the  45  in- 
testinal sarcomata  collected  by  Lecene.'^  only  2  narrowetl  the  lumen 
of  the  intestine. 

I  have  already  (p.  480)  referred  to  retroperitoneal  neoplasms  and 
cysts. 

The  intestinal  lesions  accompanying  venal  distomatosis  are  described 
on  page  194. 

Enterolithiasis  consists  in  the  formation  of  definite  enteroliths,  or 

'  Eltinp,  "Annals  of  Surper>',"  April,  1003,  p.  540. 

'  '•  Wien.  klin.  Woch.,"  Nov.  15,  1900.  See  also  Ward,  "Albany  Med.  Annals," 
Jan..   1004. 

*  "Arch.  f.  klin.  Chir.,"  1903,  Bd.  ixix,  No.  i. 
*"  Practitioner, "   June,    iqo4,   p.    810. 

*  Th^se  de   Paris,    1004,  Steinheil. 


736  SPECIAL  PATHOLOGY. 

the  presence,  in  the  intestine,  of  finely  granular  earthy  matter  called 
intestinal  sand.  Enteroliths  arise  in  sacs  or  pockets,  such  as  diverti- 
cula, and  in  the  appendix;  they  are  composed  of  an  organic  basis,  con- 
sisting of  inspissated  fecal  matter  and  desquamating  cells,  into  which 
calcareous  salts  are  infiltrated,  it  is  possible  that  some  of  the  entero- 
liths are  derived  from  the  biliary  passages  or  the  pancreas,  although 
it  is  manifestly  improper  to  consider  gall-stones  and  pancreatic  calculi 
with  the  intestinal  concretions.  Analysis  of  intestinal  sand,  in  the  case 
reported  by  Bedford,^  showed  that  it  contained  5  per  cent,  of  moisture, 
28  per  cent,  of  calcium  phosphate,  5  per  cent,  of  calcium  carbonate, 
less  than  i  per  cent,  of  magnesium  phosphate,  and  60  per  cent,  of  or- 
ganic matter;  I  have  omitted  the  fractions.  McNamara  suggests  that 
intestinal  sand  may  be  due  to  a  reversionary  action  of  the  epithelium 
of  the  rectum  or  colon  to  the  egg-shell  forming  function  of  birds. 

Hemorrhoids,  or  piles,  are  vascular  masses  occurring  in  the  lower 
rectum  and  around  the  anal  border;  they  are  usually  produced  by 
varicose  dilatation  of  the  hemorrhoidal  veins.  Reinbach's  conten- 
tion that  new  vessels  are  formed  is  probably  correct.  The  older  view 
that  hemorrhoids  were  due  to  cirrhosis  of  the  liver  and  heart  disease 
is  no  longer  insisted  upon.  Von  Recklinghausen  called  attention  to 
the  fact  that,  under  practically  all  normal  conditions,  no  matter  what 
posture  the  body  is  in,  the  tension  in  the  hemorrhoidal  veins  is  elevated, 
and  must  be  influenced  by  gravity;  the  absence  of  valves  intensifies 
such  action.  When  outside  the  sphincter,  they  are  called  external 
piles,  and  when  within,  internal  piles;  cutaneous  piles  are  external 
hemorrhoids  just  beneath  the  skin.  Injury  and  infection  frequently 
give  rise  to  a  thrombophlebitis  terminating  in  the  formation  of  clots 
which  sometimes  proceed  to  suppuration  and  may  even  produce  pyemia; 
in  other  instances  organization  of  the  thrombus  occurs.  Such  cicatrized 
areas  may  constitute  tags,  or  flaps,  or  even  polypoid  masses.  The  ven- 
ous stasis,  and  consequent  capillary  congestion,  are  frequently  attended 
by  hemorrhage  (bleeding  piles). 

'  "Brit.  Med.  Jour.,"  Dec.  6,  1902,  p.  1764.     See  also  Duckworth  and  Garrod, 
" Medico-Chirttrg.  Trans.,"   1901,  and  "Lancet,"  March  8,   1901. 


CIIAI'TI-R   XI. 
LIVER.' 

Normal  Structure  and  Function.  In  a  nunil)er  of  wavs  the  liver 
rcscmhles  the  niuccjus  membranes  in  that  the  connective  tissue  pass- 
in,i^  throut^hout  the  or^an  corresponds  to  the  basement  membrane, 
and  the  cell  elements  of  the  lobules  to  the  epithelium:  uj)on  the  latter 
the  functional  activity  of  the  organ  depends.  The  lobules  are  formed 
of  hepatic  cells  arranged  in  rows  radiating  from  a  common  center. 
The  blood-supply,  derived  from  the  portal  vein,  passes  from  the  per- 
iphery of  the  lobule  toward  the  center;  the  course  taken  by  the  blood 
from  the  hepatic  artery  is  of  necessity  similar,  as  the  blood  derived  from 
the  two  sources  finds  its  e.xit  by  the  one  route — the  hepatic  vein,  which 
leaves  the  center  of  the  lobule.  Schaffer  has  approved  the  view,  ad- 
vanced by  Prowicz,  that  not  only  do  the  biliary  capillaries  arise  within 
the  cell,  but  that  there  are  intracellular  nutritive  canaliculi ;  whether 
these  latter  structures  communicate  with  the  blood-vessels  or  the  lymph- 
atics of  the  organ  is  still  a  matter  of  doubt,  but.  in  either  case,  vascular 
stasis  might  directly  influence  the  nutrition  of  the  cell  and  in  this  way 
offer  an  explanation  for  the  marked  changes  occurring  in  the  hepatic 
cell  as  a  result  of  impeded  circulation.  The  existence  of  intracellular 
nutritional  canals  would  also  afford  a  histologic  explanation  for  the 
cell-necrosis  observed  in  various  intoxications,  as,  by  such  a  route,  poi- 
sons would  be  brought  into  intimate  contact  with  the  cell  protoplasm. 
The  biliary  capillaries  arise  within  the  lobule  and  are  probablv  con- 
nected with,  and  penetrate  the  hepatic  cell  through  the  intermedia- 
tion of  minute  channels,  called  intracellular  biliary  canaliculi.  The 
existence  of  such  spaces  enables  us  to  understand  why  retention  of  bile, 
as  the  result  of  obstructive  disease  of  the  hepatic  ducts,  exerts  such  a 
deleterious  influence  on  the  liver  cells. 

The  lobule  is  the  gland  unit  and  the  hepatic  cell  is  the  cell  unit. 
The  gland  differs  from  all  other  glands  in  its  blood-supplv:  there  is  the 
usual  arterial  afHux.  rej)resented  by  the  hepatic  arterv;  to  this  is  added 
the  portal  supply — an  enormous  volume  of  blood — brought  from  the 
digestive  canal,  laden  with  the  products  of  food  metabolism.  The 
portal  vein  is  distributed  to  the  periphery  of  the  lobule,  and  the  zone 
immediately  adjacent  is  known  as  the  portal  vein  zone;  in  the  center 
of  the  lobule  is  the  hepatic  vein,  draining  the  blood  from  the  lobule, 
and  the  tissue  immediately  surrounding  this  is  known  as  the  hepatic 
vein  zone:  between  the  two  areas  just  indicated  lies  a  zone  called  the 
intermediate  or  hepatic  artery  zone.  Histologically  and  phvsiologicallv, 
these  zones  are  not  differentiated,  but  disease  processes,  as  will  be  seen 
later,  outline  them  in  a  more  or  less  well-marked  manner. 

'  For  information  or  literature  eonccmintr  diseases  of  the  liver  consult  "Xoth- 
nagel's  EncyclopeHia  of  Practical  .Medicine,"  .American  edition,  volume  on  "Dis- 
eases of  the  Liver.  Pancreas,  and  Suprarenal  Glands."  iqo,^  Also  Rolleston, 
"Diseases  of  the   Liver.  fiall-Bladder,  and   Bile-Ducts."    1905. 

4R  737 


738  SPECIAL  PATHOLOGY. 

The  lobule  is  surrounded  by  connective  tissue,  which  is  continuous 
with  that  of  the  median  fissure  and  the  capsule,  and  is  known  as  the 
capsule  of  Glisson;  in  this  the  portal  vein,  the  hepatic  artery,  and  the 
bile-ducts  ramify,  and  these  carry  into  the  lobule  enough  of  the  connec- 
tive tissue  for  support.  In  man  the  lobule  is  not  sharply  differentiated, 
and  a  number  of  lobules  often  appear  confluent.  By  confluence  or 
juxtaposition  many  lobules  form  a  lobe,  and  these  lobes  constitute  the 
organ.  The  portal  vein,  representing  the  collected  blood  from  the  ali- 
mentary canal  and  spleen,  is  of  itself  a  circulation,  in  the  sense  that 
there  is  a  capillary  system  at  either  end.  It  differs  from  the  other 
blood  systems,  pulmonary  and  S3'stemic,  in  that,  between  the  two 
capillary  areas — the  one  in  the  intestine,  stomach,  etc.,  and  the  other 
in  the  liver — there  is  no  propelling  body,  and  the  blood  must  flow,  in 
this  subsidiary  circulation,  by  reason  of  the  cardiac  force  distributed  to 
the  capillary  system  in  which  the  portal  vein  finds  its  origin.  Patho- 
logically, this  is  of  the  greatest  importance,  for  when  the  general  circu- 
lation is  feeble,  whenever  there  is  a  tendency  to  stagnation,  to  venous 
stasis,  how  unfortunately  situated  is  the  portal  system  to  escape  the 
inevitable  result!  When  the  blood  leaves  the  surface,  as  in  the  chill 
of  malaria,  and  there  is  a  tendency  to  distention  of  the  veins,  those  of 
the  portal  circulation  are  most  prone  to  suffer.  So  it  is  that  diseases  of 
the  lung  or  heart,  which  impede  the  onward  flow  of  the  blood,  partic- 
ularly in  the  veins,  evince  their  most  marked  secondary  alterations  in 
the  hepatic  and  intra-abdominal  digestive  structures. 

Physiologists  have  agreed  that  the  liver  performs  the  following 
functions : 

1 .  Hemolytic :  Disorganization  of  blood  elements  is  necessary  to  the 
production  of  bile  coloring-matter,  and  it  is  generally  believed  that 
this  hemolysis  is,  at  least  in  part,  a  function  of  the  liver,  or  is  begun 
in  some  other  organ,  as  the  spleen,  and  completed  in  the  hepatic  tissues. 

2.  Secretory:  Bile  is  not  only  eliminated  by  the  liver,  but  is  manu- 
factured by  the  hepatic  cells;  the  importance  of  this  has  been  consid- 
ered when  discussing  the  pathology  of  jaundice  (p.  234). 

J.  Urea  production:  The  liver  is  believed  to  be  an  essential  factor 
in  the  production  of  urea. 

4.  Glycogenic :    Glycogen  is  manufactured  in  the  liver. 

5.  Antitoxic:  The  interception  of  poisons.  This  function  has  been 
demonstrated  with  regard  to  the  hepatic  action  on  strychnin,  of  which 
the  dose  by  the  stomach  or  injected  into  the  hepatic  blood-supply  may 
be  much  larger  and  less  injurious  than  similar  quantities  given  by  the 
svstemic  circulation.  Toxicologists  also  recognize  the  filtering  influence 
of  the  liver,  in  that  poisons  may  be  recognized  in  that  organ  when  not 
discoverable  elsewhere.  Viola^  has  shown  that  in  pregnancy  the  anti- 
toxic function  of  the  liver — by  which  I  mean  its  poison-neutralizing 
property — is  lowered,  and  it  may  be  that  this  in  part  accounts  for  the 
intense  structural  changes  occurring  in  the  organs  in  the  toxemia  of 
pregnancy.  (See  p.  80.)  The  experiments  of  Brunton  and  Boken- 
ham"  clearly  establish  that  the  toxicity  of  the  poison  produced  by  the 
diphtheria  bacillus  is  lessened  by  passage  through  the  liver  or  contact 
with  the  expressed  juice  of  the  hepatic  cells.     The  modern  conception 

'  "Lo  Sperimentale.  "  IQ02. 

^  "Jour,  of  Path,  and   Bact.,"  Nov.,   igo4. 


i.ivi;r.  739 

of  ininuiiiity  (p.  99)  rests  u\)i.m  the  h_\-j)otliesis  that  poisons  are  anchored 
to  the  cells  upon  which  they  act,  and  the  well-known  fact  that  the  liver 
suffers  in  many  intoxications  can  be  adduced  as  pathologic  evidence 
in  support  of  the  view  that  the  organ  possesses  antitoxic  qualities. 
Padoa '  has  shown  that  not  only  does  the  liver  alter  toxin,  but  that  the 
organ,  in  accomjjlishing  this  function,  suffers  in  direct  proportion  to 
the  amount  of  toxin  which  it  anchors  or  transforms.  It  is  generally 
conceded  that  l)ile  is  bactericidal, — usually  to  a  higher  degree  than 
the  blood, — but  the  frequency  with  which  the  hepatic  ducts  and  gall- 
bladder are  infected  shows  conclusively  that  the  bacteriolytic  activity, 
like  similar  functions  in  other  organs  or  body-fiuids,  is  restricted. 

6.  Adipopcxic  fuuctioii:  That  the  liver  stores  fat  and  that  it  may 
manufacture  or  at  least  convert  fat  is  well  known.  We  do  not  know, 
however,  why,  in  certain  conditions,  the  fat  accumulates  in  the  liver 
far  in  excess  of  the  normal,  at  the  same  time  that  other  organs  and 
tissues  are  wasting. 

The  normal  weight  of  the  liver  varies  from  1200  to  1800  gm.  Its 
relative  weight  compared  with  that  of  the  body  is  slightly  less  in  the 
female  than  in  the  male.  According  to  Verraeck,  the  specific  gravity 
is  about  1.039;  ii"^  tuberculosis  it  may  be  reduced  to  1.020;  it  is  raised 
in  cirrhosis.  Postmortem  the  under  surface  of  the  liver  is  usually  dark- 
ened (pseudomelanosis)  from  contact  with  the  intestine  and  stomach. 
Gas-production  in  the  liver  (foam  liver  or  emphysematous  liver)  is 
occasionally  seen  at  autopsy.  The  cavities  are  usually  small;  the  cut 
surface  resembling  a  sponge.  The  condition  is  usually  due  to  the 
Bacillus  aerogenes  capsulatus  (p.  135)  and  occasionally  other  gas-pro- 
ducing organisms. 

Malpositions  of  the  liver  may  be  congenital  or  acquired;  when  the 
viscera  are  transposed,  the  liver  passes  to  the  left  side.  The  most  im- 
portant forms  of  malposition  are  acquired  and  are  classed  under  the 
term  hepatoptosis;-  mobile  liver,  floating  and  wandering  liver,  are 
names  also  used.  In  anteversion  the  anterior  border  passes  down- 
ward and  forward,  and  the  position  of  the  posterior  remains  unchanged 
or  rises.  The  oblique  displacement  consists  in  prolapse  of  the  left  lobe, 
the  right  remaining  in  place  or  descending  slightly.  In  total  tlisplace- 
ment  the  whole  organ  is  affected.  Anteversions  are  relatively  frerjuent. 
oblifjue  displacements  less  common,  and  total  prolajjse  rare.  Prolapse 
is  thought  by  some  to  favor  the  development  of  gall-stones;  of  the 
ninety  cases  of  hepatoptosis  collected  by  Judet,  cholelithiasis  was, 
present  in  fifteen.  Steele  has  shown  that  in  prolapsed  liver  the  pres- 
sure necessary  to  force  fluid  through  the  biliary  passages  ri.ses.  The 
liver  is  also  displaced  by  pressure  changes  on  either  side  of  the  diaphragm ; 
ascites  or  large  abdominal  tumors  force  the  organ  upward.  Pleural 
effusion,  hydrothorax,  and  tumors  affecting  the  right  pleura  or  lung,  dis- 
place the  organ  downward.  Abnormallv  large  livers  are  supposed  to 
drag  upon  the  diaj)hragm  and  sometimes  descend  without  altering  their 
relations  to  that   structure. 

Malformations  of  the  Liver,— Rarely  the  liver  is  absent;    somotim.-; 

'  "  Riv.  Crit.  di  (ilin.  Med.."  Sept.  and  Oct.,  1904. 

'Judet.  "Revue  de  Gyn  , "  Paris,  rgoi,  vol.  vi.  Steele,  "Univ.  of  I'enna. 
Med.  Bull.,'"  Jan..  1003.  p.  424.  Meyer,  "Berl.  klin  Woch.,"  1904,  No.  16.  Pren- 
tiss,  "Amer.   Jour,  o^  Obstet.,"  May,    1904. 


740 


SPECIAL   PATHOLOGY. 


it  is  miniature,  and  occasionally  the  left  lobe  is  the  largest.  Accessory 
lobes,  or  even  small  accessory  livers,  occur,  and  changes  in  the  posi- 
tion and  depth  of  the  tissues  are  not  exceedingly  rare.  Abnormal  lobes 
attached  by  a  pedicle  are  sometimes  found  in  hernial  sacs  at  the  um- 
bilicus; they  have  been  mistaken^  for  tumors  and  excised.  Tongue- 
like lobes  are  usually  acquired  and  the  result  of  constriction.  The 
liver  is  sometimes  divided  into  a  large  number  of  irregular  lobes;  Moser 
reported  a  case  in  which  there  were  sixteen;  some  such  organs  are  true 
malformations,  but  others  are  due  to  congenital  syphilis.  The  gall- 
bladder may  be  absent,  buried  in  the  liver  tissue,  and  is  occasionally 
directed  backward  instead  of  anteriorly.  The  biliary  passages^  are 
occasionally  impervious  and  sometimes  absent. 

Hyperemia  of  the  liver  is  physiologic  during  digestion,  and  by  some 
is  believed  to  be  a  constant  condition  in  diabetes. 

Chronic  congestion  of  the  liver ^  results  from  any  condition  that 
retards  the  venous  circulation  and  slows  the  blood  in  the  inferior  vena 
cava;  the  most  frequent  causes  of  this  condition  are  valvular  heart 
disease  (p.  518),  especially  mitral  disease,  and  pulmonary  obstruction, 
as  in  emphysema,  chronic  bronchitis,  etc.  The  retarded  circulation 
raises  the  pressure  in  the  thin-walled  hepatic  veins,  which,  being  most 
distensible  within  the  lobule,  gradually  dilate,  and  by  pressure,  and 
associated  malnutrition,  lead  to  atrophy  of  the  juxtaposed  liver-cells; 
the  zone  adjacent  to  the  hepatic  vein  is  first  affected,  and,  histologic- 
ally, may  be  composed  of  dilated  branches  of  the  hepatic  vein,  with 
complete  destruction  of  those  hepatic  cells  lying  immediately  around 
the  central  vessel.  The  retarded  circulation  favors  the  infiltration  of 
fat,  and  the  margin  of  the  lobule  may  contain  such  an  excess  of  this 
substance  that  it  appears  distinctly  yellow  to  the  naked  eye. 

Macroscopically,  the  organ  is  much  larger  than  normal,  and  may 
attain  considerable  size;  that  this  is  largely  a  vascular  distention  is 
shown  by  the  fact  that  when  the  veins  pulsate,  the  liver  may  also  mani- 
fest this  phenomenon.  The  organ  is  red,  hence  the  name,  red  atrophy, 
and,  on  section,  oozes  considerable  blood;  the  lobules  can  usually  be 
made  out,  and  the  dark-red  center  of  each  lobule,  with  its  lighter  per- 
iphery, resembles  a  transverse  section  of  a  nutmeg,  and  hence  the  name, 
nutmeg  liver.  In  some  cases  there  is  considerable  increase  in  the  con- 
nective tissue.  Pigmentation  is  almost  constantly  present;  the  granules 
are  red  or  brownish,  and  occupy  the  liver  cells  and  the  endothelium 
of  the  capillaries  and  lymphatics.  While  the  organ  during  life  may 
be  much  larger  than  normal,  when  removed  and  drained  of  blood  it 
shrinks  and  presents  a  wrinkled  capsule,  and  is  much  lighter  than  its 
antemortem  size  would  indicate. 

Occlusion  of  the  hepatic  artery*  or  its  branches  produces  necrosis 
in  the  liver  tissue,  although  the  process  is  not  that  of  a  typical  infarc- 
tion;   this  is   due   to   the   nutrition   supplied   by  the   branches   of   the 

>  Salvia,  "Revue  de  Chir.,"  Oct.,  1Q02.  Tuffier,  "Soc.  de  Chir.,"  July  22, 
tgo3:    "La  Presse  Med.,"  July  25,  1903,  p.  540. 

"^Ferguson,  "Amer.  Med.,"  Dec.  21,  iqoi.  Wollstein.  "Arch,  of  Pediatrics," 
March.  1902.  Kirmisson  and  Herbert,  "Societe  Anatomique."  March  27,  1903; 
"La   Presse  Med.,"  April   i.   1903.  p.   276.  1 

3  Hart,  "Zieg.  Beitr.,"  1904,  Bd.  xxv,  p.  303.  Creraudel,  'La  Presse  Med.," 
Dec.    3,    1904,   P-    769. 

*  Tischner,   "Virchow's  Arch.,"    1904,   Bd.   cLxxv,   p.   90. 


l.IVKk. 


741 


portal  vein.  In  Tischner's  exi)eriments  sometimes  one-third  to  one-half 
of  the  orj,'an  was  necrotic.  Accordinj,'  to  (irunert,'  tliere  are  thirty-five 
recorded  cases  of  aneurysm  of  tlie  hepatic  artery.  They  sometimes 
cause  jaundice  by  obstructing  the  bile-duct,  and  may  erode  the  liver, 
stomach,  or  duodenum,  and  into  the  last  two  cavities  they  occa- 
sionally rupture. 

Thrombosis  of  the  portal  vein'  is  .sometimes  observed  in  chronic 
obstruction,  but  is  usually  due  to  a  thromboj)hlcbitis  which  may  occlude 
one  or  more  branches  or  the  main  trunk  of  the  vessel.  Thrombo.sis 
occasionally  results  from  extension  of  neoplasms  from  the  stomach, 
intestines,  or  pancreas,  or  from  the  biliary  passages.  Infective  and 
suppurative  processes  involving  the  spleen,  intestine,  mesentery,  retro- 


\;-;:Hv.-^';'/      :      "    ■'■■  - 


y»r  ^.\ 


\      E 


I        B 


Fig.  321. — LivF.K.  .\i)\ w.  1  1.  imi.    \iKiiiiii. 
A .  Contral    vein  the  wall  of  which  conlains  red  cells,  and  at  B  pigmcntcfl  endothelial  cells.     C.  C.  Columns  of 
liver  cells.     D.  Dilated    intralobular  capillaries  distended  by  erythrocytes.     £.  In  this  area  the  columns  of 
hepatic  cells  have  largely  di.sapixrared  and  the  capillary  walls  have  wasted  or  been  absorljed. 


peritoneal  tissues,  or  bile-ducts,  and  especially  those  occurring  in  the 
appendicular  region,  may  be  attended  by  thrombosis  of  the  portal 
vein.  The  condition  is  occasionally  observed  in  typhoid;  the  throm- 
bus may  organize,  or  as  a  result  of  infection  undergo  necrosis;  either 
process  may  be  attended  by  the  formation  of  emboli  which  necessarily 
enter  the  liver.  Where  the  thrombus  gives  rise  to  obstruction,  there 
is  not  infrecjuently  an  intense  ascites.  In  the  case  reported  bv  Schulz 
and  MuUer  tapping  was  necessary  every  ten  to  fourteen  days.  The 
blood-supply  to    the   liver  afforded  by  the  hepatic  artt-rv  mav  prevent 

'"Deut.  Zeit.  f.  Chir  , "  Dec.   1903. 

-  Steinhaus.    "Deut.  Arch.  f.  klin.  Med.."  igo^,  Nos.  3  ami  4,  p.  3O4.     Gerster, 
"Trans.  Anier.  Surg   Assoc."  1903. 


742  SPECIAL  PATHOLOGY. 

any  important  structural  changes  in  the  hepatic  tissue.  In  some  cases 
fibrous  hyperplasia  and  occlusion  of  the  intrahepatic  portal  branches 
occur. 

Typical  infarction  of  the  liver/  identical  with  that  observed  in  other 
organs,  is  exceedingly  rare.  Hepatic  infarcts  may  be  produced  by 
thrombosis,  embolism,  or  occlusion  affecting  the  portal  vein,  hepatic 
artery,  or  hepatic  vein.  An  essentially  similar  condition  results  from 
laceration  of  the  hepatic  tissue  with  or  without  rupture  of  the  capsule. 
Hepatic  infarction  appears  to  be  more  frequent  after  occlusion  of  the 
artery  than  the  vein,  and  in  this  form  the  necrosis  is  anemic  rather  than 
hemorrhagic.  The  studies  of  Zahn  and  Chiari  indicate  that  a  form 
of  hemorrhagic  infarction  called  atrophic  is  most  commonly  produced 
by  portal  embolism,  although  Steinhaus  has  shown  that  it  may  result 
from  occlusion  of  the  hepatic  artery.  The  areas  of  necrosis  are  usually 
irregular,  marginated  by  a  zone  of  reactionary  inflammation  and  attempts 
at  repair;  smaller  multiple  infarcts  give  rise  to  miliary  necroses  which 
later  are  infiltrated  by  leukocytes,  and  if  not  infected,  form  nodules 
of  fibrous  tissue.  Some  efforts  at  hepatic  regeneration  can  occasion- 
ally be  recognized.  The  suppurative  lesions  following  infarction  will  be 
discussed  with  hepatic  abscess.  It  is  evident  that  embolic  phenomena 
frequently  involve  the  liver  without  producing  necrosis.  I  have  on 
more  than  one  occasion  observed  neoplastic  emboli  in  the  hepatic 
tissue  when  even  microscopic  necrosis  was  absent. 

Hypertrophy  of  the  liver  is  infrequent  except  as  a  compensatory 
process.  When  one  lobe  or  one  part  of  a  lobe  is  destroyed  by  trauma 
or  disease,  increase  in  the  amount  of  the  residual  hepatic  structure  is 
usually  observed;  thus,  in  atrophy  of  one  lobe  or  a  part  of  a  lobe  as 
a  result  of  pressure,  or  in  destruction  of  one  lobe  by  abscess  or  cyst, 
if  the  patient  fully  recovers,  hypertrophy  of  the  remaining  liver  tissue 
may  occur.  Regenerative  effort  can  often  be  recognized  in  the  hepatic 
tissue;  it  is  characterized  by  proliferation  of  the  hepatic  cells  in  which 
karyokinetic  figures  can  frequently  be  recognized.  The  new  cells  are 
rarely  assembled  in  the  histologic  order  of  the  normal  liver. 

Atrophy  of  the  liver  arises  from  several  causes: 

Simple  atrophy  of  the  liver,  due  to  starvation  or  inanition:  e.  g., 
in  the  writer's  collection  is  a  liver  weighing  about  560  gm.,  taken  from 
a  patient  who  died  slowly,  from  starvation,  as  the  result  of  cancer  of 
the  esophagus.  In  such  cases,  associated  with  general  atrophy,  the  liver 
may  be  reduced  to  one-third  of  its  normal  dimensions  and  weight.  The 
process  is  probably  both  simple  and  numeric,  and  begins  at  the  periph- 
ery, where  the  evidences  are  most  marked;  every  part  of  the  organ, 
however,  is  implicated. 

Morbid  Anatomy. — Such  a  liver  possesses  a  sharp  margin,  and  is 
darker  in  color  than  the  normal  organ;  the  relation  of  lobes,  one  to 
another,  is  normal;  after  removal  from  the  body  and  when  drained 
of  its  blood,  the  capsule  is  wrinkled,  because  the  remaining  liver-cells 
no  longer  fill  it ;  the  gall-bladder  frequently  projects  from  three  to  seven 
centimeters   beyond   the    hepatic   margin,      The    blood-supply   to    the 

*  Longcope,  "Univ.  of  Penna.  Med.  Bull.,"  Aug.,  1901.  Baldwin,  'Jour. 
Med.  Research,"  1902,  vol.  viii.  See  also  Tischner,  "Virchow's  Arch.,"  1904, 
Bd.  clxxv,  p.  90;  and  Steinhatis,  "Deut.  Arch.  f.  klin.  Med.,"  1904,  Nos.  3  and  4, 
p. 364. 


LIVHK.  743 

organ  is  poor  in  nutrition,  the  absence  of  food  from  the  alimentary 
canal  excludes  the  normal  stimulus  to  secretion,  and,  as  a  result  of  the 
combined  conditions,  very  little  bile  is  produced.  Histologically,  re- 
duction in  the  size  of  the  lobules  is  extremely  marked;  the  liver  cells 
are  small,  atrophied,  usually  stain  indifTerently,  and  are  frefjuently 
pigmented;  there  seems  to  be  as  much  fibrous  tissue  as  liver  structure, 
but  this  is  probably  due,  not  to  an  increase  of  hbrous  elements,  but  to 
a  diminution  in  the  size  and  number  of  the  hepatic  cells. 

Pressure  atrophy  of  the  liver  covers  a  multitude  of  lesions.  Women 
who  lace  tightly,  b\-  i)rcssing  in  the  margin  of  the  ribs,  produce  a  deep 
groove  or  impression  in  the  larger  lobe  of  the  liver,  and  may  almost 
completely  divide  it;  the  same  result  is  accomplished  in  men  who  wear 
tight  belts,  as  is  so  frequently  done  by  certain  classes  of  laborers.  The 
liver  is  verv  susceptible  to  pressure,  and  is,  therefore,  influenced  by 
neoplasms  in  adjacent  organs,  and  by  tumors  and  collections  of  gall- 
stones or  accumulated  secretion  or  inflammatory  matter  in  the  gall- 
bladder. 

Another  form  of  atrophy  from  pressure  is  red  atrophy,  which  has 
already  been  discussed;  in  this  condition  the  pressure  is  exerted  by 
the  blood  retarded  in  the  liver  lobule,  thus  compressing  the  cells  and 
leading  to  their  disappearance.     (See  Congestion  of  the  Liver,  p.  740) 

A  certain  amount  of  atrophy  accompanies  amyloid  infiltration,  in 
that  the  new  deposit  in  the  liver  interferes  to  a  variable  extent  \\-ith 
the  function  of  the  adjacent  cells.  The  older  view  that  the  evident 
wasting  of  the  hepatic  cells  in  cirrhosis  was  due  to  pressure  is  no  longer 
insisted  upon;  the  prevailing  belief  is  that  cellular  necrosis  and  fibrous 
hyperplasia  are  due  to  the  same  cause,  and  that  contraction  is  not 
an  important  element  in  the  production  of  atrophy.  Obstruction  to 
the  bile-ducts  is  followed  by  necrosis  of  the  liver  cells,  pigmentation 
of  the  organ,  and  atrophy  of  the  parenchyma;  the  liver  not  infrequently 
appears  large,  but  the  increased  size  is  due  to  connective-tissue  hyper- 
plasia, swelling,  and  changes  in  the  bile-ducts.  (See  Cirrhosis.)  Ob- 
structed bile-ducts  give  rise  to  pigmentation  and  atrophy  of  some  of 
the  cells.  In  all  forms  of  atrophy  of  the  liver  more  or  less  pigmenta- 
tion of  the  organ  is  commonly  present;  besides  the  pigmentation  in- 
cident to  atrophy,  the  lesion  itself  interferes  with  the  production,  and 
mav  also  obstruct  the  escape  of  the  bile  (acute  yellcnu  atrophy).  (See 
p.  747,  also  Jaundice,  p.  234.) 

Infiltrations  to  which  the  liver  is  liable  are:  (i)  Fatty  infiltration, 
(2)  amvloid  infiltration,  and  (3)  pigmentary  infiltration. 

Fatty  infiltration  of  the  liver  arises  as  the  result  of  an  abundance 
of  fat.  sugar,  or  .ilcohol  supplied  to  the  organ;  in  all  of  which  cases 
the  liver  acts  merely  as  a  storehouse  for  the  temporary  deposit  of  the 
nutrient  element  not  needed  by  the  system  at  large:  a  certain  amount 
of  fat  is  normal,  and  is  essential  to  the  elaboration  of  perfect  bile.  Those 
causes  just  cited  represent  nothing  but  an  excess  of  the  normal. 

Fattv  infiltration  of  the  liver  is  also  observed  in  those  diseases 
in  which  oxidation  is  in  abeyance.  As  an  example  of  this  form  may 
be  mentioned  the  fatty  infiltration  found  in  consumption,  cachexia, 
anemia,  and  allied  conditions.  The  .slowed  circulation  in  chronic  conges- 
tion is  probably  the  cause  of  the  fatty  infiltration  accompanying  the 
condition.      In    certain    forms    of    cirrhosis,    particularly   that    due    to 


'44 


SPECIAL   PATHOLOGY 


alcohol,  considerable  fat  is  usually  present  in  the  liver  lobule,  and  the 
color  of  the  organ  is  largely  due  to  the  presence  of  this  body.  The 
lesion  produced  by  phosphorus-poisoning  is  held  by  some  to  be  a  fatty 
infiltration,  and  by  others  a  fatty  degeneration;  it  is  possibly  a  com- 
bination of  the  two  processes. 

Morbid  Anatomy. — The  liver  of  fatty  infiltration  is  sometimes  enor- 
mously increased  in  size,  and  is  usually  the  largest  liver  seen  in  the  post- 
mortem room ;  it  is  firm,  the  margin  rounded,  its  capsule  smooth,  pale  in 
color,  bloodless,  even  on  section,  and  when  incised  with  a  moist,  clean 
knife,  distinctly  greases  the  blade.  While  the  organ  may  weigh  from 
three  to  four  kilograms,  its  specific  gravity  is  low,  owing  to  the  amount 
of  fat  which  it  contains;    the  added  fat  being  lighter  than  water,  the 


^"^  •i:'<'''X'*'^  '^X'-  '■. ." '-^>? :-';'  .r\^^^ 


Fig.  362. — Liver,  Cirrhosis  .\nd  Marked  Fatty  Infiltration. 
Death  was  the  result  of  croupous  pneumonia,  and,  therefore,  an  added  granular  degeneration  (cloudy  swelling) 
of  the  few  p^e^•iously  unaltered  liver  cells  is  also  present.     .4,  .4.  Groups  of  granular  liver  cells.     B.  Liver 
cell,  the  protoplasm  of  which  is  almost  completely  replaced  by  fat.     C.  Imperfectly  outlined  bile-duct.     D. 
Branch  of  i»rtal  vein  surrounded  by  the  newly  formed  fibrous  tissue. 

organ  may  possess  a  specific  gravity  of  looo.  The  gall-bladder  does  not 
extend  to  the  margin  of  the  organ;  the  bile  is  usually  lighter  in  color 
than  the  normal,  but  clinically  there  is  no  evidence,  in  ordinarily  fatty 
livers,  that  the  bile  is  deficient  in  functional  activity. 

Morbid  Histology. — In  the  earlier  stages  of  fatty  infiltration  the  fat 
is  most  abundant  in  the  periphery  of  the  liver  lobule,  occupying  largely 
the  portal  vein  zone;  in  extremely  advanced  cases  the  infiltrated  area 
may  approach  the  center  of  the  lobule,  but  not  until  the  margin  is  ex- 
tensively invaded.  As  a  rule,  the  fat  exists  as  a  single  large  globule 
in  the  liver  cell,  crowding  the  nucleus  to  one  side;  the  nucleus  fre- 
quently appears  normal  in  structure  and  in  stain  reaction.  Liver 
cells  adjoining  those  containing  large  quantities  of  oil  are,  as  a  rule, 


L I  \'  K  k . 


■45 


uninvolved;  granular  or  cloudy  change  in  the  unatTected  cells  is  rarely 
present,  a  fact  of  considerable  value  in  differentiating  the  liver  cell  of 
fatty  infiltration  from  the  same  structure  in  fatty  degeneration.  (See 
Fatty  Infiltration,  p.  224.) 

Lardaceous  disease  of  the  liver  is  manifested  by  an  inliltration  into 
the  t)ri:an  of  a  peculiar  body,  called  lardacein.  (See  p.  22S.)  The  in- 
filtrated substance  is  initially  de])Osited  in  the  intermediate  or  hepatic 
artery  zone  of  the  liver  lobule;  the  causes  are  those  of  amyloid  infil- 
tration in  general. 

XlorhiJ  Anatomy. — The  tvpic  amyloid  liver  is  very  much  increased 
in  size,  its  margin  rounded,  and  the  capsule  smooth  and  free  from 
thickening;    the  tissue  is  firmer  and  more  elastic  than  normal,  contains 


Fig.  563. — Liver.  F,urly  .•Vdvanckd  Laroackois  Disease.     (The  ortjan  wciglicil   i;  pounds.) 
A.  Ccmral  vcssjI  of  lobule  surrounded  l>y  con.siderablc  residual  liver  (issue;  ihe  periphery  of  the  lobule  with  corre- 
sponding parts  of  adjacent  lobules  al.so  persists.     B,  B.  Lardacein.     C".  Interlobular  ves.sel. 


little  fat,  and  is  pale  and  bloodless;  the  cut  surface  responds  to  the 
chemic  and  stain  reactions  commonly  given  by  amyloid  material.  (See 
p.  230.)  Amvloid  infiltration  not  infrequently  involves  livers  in  which 
other  processes  militate  against  great  enlargement,  or  the  lardaceous 
deposit  is  sometimes  scanty  and  not  widely  distributed;  in  either  case 
the  organ  is  not  consj»icuously  enlarged,  or  often  is  normal  in  size; 
cirrhotic  livers  containing  traces  of  lardacein  may  be  small. 

Properlv  prepared  sections  show  the  lardaceous  material  more  or 
less  irregularlv  distributed  in  the  intermediate  or  hepatic  artery  zone 
of  the  liver  lobule.  The  branches  of  the  hepatic  artery  manifest  the 
usual  lardaceous  deposit  in  their  walls. 

Pigmentary  infiltration  of  the  liver  occurs  in  connection  with  chronic 


746  SPECIAL  PATHOLOGY. 

malaria,  and  is  associated  with  other  lesions  that  give  the  organ  the 
name  of  malarial  liver.  The  cause  of  the  process  evidently  lies  in  two 
conditions:  (i)  The  repeated  engorgement  occurring  as  a  result  of  the 
malarial  paroxysm,  the  liver  being  enormously  distended  with  blood 
at  each  chill;  and  (2)  the  hematolytic  changes,  induced  by  the  malaria 
parasite,  liberates  the  coloring-matter  (hemoglobin),  which,  after  im- 
portant alterations,  is  finally  deposited  in  the  hepatic  tissues.  The 
pigment  liberated  by  rupture  of  the  red  blood-cell  containing  sporulat- 
ing  hematozoon  is  taken  up  by  phagocytic  white  cells  (melaniferous 
leukocytes,  see  pp.  191  and  413),  which  deposit  it  in  the  organs.  The 
granules  are  often  found  in  the  endothelial  cells  of  the  lymph-  and 
blood-vessels,  free  in  the  interstitial  spaces,  and  also  within  the  liver 
cells.  Craig^  observed  melaniferous  leukocytes  in  the  capillaries  of  the 
liver  and  also  white  blood-cells  containing  bodies  resembling  degenerated 
parasites  of  malaria.  As  hemolysis  is  excessive  and  conversion  of  blood- 
pigment  into  bile  imperfectly  performed  in  malaria,  the  pigmentation 
may  be,  in  part  at  least,  the  result  of  functional  inactivity  of  the  hepatic 
cell.  When  the  condition  has  persisted  for  any  length  of  time,  increase 
in  the  connective  tissue  of  the  organ  is  sometimes  observed.  Another 
form  of  hepatic  pigmentation  in  which  the  coloring-matter  is  derived 
from  the  blood  is  seen  in  hemochromatosis  (p.  234). 

In  pigmentary  infiltrations  of  the  mucous  membranes,  and  especially 
of  the  lungs,  such  as  anthracosis,  the  pigment,  entering  the  blood  from 
lymph-nodes  which  have  ruptured  into  a  vein,  reaches  the  liver  and 
is  deposited  in  the  connective  tissue  that  surrounds  the  hepatic  vessels, 
giving  rise  to  a  certain  amount  of  pigmentation  of  the  organ.  (See 
Pigmentary  Infiltration,  p.  231.) 

Morbid  Anatomy. — During  life,  when  distended  by  blood,  and  when 
the  process  is  not  combined  with  cirrhosis,  the  organ  is  larger  than  nor- 
mal; postmortem,  it  is  usually  smaller,  but  the  rounded  margin  and 
wrinkled  capsule  indicate  that  the  shrinking  has  been  a  postmortem 
process.  Usually,  the  wrinkled  surface  can  be  rendered  smooth  by 
stretching.  The  color,  due  to  the  deposited  pigment,  is  grayish-brown 
or  slaty;  this  grayish,  lusterless,  lead  color  justifies  the  name  slate- 
colored  liver,  sometimes  given  to  the  organ.  The  liver  is  more  or  less 
flabbv  or  flaccid,  resists  incision  more  than  the  normal  organ,  and,  on 
section,  oozes  considerable  blood  and  pigmented  serum;  the  gall- 
bladder is  small  and  does  not  extend  to  the  margin  of  the  liver;  the 
contained  bile  is  commonly  tarry  or  thick  and  ropy.  Under  the  micro- 
scope a  blackish  or  brownish  pigment  is  found  disseminated  throughout 
the  organ,  around  the  lobules,  and  in  the  perivascular  intralobular 
structures;  this  is  altered  blood  coloring-matter  (melanin).  Associated 
with  the  pigment  deposit  a  considerable  increase  in  the  connective 
tissue  is  usually  observed ;  this  may  be  so  ■  great  as  to  constitute  an 
actual  cirrhosis;  the  newly  formed  connective  tissue  is  found  not  only 
in  the  interstitial  structures  around  the  lobules,  but  in  the  intralobular 
reticulum  as  well. 

The  foregoing  description  applies  particularly  to  the  hepatic  enlarge- 
ment of  chronic  malaria.  If  death  occur  early  in  the  infection, 
pigmentation  is,  of  course,  less  marked.  The  malaria  parasites  may 
be  present  in  the  organ,  particularly  in  the  estivo-autumnal  fever. 
1  "Amer.   Med.,"  July   25,    1903,  p.    145. 


i.ivhk.  747 

Necrotic  areas  associated  with,  or  independent  ol,  caj)illary  thrombosis 
are  occasionally  observed. 

The  degenerations  most  frequent  in  the  liver  are  parenchymatous 
and  fatty. 

Parenchymatous  degeneration  of  the  liver  is  found  in  connection 
with  high  temperatures,  septic  and  other  infectious  processes,  and  in 
many  intoxications.  (See  p.  241.)  The  organ  is  swollen,  is  usually 
pale.'  and  the  cut  surface  is  cloudy  and  opaque,  not  shining  and  trans- 
lucent, like  the  normal;  with  the  granular  change  in  the  epithelium  of 
the  lobules  there  is  not  infrefjuently  more  or  less  necrosis,  usually  coagu- 
lative  in  character.  The  bile  elaborated  by  such  an  organ  is  deficient 
in  quantity  and  may  be  physiologically  inert.  The  affected  liver-cells 
are  granular  (Fig.  140,  p.  242)  and  show  the  initial  changes  observed 
in  the  first  stage  of  fatty  degeneration.  By  some  it  is  believed  that 
the  structural  alteration  is  essentially  similar  to  that  of  beginning 
catarrhal  inflammation  of  the  lobule,  analogous  to  the  lesion  observed 
on  the  mucous  surfaces  in  the  stage  of  catarrhal  inflammation  when 
desquamation  is  impending;  the  belief  that  the  degenerative  and  ne- 
crotic changes  constitute  a  part  of  an  inflammaton.'  process  has  led  to 
the  condition  under  consideration  being  called  parenchymatous  hepa- 
titis. The  process  is  of  a  type  justifying  the  conviction  that  it  is  in- 
flammatory, and  in  some  respects  more  closely  resembles  the  necroses; 
like  the  latter,  it  may  be  appropriately  regarded  as  a  sequence  of  the 
toxic  action  of  poisons  brought  to  the  liver  by  the  circulating  blood. 

Acute  yellow  atrophy  of  the  liver/  also  known  as  malignant  jaundice, 
icterus  gravis,  essential  hemorrhagic  icterus,  and  acute  fatty  degenera- 
tion of  the  liver,  are  names  applied  to  an  obscure  affection  about  the 
etiologv  of  which  we  are  in  doubt.  The  exact  character  of  the  changes 
observed  also  remains  undetermined;  Taylor's  studies  indicate  that, 
at  least  in  some  cases,  the  fat-content  of  the  organ  is  not  increased,  and 
that,  therefore,  it  is  not  a  fatty  degeneration.  Many  who  investigated 
the  condition  believe  that  it  is  primarily  a  necrosis,  and  with  this  view 
I  am  inclined  to  agree.  The  name  acute  yellow  atrophy  is  noncom- 
mittal, describes  the  common  anatomic  manifestations,  and  does  not 
indicate  the  process  by  which  the  change  occurs. 

The  cause  of  this  condition  is  not  known,  but  the  feeble  tendency 
toepidemicity,and  the  fact  that  the  etiologic  agent  attacks  individuals 
in  groups. — among  pregnant  women  many  cases  may  occur  in  a  single 
locality. — taken  with  the  character  of  the  symptoms  and  lesions,  indi- 
cate a  possible  infectious  agent.  A  similar  condition  has  been  produced 
in  animals  by  bacterial  toxins,  and  bacteria  are  frequently  observed 
in  the  affected  organs.  I  believe  all  investigators  agree  that  the  dis- 
ease is  of  toxic  origin,  although  unanimity  as  to  the  character  and  source 
of  the  toxic  body  is  wanting.  It  has  been  observed  after  chloroform 
anesthesia,  particularly  in  children,  but  Guthrie  believes  that  some 
antecedent  condition  determines  its  occurrence  and  that  it  is  not  directly 

'  MacCallum,  "  Johns  Hopkins  Hospital  Reports,"  1^02.  vol.  x.  Taylor, 
•  Jour,  of  Med.  Research.'  1002.  vol.  viii.  p.  424.  Guthrie.  "Lancet."'  Jan.  27 
and  Feb.  3,  1804,  pp.  105  and  si;?.  and  "Lancet."  Julv  4.  1Q03.  p.  10.  Cohn. 
•Zentralbi.  f.  Gvnak.."  Oct.  S.  1004.  No.  34.  De  Paoli  and  Pietro,  "Arch.  f.  G\ti.." 
1904.  Bd.  Ixxiii'.  p.  357.  Wells  and  Bassoe.  "Jour.  Annr  M-'i  Assoc."  March 
4.    1905.  p.  6.S5. 


748  SPECIAL   PATHOLOGY. 

the  result  of  the  anesthetic.  The  disease  is  most  common  m  women, 
especially  during  the  puerperium,  and  usually  occurs  between  the  ages 
of  twenty  and  thirty.  As  before  stated,  the  changes  induced  by  phos- 
phorus and  arsenic  are  analogous,  but  not  always  identical.  Some  ob- 
seryers  are  inclined  to  regard  the  process  as  inflammatory;  others, 
as  a  purely  degenerative  change  secondary  to  necrosis  of  hepatic  tissue 
produced  by  a  poison  the  exact  nature  of  which  is  unknown. 

Morbid  Anatomy. — In  typic  cases  the  organ  is  much  reduced  in  size 
and  weight,  is  flabby,  and,  when  the  change  is  advanced,  can  be  folded 
over  upon  itself;  as  a  whole,  the  consistence  may  be  almost  that  of  a 
bag  of  fluid — semifluctuating ;  the  capsule  is  wrinkled.  The  color  is 
not  uniform;  on  the  surface  and  on  section  dirty  yellow  areas,  varying 
in  size  and  irregular  in  form,  are  often  conspicuous;  around  and  between 
these  patches  the  liver  is  red,  cloudy,  and  frequently  distinctly  firmer. 
While  the  organ  occasionally  resists  incision,  the  semifluid  condition 
of  its  contents  is  shown  by  the  fact  that  large  quantities  of  hepatic 
tissue  may  be  extruded  through  a  small  opening.  There  may  be  hemor- 
rhage into  the  organ,  although  this  is  more  common  in  other  viscera 
than  in  the  diseased  liver.  The  myocardium  is  usually  soft,  granular, 
or  fatty,  and  hemorrhages  into  the  muscle  or  beneath  the  pericardium 
or  endocardium  are  usually  present.  Necroses  and  infarction  are  com- 
mon in  the  spleen;  the  renal  epithelium  is  usually  granular  or  fatty, 
and  desquamating,  and  sometimes  a  marked  acute  diffuse  nephritis  is 
present. 

Under  the  microscope  the  changes  to  be  observed  are  most  intense 
in  the  yellowish  areas  already  described.  The  liver-cells  are  indistinct 
in  outline  and  often  extremely  fatty;  all  stages  of  fatty  degeneration 
are  recognizable;  cloudy  and  granular  cells  and  cells  containing  minute 
oil-globules  abound,  and  occasionally  areas  occur  in  which  the  cells 
are  no  longer  demonstrable.  The  fat  seen  in  the  liver  cell  is  both 
within  and  around  the  nucleus,  and  sometimes  exists  as  minute  granules 
or  oil-globules,  in  contradistinction  to  the  large  drops  usually  present 
in  fatty  infiltration;  these  differentiating  points,  however,  are  not 
trustworthy.  The  evidences  of  nuclear  fragmentation  and  cell-necrosis 
are  not  present  in  simple  uncomplicated  fatty  infiltration.  All  zones 
of  the  liver  lobule  are  invaded  in  rapid  succession,  apparently  the  outer 
or  portal  vein  zone  first.  In  some  cases  the  connective  tissue  between 
the  lobules  is  normal;  in  others  it  shows  a  tendency  toward  prolifera- 
tion. 

Coagulation  necrosis,  as  seen  in  the  liver,  occurs  in  typhoid  fever, 
diphtheria,  and  allied  infectious  processes.  It  can  be  produced  by 
bacterial  toxins,  especially  those  of  the  diphtheria  bacillus,  and  by 
abrin  and  ricin.  Boxmeyer  ^  has  studied  the  hepatic  necroses  produced 
by  hog-cholera  bacilli,  and  concludes  that  the  lesions  are  of  two  kinds: 
one  is  produced  by  plugging  of  the  capillaries  by  large  mononuclear 
cells  and  the  direct  action  of  the  toxin;  the  other  results  from  hyaline 
thrombi  in  the  smaller  veins.  Pearce'  suggests  that  thrombi  may 
result  from  agglutinins  within  the  blood — the  agglutinin  thrombi  orig- 
inally described   by  Flexner.      Opie,^  in   studying  necrosis   within   the 

'  "Jour,  of  Med.  Research,"  March,  1903,  p.   146. 

^"Albany   Med.   Annals,"   Dec,    1004. 

•''  "Jonr  of  Med.  Research,"  July,   1904.  p.   147. 


LIVKK.  749 

liver  lobule,  fouml  that  they  ini^'ht  be  central,  peripheral,  or  in  tiie  mid- 
zone.  The  periphery  of  the  lobule  was  the  least  frequently  affected. 
The  hepatic  necroses  accompanying^  eclampsia'  are  rej^arded  by  many 
observers  as  the  most  constant  lesions  of  the  disease.  Prolonged  blood 
stasis,  infarction,  injury,  biliary  obstruction,  and  direct  infection  of 
the  hepatic  tissue  \:,\ve  rise  to  necrosis.  The  focal  necroses  include  ihose 
due  to  bacterial  toxins,  and  occur  in  organs  already  the  seat  of  cloudy 
swelling;  the  necrotic  areas  are  minute,  white  or  yellowish-white  in 
color,  cloudy,  and  oi)a(iue.  Histologically  the  liver  cells  rapidly  dis- 
appear and  are  replaced  by  a  hyaline  matrix  in  which  are  fragments 
of  nuclei  and  homogeneous,  degenerated,  or  necrotic  protoplasm.  Little 
is  known  with  regard  to  the  ultimate  fate  of  these  areas  in  patients  who 
recover.  Reed  has  described  fibroid  nodules  that  could  have  had  such 
an  origin,  and  a  number  of  investigators  have  suggested  that  the  con- 
dition might  give  rise  to  cirrhosis.  In  eclampsia,  in  addition  to  the 
necr(isis,  minute  hemorrhages  are  usually  present. 

Hepatitis  (inflammation  of  the  liver),  like  nephritis,  does  not  yield 
itself  to  svstematic  classification.  By  some  observers  the  conditions 
called  cloudv  swelling  and  acute  yellow  atrophy  are  classed  with  in- 
flammations of  the  organ  and  constitute  different  phases  of  what  is 
termed  acute  parenchymatous  or  nonsuppurative  hepatitis.  Klein  de- 
scribed an  acute  inflammatory  affection  of  the  liver  analogous  to  acute 
diffuse  nephritis,  and  Remlinger,  Jaboulay,  and  others  speak  of  an  acute 
swelling  of  the  liver  associated  with  splenic  enlargement  which  they  call 
acute  infectious  liver.  Of  these  conditions  our  information  is  too  in- 
definite to  justify  specific  statements  as  to  their  essential  nature,  etiol- 
ogy, or  pathology.  Clinically  and  anatomically  we  may  recognize — 
(ij  suppurative  inflammations  of  the  liver  and  (2)  chronic  processes 
attended  bv  the  production  of  an  excess  of  fibrous  tissue  and  ordinarily 
called  cirrhoses. 

Suppurative  hepatitis  or  hepatic  abscess  may  be  acute  or  chronic 
and  results  from  bacteria  entering — (i)  from  contiguous  structures.  (2) 
bv  the  portal  vein.  (3)  by  the  hepatic  artery,  (4)  by  the  biliary  chan- 
nels; (5)  traumatic  abscess,  the  path  of  infection  being  uncertain, 
and  (6)  amebic  abscess,  in  which  the  causative  factor  (amebae)  probably 
enters  the  liver  by  the  portal  vein;  the  distinctive  etiology  and 
pathologv  justify  a  separate  consideration  of  this  lesion.  The  suppura- 
tive lesions  due  to  infection  by  the  portal  vein  and  hepatic  artery  may 
convenientlv  be  considered  together  as  metastatic  abscesses.  Ulcers 
and  carcinoma  involving  the  stomach  may  penetrate  and  infect  the 
liver,  producing  a  slowly  advancing  suppurative  lesion  which  forms  the 
base  of  the  ulcerative  process.  Abscess  beneath  the  diaphragm,  empye- 
mata.  and  perinephric  suppurations  occasionally  extend  into  the  liver. 
F'ish-bones.  pins,  needles,  and  other  foreign  bodies  may  penetrate  the 
liver  from   the  stomach,  duodenum,  or  colon. 

Metastatic  abscess  due  to  infection,  primary  in  the  portal  area,  results 
from  a  pyelophlebitis  (p.  741)  in  which  pyogenic  bacteria  are  present. 
Such  abscesses  are  practically  always  secondary  to  primary  suppurative 
processes  involving  the  intestine,  appendix,  rectum,  pelvic  viscera, 
or  spleen.       Rolleston  states  that  such  infection  is  most  frequent  in 

'  Gilman.  Boston  Med.  and  Surg.  Jour..'  March  30.  1905.  p.  367:  also  Ewing. 
•' Amer.  Jour,  of  Obstct.."'  Feb..  1905. 


■5° 


SPECIAL  PATHOLOGY 


appendicitis,  and  Thompson  found  portal  infection  in  29  of  669  autop- 
sies following  appendicitis.  In  such  cases  the  liver  practically  always 
contains  abscesses,  which  are  not  invariably  of  the  same  size  or  age, 
and,  in  the  latter  instance,  represent  succeeding  embolisms.  The  ab- 
scess cavities  are  most  numerous  in  the  right  lobe;  the  condition  is 
usually  fatal.  When  the  infection  is  embolic  by  way  of  the  hepatic 
artery,  the  emboli  are  usually  smaller,  the  distribution  wider,  the  num- 
ber oi  abscesses  greater,  and  each  pus  collection  usually  minute,  some- 
times microscopic.  As  this  form  of  hepatic  suppuration  usually  accom- 
panies pvemia,  the  lesions  are  called  pyemic  abscesses.  When  such  a 
collection  attains  a  recognizable  size,  it  is  usually  from  confluence  of 
adjacent  foci.  The  affected  liver  is  enlarged,  cloudy,  and  hyperemic; 
in  typical  cases  the  abscesses  may  resemble  miliary  tubercles  (miliary 
abscess  of  the  liver),  but  are  soft,  and  the  extruded  pus  is  unlike  the 
caseous  material  occurring  in  tuberculosis.  Rarely  the  abscess  is  large. 
The  collections  of  pus,  when  the  infection  results  from  thrombophlebitis, 
are  usuallv  larger,  probably  because  the  emboli  are  grosser,  or  propaga- 
tion in  the  intrahepatic  branches  of  the  portal  vein  occurs  more  readily 
than  in  the  hepatic  artery. 

Hepatic  abscess  may  be  secondary  to  infection  traveling  by  the 
bile-ducts,  usually  a  suppurative  cholangitis,  which  will  be  found  de- 
scribed under  Diseases  of  the  Biliary  Passages.  The  abscesses  are 
multiple  and  are  often  difficult  to  differentiate  from  the  metastatic 
form.  Usually  the  pus  is  more  intensely  bile  stained,  and  w^hen  sec- 
tions of  the  hepatic  tissue  are  examined  microscopically,  it  can  be  ob- 
served that  the  infection,  in  the  smaller  abscesses,  has  extended  from 
the  bile-ducts.  The  difficulty  in  identif3dng  the  processes  is  further 
increased  bv  the  fact  that  abscesses  from  other  causes  may  penetrate 
the  ducts  and  give  rise  to  a  suppurative  cholangitis,  which  in  turn  may 
induce  new  centers  of  suppuration. 

Traumatic  abscess  of  the  liver  results  from  injury,  either  direct  or 
by  transmitted  force;  blows  on  the  abdominal  wall,  falls,  bumper,  and 
similar  accidents  induce  subcapsular  or  deeper  lacerations  in  the  organ, 
and  these  aft'ord  opportunities  for  the  colonization  of  bacteria  brought 
to  the  liver  by  the  blood.  Cysts,  quiescent  gummata,  and  tuberculous 
nodules,  or  obsolescent  areas  of  old  infection,  readily  suppurate  when  in- 
jured. Traumatic  abscess  is  usually  solitary,  and  at  most  but  two  or 
three  foci  are  found.  The  pus  is  frequently  loaded  with  bacteria, 
commonlv  bile  stained  and  sharph^  demarcated  from  the  contiguous 
liver  tissue,  which,  however,  is  the  seat  of  more  or  less  reactionary  in- 
flammation. Hepatic  suppuration  due  to  injury  is  usually  situated 
in  the  right  lobe  near  the  superior  surface.  When  the  lesion  is  due  to 
penetrating  wounds,  the  position  of  the  injury  determines  the  location 
of  the  abscess. 

Amebic  abscess  of  the  liver  ^  is  practically  always  a  complication  of 
dysenterv;  a  few  reported  instances  in  which  the  dysentery  apparently 
f  olio  wed  the  abscess,  or  was  absent,  must  be  supported  by  further  ob- 
servation before  we  are  justified  in  concluding  that  this  form  of  hepatic 
abscess  arises  independently  of  intestinal  amebiasis.  The  condition 
is  so  much  more  frequent  in  hot  than  in  temperate  climates   that  it 

1  See  references  to  Dysentery,  p.  726,  description  of  ameb£e,  p.  iSi:  also 
Rolleston,  "Diseases  of  the  Liver,"  1905,  p.   120. 


I.INKK. 


•51 


D 


is  sometimes  called  tropic  abscess.  In  alxjut  seventy-live  ])er  eent.  of  the 
cases  the  abscess  is  solitary;  two  are  present  in  ten  per  cent.,  and  more 
than  two  in  fifteen  jjer  cent.;  seventy-five  i^er  cent,  to  eighty  per  cent, 
of  the  absce.sses  are  situated  in  the  right  lobe.  It  has  been  .suggested 
that  the  infection  is  transi)eritoncal, — that  is,  through  the  peritoneal 
cavitv;  but  if  such  were  the  usual  route,  abscesses  in  other  organs — for 
example,  the  spleen— ought  to  be  more  fre(]uent,  and,  besides,  this  does 


Fic.  364. — MI-LTIPI.E  Amebic  Abscess  of  Liver.    (One-half  natural  size.) 

A.  DiaphraRm.     B.    B.    Points   of   necrosis   in   liver   tissue.     C.    N'ecrotic   wall   of   an   abscess   extending    into 

(liaphraKm.      /'.  Disapr^arinR  septum  between  two  juxtaposed  absccs-scs. 


c 


not  account  for  the  deep  location  of  the  abscess,  and,  in  addition,  trans- 
portation of  the  amebae  by  the  portal  blood  seems  much  more  reasonable. 
The  abscesses  vary  in  size  from  small  cavities  2  cm.  or  3  cm.  in  diameter 
to  large  collections  around  which  the  right  lobe  forms  a  thin  shell  from  a 
few  millimeters  to  a  centimeter  in  thickness.  The  material  contained 
within  the  ab.scess  is  composed  of  necrotic  fragments  of  hepatic  tissue, 


752 


SPECIAL    PATHOLOGY. 


granular  detritus,  amebee,  and  relatively  few  leukocytes.  In  the  smaller 
abscesses  before  liquefaction  is  complete  the  necrotic  material  is  thick  and 
viscid  and  often  will  not  flow  through  a  medium-sized  cannula.  The  wall 
of  the  abscess  is  composed,  on  the  inner  surface,  of  necrotic  liver  cells 
and  shreddy  projections  of  residual  connective  tissue;  masses  of  fibrin 
can  usually  be  recognized.  The  liver  cells  beyond  the  zone  of  actual 
necrosis  are  greatly  flattened  and  distorted,  and  some  are  necrotic; 
within  this  zone  small  areas  of  hemorrhage  can  sometimes  be  seen. 
The  absence  of  polvmorphonuclear  leukocytes,  or,  at  most,  the  small 
numbers  present,  show  that  the  process  is  not  suppurative  in  the  ordin- 
arv  interpretation  of  the  term.  Bacteria  may  be  present,  and  it  is 
quite  possible  for  an  amebic  abscess  to  be  secondarily  infected.     While 


YiQ_  365. — Liver,  Wall  of  an  Amebic  Abscess.     (Fixed  ia  Bensley's  fluid;    paraffin;   eosin  and  toluidin-blue.) 

A,  A.  Abscess  containing  detached  and  fragmented  hepatic  cells  and  cellular  detritus.     B,  B.  Hepatic  tissue  mar- 

ginating  the  atiscess  cavity;   the  inner  margin  of  this  zone  is  composed  of  necrosing  liver  cells;    the  adjacent 

columns  of  cells  are  compressed  and  distorted.     C,  C.  Area  of  periportal  tissue  showing  considerable  edema 

and  necrosis  and  slight  cellular  infiltration.     D.  Bile-duct. 


Other  forms  of  hepatic  abscess  frequently  give  rise  to  embolic  processes 
and  metastatic  foci  in  other  organs,  the  amebic  abscess  rarely  does  so. 
Kartulis^  reports  a  case  of  secondary  brain  abscess  in  which  the  amebae 
were  identified. 

The  course  of  developed  hepatic  abscesses  varies.  Over  fifty  per 
cent,  of  those  that  are  sohtary  rupture  through  the  diaphragm,  and  the 
larger  number  of  these  penetrate  the  lung  and  discharge  into  a  bronchus. 
About  twentv  per  cent,  rupture  into  the  peritoneum.  Few  become  en- 
capsulated and  assume  a  quiescent  stage.  The  remainder  are  evacuated 
through  the  stomach,  intestines,  kidney,  bile-passages,  or  externally; 
Flexner  reported  an  amebic  abscess  that  ruptured  into  the  vena  cava. 
1  "Centralbl.  f.   Bakt.,"   Dec.   12,    1904,  p.   527 


lAvvAi.  753 

Chronic  interstitial  hepatitis,  or  cirrhosis  of  the  liver,  is  a  chronic 
productive  lesion  characterized  l)y  the  formation  of  fibrous  tissue,  which, 
in   some  instances,   contracts.     The  varied   pictures   presented  by  the 
dissimilar  manifestations  of   cirrhosis,  and  ditTerent  conceptions  as  to 
its  origin,  permit  of  extremely  comj)lex  classifications,  many  of  which 
inchule  forms  that  cannot  be  identified  by  clinical  methods  at  present 
at  our  disposal.     It  is  clear  that  the  structural  changes  observed  are 
the  result  of  some  form  of  irritation,  and  that  in  one  class  of  cases  the 
irritant  enters  the  organ  by  the  portal  system  and  that  in  another  gnmp 
the  deleterious  action  is  exerted  by  way  of  the  biliary  passages.     There 
is  no  anatomic  or  clinical  group  of  cases  that  would  justify  a  belief 
that  a  special  form  of  cirrhosis  resulted  from  the  action  of  an  irritant 
brought  to  the  liver  by  the  hepatic  artery;     attempts  to  establish  an 
arteriosclerotic  cirrhosis  of  the  liver  have  not  been  convincing.     There 
remain,  however,  the  two  groups  to  which  I  have  referred  ;    the  first 
mav  be  called  portal  cirrhosis  and  the  second  biliary.     The  former  may 
be  further  subdivided   into — (i)   a  type   characterized  by   contraction 
and  marked  induration,   called  atrophic   cirrhosis,   and   (2)   a  form  in 
which  the  organ  remains  large  and  is  the  seat  of  a  concurrent  intense 
fattv  infiltration — fatty  cirrhosis.      The  biliary  cirrhosis  can  be  further 
divided  into — (a)  a  form  due  to  obstruction  of  the  larger  bile-ducts — 
obstructive    biliary    cirrhosis;    and    (6)    the    hypertrophic    cirrhosis    of 
Hanot.'     In  addition  to  the  lesions  mentioned  there  is  a  chronic  hyper- 
plastic process  affecting  the  hepatic  capsule,  which  becomes  enormously 
thickened,  giving  rise  to  a  condition  called  capsular  cirrhosis. 

Atrophic  cirrhosis-  of  the  liver  is  also  known  as  fibroid  liirr,  ^ra)uilar 
liver,  giii-driiikcrs'  liver,  hob-nail  liver,  eoniraetiiig  or  eontraeted  liver, 
ehrouie  interstitial  eirrliosis,  venous  cirrhosis,  and  LacnJtcc's  cirrhosis. 
According  to  White,  alcohol  is  accredited  with  sixty  per  cent,  of  the 
cases  of  atrophic  cirrhosis;  but  the  experimental  production  of  cirrhosis 
in  animals  by  the  administration  of  alcohol  by  either  the  stomach  or 
portal  vein  has  not  been  conclusive.  It  is  possible  that  the  gastro- 
enteric catarrhal  and  fermentative  conditions  occurring  in  alcoholics 
have  something  to  do  with  the  production  of  cirrhosis.  Syphilis  is  re- 
sponsible for  some  cases;  rickets,  red  atrophy,  malaria,  and  infectious 
diseases  are  also  etiologic  factors  in  the  production  of  the  condition. 
The  increased  fibrous  tissue  observed  in  chronic  congestion,  malaria, 
and  chronic  infections  rarely  attains  the  magnitude  seen  in  typic  atrophic 
cirrhosis.  It  is  probable  that  more  than  one  toxic  condition,  or  at  least 
that  a  number  of  poisons,  may  so  irritate  the  liver  as  to  produce  an 
increased  quantity  of  fibrous  tissue.  There  has  been  much  discussion 
as  to  whether  the  fibrous  hyperplasia  is  primary  or  secondary;  recent 
investigation  indicates  that  the  initial  change  is  a  necrosis  affecting  the 

'  Those  interested  in  a  more  detailed  classification  of  tlie  cirrhosis  should 
consult  Rolleston.  'Diseases  of  the  Liver."  1005.  p.  174.  Edwards.  "International 
Clinics."  vol.  ii,  twelfth  series.  Also  Ascoli,  "Deut.  Arch,  f  klin.  Med."  Rd. 
Ixxi.  H.  4  and  5. 

*  Vauphan.  "jour.  Amer.  Med.  Assoc.,"  Oct.  5.  1901.  W.  Hale  While,  "Brit. 
Med.  Jour.."  March  7.  100,^.  p.  533.  Rleichrodcr.  "\  irchow's  Arch.,"  vol.  clxxvii, 
No.  3.  Klippel  and  Lcfas,  "Rev.  de  Med.."  jan  10.  1Q03.  Joannovics,  "Wien. 
klin.  Woch,"  July  7.  1904.  p.  757.  Kretz,  "Centralbl.  f.  allg.  Path  u.  path. 
Anat.."    Dec      :i      mo  1     n     <.S;. 

49 


754 


SPECIAL   PATHOLOGY. 


periphery  of  the  lobules,  and  that  this  is  followed  by  the  fibrous  over- 
growth (see  Productive  Inflammation,  p.  297). 

Morbid  Anatomy. — In  atrophic  cirrhosis  of  the  liver  the  organ  is 
diminished  in  size,  not  infrequently  weighing  less  than  one  kilo;  the 
surface  is  uneven,  irregular,  granular,  or  hob-nailed;  the  tissue  is  un- 
usually hrm  and  semielastic,  and  offers  considerable  resistance  when 
incised;  it  may  creak  under  the  knife.  In  typic  cases  the  liver  is  pale 
yellow,  but  if  jaundice  has  been  present,  it  may  possess  something  of 
an  orange  tinge  or  be  green  or  greenish-yellow.  An  intercurrent  red 
atrophy  is  sometimes  present,  in  which  case  the  usual  pallor  is  obscured 
by  the  abnormal  amount  of  blood  present.  The  capsule  is  frequently 
thickened  and  occasionally  is  adherent  to  the  diaphragm;  adhesions 
when  present  are  abnormally  vascular  and  rarely  firm.     The  gall-blad- 


FiG.  366. — Superior  Aspect  of  Liver,  Showing  Unusual  Degree  of  Cirrhosis  with  "Hob-n.uled"  Surface- 
A.  Gall-bladder.     The  patient  was  a  chronic  alcoholic  and  died  from   gastro-esophageal    hemorrhage.     (Illus- 
tration one-half  natural  size.) 


der  is  usually  slightly  diminished  in  size,  the  wall,  particularly  in  the 
serous  coat,  is  frequently  thickened.  The  bile  may  appear  normal, 
but  is  frequently  watery  and  dark;  in  other  cases  it  is  thick  and  ropy. 
The  incised  surface  is  traversed  by  grayish,  often  semitranslucent  lines 
or  coarser  bands  composed  of  the  newly  formed  fibrous  tissue.  In  the 
presence  of  intercurrent  red  atrophy,  the  connective  tissue  may  be  red, 
but  is  practicallv  always  lighter  in  color  than  the  hepatic  cells  which 
it  surrounds.  From  the  coarse  bands  finer  projections  can  usually 
be  traced  around  the  lobules. 

The  most  striking  histologic  change  is  the  enormous  increase  in 
fibrous  tissue.  The  distribution  of  this  substance  has  been  used  as  a 
basis  for  certain  anatomic  subdivisions;  when  the  bands  enclose  a 
number  of  contiguous  lobules  the  condition  is  called  polylobular  cir- 


1. 1  \-  K  R . 


/  3.") 


rhosis.  In  the  monolobular  cirrhosis  tlie  tendency  of  the  intercalated 
fibrous  elements  is  to  surround  and  isolate  each  lobule  separately. 
Usually  both  types  can  be  recoj^nizeil.  althoui^h  one  may  predominate. 
The  fact  that  the  til)rous  tissue  is  around  the  lobule  rather  than  in  it 
has  led  to  the  desi<,Miation  perilobular  cirrhosis  or  interlobular  cirrhosis. 
When  the  fibers  extend  between  ihv  coluiiins  of  liver  cells  toriiiiii^'  the 
lobule,  the  condition  is  called  intralobular  cirrhosis  ;  this  form  is  more 
common  in  the  hypertrophic  and  obstruetne  types  of  cirrhosis.  The 
extent  of  the  tibriliation  in  the  newly  formed  tissue  is  largely  determined 


w 


.'•y. 

-  .' ! 

''  'J  .'    ' 

-:l 

■''\^-^\        ,. 

.;•« 

■% 

V>  '''i.J  '  '  "'"~''   '  ■  ■•'' 

Fig.  367. — .\trophic  Cirrhosis  of  the  Liver,  .\dvancxd. — (Schmaus.)     X  so  di.-imctcrs. 
a.  Liver  lobule,    b,  b.  Newly  formed  fibrous  tissue,    c.  Bile-ducts,    d,  e.  f.  Granules  or  hob-noil.s  on  the  surface, 
of  the  liver,  due  to  contraction  of  the  newly  formed  connective  ti>wue.    If  the  masses  arc  small,  they  appear 
on  the  surface  of  the  ornan  as  granules;  if  large,  they  form  hob-nails,     g.  Branch  of  portal  vein.     ».  Hepatic 
vein  in  center  of  lobule. 

by  its  age.  In  the  more  recent  stages  the  interstitial  increase  is  com- 
posed largely  of  mononuclear  cells.  Later  these  can  be  seen  forming 
fibrous  tissue,  and  when  the  lesion  is  advanced,  the  thick  cicatricial 
bands  are  often  nearly  acellular.  As  long  as  the  lesion  is  progressing, 
however,  mononuclear  cells  are  present  in  the  more  recent  areas,  usually 
adjacent  to  the  receding  lobules.  The  studies  of  a  number  of  observers 
show  that  the  new  tissue  often  contains  elastica  in  varying  amounts; 
this  substance,  however,  is  not  invariably  increased,  as  I  have  examined 
a  specimen  of  advanced  cirrhosis  in  which  there  is  no  manifest  produc- 


756  SPECIAL  PATHOLOGY. 

tion  of  elastic  tissue.  Often  columns  of  cuboidal  cells  suggesting  new 
bile-ducts  are  present  in  the  interstitial  tissue.  It  is  possible  that  these 
structures  are  due  to  regenerative  efforts  on  the  part  of  the  liver  cells; 
their  exact  nature,  however,  is  still  a  matter  of  doubt.  In  some  forms 
of  cirrhosis,  yellowish  or  brownish  granules  of  pigment  are  found  in 
the  new  tissue  and  in  the  liver  cells.  In  most  cases  the  granules  are 
derived  from  the  erythrocytes  as  a  result  of  hemolytic  processes.  The 
pigment  in  cirrhosis  anthracotica  is  of  extraneous  origin  (exogenous), 
and  has  reached  the  liver  by  the  blood  (see  p.  232). 

The  portal  vein  and  its  branches  are  dilated,  the  large  vein  of  the 
round  ligament  is  often  conspicuous,  and  sometimes  dilated  veins  are 
seen  beneath  the  skin,  around  the  umbilicus,  constituting  the  so-called 
caput  medusae.  The  gastric  and  esophageal  veins  may  be  varicose, 
and,  by  rupturing,  sometimes  give  rise  to  fatal  hemorrhages.  The  spleen 
is  moderately  enlarged,  the  capsule  frequently  thickened,  and  sometimes 
adherent  to  contiguous  structures;  there  is  some  doubt  as  to  whether 
the  splenic  enlargement  is  due  to  venous  stasis  alone  or  is  the  result 
of  toxemia.  Klippel  and  Lefas  have  recently  studied  the  notable  scle- 
rosis of  the  pancreas  often  associated  with  contracting  liver;  in  some 
cases  the  production  of  fibrous  tissue  in  the  interior  of  the  pancreas 
is  most  marked.  In  the  earlier  stages,  and  later  when  edema  is  present, 
the  organ  may  be  enlarged.  The  intestinal  mucosa  shows  the  results 
of  chronic  congestion,  and  catarrhal  inflammations  of  the  intra- 
abdominal alimentary  canal  are  frequently  present.  Ascites  occurs  in 
fiftv  per  cent,  of  the  cases;  it  is  usually  attributed  to  the  heightened 
venous  tension  resulting  from  portal  obstruction  within  the  liver,  but 
may  also  be  due  to  thrombosis  of  the  portal  trunk  or  of  its  intrahepatic 
branches,  toxemia,  peritoneal  irritation,  and  cardiorenal  changes. 
Jaundice  with  atrophic  cirrhosis  occurs  in  less  than  one-third  of  the 
cases;    it  is  rarely  marked,  and  is  usually  transient. 

Fatty  Cirrhosis. — In  addition  to  the  increase  in  the  connective  tissue 
observed  in  atrophic  cirrhosis,  there  may  be  more  or  less  fatty  infiltra- 
tion, giving  rise  to  an  organ  that  but  little  resembles  the  preceding. 

Morbid  Anatomy. — The  fatty  cirrhotic  liver  is  large  and  is  usually 
smooth,  but  maybe  slightly- granular;  as  a  rule,  the  surface  is  undulat- 
ing and  distinctly  yellow  in  color;  the  organ  possesses  the  rounded 
margin  and  general  rotundity  already  noted  as  present  in  fatty  infiltra- 
tion (see  p.  743;  also  examine  Fig.  362,  p.  744);  on  section,  however, 
it  is  very  much  firmer,  and  contains  an  excess  of  fibrous  tissue  as  well  as 
of  fat ;  the  fibrous  tissue  is  distributed  in  the  same  manner  as  in  atrophic 
cirrhosis,  and  with  the  same  result,  except  that  the  extensive  infiltra- 
tion of  fat  enlarges  the  organ.  The  fibrous  tissue  is  not  so  abun- 
dant and  commonly  is  structurally  immature.  The  venous  obstruction 
is  usually  less,  and  the  alterations  in  other  organs  are  not  so  marked 
as  when  contraction  is  conspicuous.  In  my  experience  this  form  of 
cirrhosis  is  more  likely  to  be  latent,  often  gives  rise  to  no  symptoms, 
and  frequently  reaches  the  autopsy  table  undiagnosed. 

Obstructive  biliary  cirrhosis^  results  from  increased  pressure  within 
the  bile-ducts,  although  it  is  evident  that  some  additional  factor  is  neces- 

^  Ford,  "Amer.  Jour.  Med.  Sci.,"  Jan.,  1901.  Weber,  "Trans.  Path.  See. 
of  London,"  3903,  vol.  liv,  p.  103.  Pick,  "Wien.  klin.  Woch.,"  April  23,  1903, 
P-  493- 


LIVER.  757 

sary,  as  duct  obstruction  may  be  complete  and  long  continued  without 
producin.i?  typic  biliary  cirrhosis.  Retention  of  bile  within  the  liver 
often  gives  rise  to  necrosis  of  the  hepatic  epithelium  and  a  productive 
inflammation  around  the  finer  biliary  channels.  The  causes  of  duct 
obstruction  will  be  considered  with  the  biliary  passages. 

Morbid  A ihitoiu v. —In  the  earlier  stages  the  liver  is  greatly  enlarged, 
but  later  contracts.  During  the  period  of  enlargement  the  organ  re- 
sembles the  liver  of  tyy)ic  hypertrophic  cirrhosis.  Often  the  dilated 
ducts  can  be  seen  through  the  capsule;  adhesions  to  contiguous  struc- 
tures occur.  The  liver  resists  incision,  is  intensely  bile  stained,  the 
surface  uneven  or  granular,  and  rarely  bossed;  in  the  latter  case  it 
resembles  the  hob-nail  liver.  The  incised  surface  discloses  transverse 
and  oblique,  less  frequently  longitudinal,  sections  of  dilated  bile-chan- 
nels, the  walls  of  which  are  manifestly  thickened.  The  distribution 
of  the  fibrous  tissue  is  less  uniform  than  in  atrophic  cirrhosis,  and  its 
cellular  character,  during  the  stage  of  enlargement,  is  like  that  seen  in 
hypertrophic  cirrhosis.  Histologically,  the  new  tissue  is  both  inter- 
lobular and  intralobular;  the  larger  fibrous  masses  follow  the  lines  of 
dilated  ducts,  but  are  also  projected  around  the  walls  of  biliary  canals 
in  which  dilatation  is  inconspicuous.  In  some  cases  focal  necroses  are 
abundant,  and  degeneration  of  the  hepatic  epithelium  is  advanced; 
the  former  condition  is  absent  more  frequently  than  the  latter.  As- 
cites in  obstructive  biliary  cirrhosis  is  rare.  The  fact  that  the  spleen 
is  not  greatlv  enlarged,  and  that  venous  distention  is  inconspicuous 
or  absent,  indicates  that  but  little  vascular  obstruction  is  present.  The 
most  disastrous  termination  of  these  cases  results  from  pyogenic  infec- 
tion of  the  dilated  channels  and  wide-spread  suppurative  cholangitis, 
with  multi])lc  aV)scesses  alon^^  tlie  course  of  the  infected  ducts. 

Hypertrophic  biliary  cirrhosis,'  sometimes  called  biliary  cirrhosis, 
or  simplv  hypertrophic  cirrhosis,  is  characterized  by  marked  enlarge- 
ment of  the  liver  and  spleen,  the  absence  of  ascites,  and  the  presence 
of  an  intense  and  protracted  jaundice;  occlusion  of  the  larger  ducts 
is  absent.  As  the  liver  is  enlarged  in  obstructive  cirrhosis,  fatty  cir- 
rhosis, and  sometimes  in  the  earlier  stages  of  atrophic  cirrhosis,  the  use 
of  the  unqualified  term  hypertrophic  should  be  suppressed,  and  as  the 
obstructive  cirrhosis  is  clearly  of  biliary  origin,  the  use  of  the  term 
biliarv  cirrhosis  without  qualification  gives  rise  to  confusion.  The 
cause  of  the  condition  is  quite  obscure.  It  frequently  occurs  in  the 
young,  and  there  are  recorded  instances  suggestive  of  hereditary  in- 
fluences. The  evidences  of  inflammation  in  the  smaller  biliary  canals 
has  suggested  an  infectious  origin,  although  no  specific  organism  has 
been  isolated.  If  due  to  bacteria,  the  location  of  the  lesion  must  be 
taken  as  an  evidence  of  a  descending  cholangitis. 

Morbid  Aiiatowy. — The  organ  is  large,  much  darker  than  the  pre- 
ceding varieties,  and  of  a  greenish-yellow  color;  the  surface  is  smooth, 
the  margin  rounded,  the  gall-bladder  retracted,  and  the  tissue  is  firm  and 
off'ers  marked  resistance  to  incision.  The  cut  surface  is  usually  pig- 
mented and  liile  stained,  and  the  newly  formed  connective  tissue  can 
be  seen  widely  distributed  among  the  lol^ules. 

There  is  an  abundance  of  mononuclear  or  oval  cells  between  the 

'  The  literature  is  quoted  in  full  by  Rolleston,  "Diseases  of  the  Liver,  Gall- 
bladder, and  Bile-ducts,"  1005. 


758  SPECIAL  PATHOLOGY. 

lobules,  and  even  extending  into  the  tissue  of  the  lobule.  The  bile- 
ducts  appear  to  be  increased  in  size  and  number,  and  the  grouped  ducts 
sometimes  form  adenoma-like  aggregations.  By  reason  of  the  absence 
of  contraction  there  is  little  obstruction  to  the  portal  circulation,  and 
hence  there  is  no  dropsy.  The  increased  interlobular  proliferation  and 
swelling  probably  obstruct  bile-ducts,  and  in  this  way  give  rise  to  the 
jaundice.  The  spleen  is  notably  enlarged,  weighing  between  400  gm. 
and  1000  gm.,  and  in  rare  cases  weighs  more  than  the  liver.  Fibrous 
changes  have  been  observed  in  the  pancreas.  All  the  body  tissues  are 
intensely  bile  stained.  About  ten  years  ago  Gilbert  and  Lereboullet^ 
called  attention  to  clubbing  of  the  fingers  in  hypertrophic  biliary  cir- 
rhosis; it  is  said  that  this  manifestation  occurs  in  no  other  form  of 
hepatitis. 

Pseudocirrhosis,-  also  called  hepatic  capsulitis,  perihepatitis,  and  cap- 
sular cirrhosis,  is  probably  a  form  of  chronic  serous  membrane  inflam- 
mation— a  chronic  hyperplastic  hyaloserositis  (p.  473) — and  should  not 
be  grouped  with  the  cirrhoses.  Local  capsular  thckenings  are  without 
clinical  significance,  and  it  is  only  when  the  liver  is  practically  covered 
by  a  thick  stratum  of  condensed  hyaline  fibrous  tissue,  giving  rise  to 
contraction,  that  the  condition  becomes  important.  Rolleston  differen- 
tiates it  from  perihepatitis  by  the  fact  that  the  new  tissue  is  beneath 
the  capsule;  other  writers  do  not  make  the  distinction.  The  surface 
of  the  organ  is  covered  by  hyaline  fibrous  tissue  ("Zuckergussleber," 
iced  liver)  which  resists  incision;  sometimes  there  is  a  slight  cirrhosis, 
but  never  the  changes  of  the  typic  chronic  interstitial  hepatitis.  Vas- 
cular distention  and  wasting  of  the  epithelium  (red  atrophy)  are  usually 
present.  Pericardial  adhesion  and  thickening  of  the  splenic  capsule 
are  also  observed;    ascites  is  sometimes  marked. 

Syphilis  of  the  liver  ^  may  result  from  either  congenital  or  acquired 
infection.  In  congenital  syphilis  three  important  structural  altera- 
tions are  to  be  recognized:  (i)  extensive  intercalation  of  fibrous  tissue 
between  the  lobules,  but  extending  into  and  around  the  cells  {pericel- 
lular cirrhosis).  This  may  be  diffuse,  involving  all  the  organ,  or  re- 
stricted to  definite  paths  which  possibly  correspond  to  the  distribution 
of  the  vessels.  The  hepatic  cells,  within  the  areas  of  fibrosis,  are  usually 
shrunken  and  often  necrotic.  (2)  Miliary  giimmata,  consisting  of  small 
collections  of  lymphoid  cells  in  which  stellate  or  sharply  defined  giant 
cells  are  occasionally  observed.  In  many  cases  the  diftuse  lesion, 
first  described,  is  concurrent  with  the  development  of  almost  micro- 
scopic granulomata.  (3)  Gummata,  corresponding  to  the  usual  type 
of  syphiloma,  occasionally  occur  in  congenital  syphilis;  they  are,  how- 
ever, infrequent.  By  contraction,  the  diffuse  pericellular  cirrhosis  may 
diminish  the  size  of  the  liver,  or,  what  is  more  common,  the  fibrosis — 
either  pericellular  or  multilobular — follows  irregular  paths  through  the 
organ,  and,  when  it  contracts,  divides  the  liver  into  many  lobes — the 
polylohulated  liver  of  co)igenital  syphilis.  With  regard  to  the  hepatic 
lesions  of  acquired  syphilis,  especially  during  the  secondary  period,  we 

^  See  "Gaz.  Hebd.  de  Med.  et  de  Chir.,"  1902,  Nos.  i  and  2,  p    i. 

^  See  second  foot-note,  p.  472:    also  Schupfer,  "  Rif .  Med.,"  March  2,  IQ04. 

3  Erdmann,  "Deut.  Arch.  f.  klin.  Med.,"  1902,  Bd.  Ixxiv,  H.  5  and  6.  ^Stock- 
ton, "Jour.  Amer.  Med.  Assoc,"  Nov.  8,  1902,  p.  1167.  Boix,  "Arch  Gen.  de 
Med.,"   Paris,    1903,  vol.  Ixxx,  Nos.    19,   20. 


I.IVKU. 


50 


possess  but  little  aerurate  kiiowled.^e.  The  fact  tliat  jaundice  and 
hepatic  enlaru;einent  occur,  and  that  hiter  cirrhosis  may  develop,  indi- 
cates the  possibility  of  an  acute  difYuse  interstitial  hepatitis  and  catar- 
rhal cholani^ntis.  Later  syphilitic  infection  i^ives  rise  to  definite  ^ummata 
(p.  i7q).  These  may  occupy  the  interior  of  the  origan,  ytresent  on  the 
surface  as  delinite  bosses,  or  rarely  as  semi])edunculated  masses.  The 
margin  of  the  gumma  is  not  sharply  defined,  and,  as  Hirch-IIirschfeld 
observes,  the  mass  can  seldom  be  shelled  out  of  the  hepatic  tissue; 
even  in  the  pedunculated  syphilomata  liver  tissue  is  present  in  the 


FiC.    368.— LSDtR    St'RFACK   OF    I-IVKR    Slli>\VlSr.    ResVLTS    OF    CONGENITAL   S\TliaiS. 

.1,  .1.  Gall-bladder.  B.  Round  liRamont.  The  orKan  is  irregularly  fissured  in  many  directions,  riviiik  n>c  to 
a  larRc  numlHT  of  IoIh-s.  I'lie  iKilient  from  whom  this  liver  was  removed  dietl  in  the  second  week  of  typhoid 
fever;    age,  seventeen  years. 


pedicles  and  partly  incloses  the  nodule.  Scars  from  healed  gummata 
may  sometimes  be  observed.  It  is  well  known  that  syphilitics  are  sub- 
ject to  amyloid  disease,  and  that  this  afTection  commonly  involves  the 
liver  (p.  227). 

Tuberculosis  of  the  Liver.' —Pulmonary  tuberculosis  is  often  accom- 
panied by  fatty  infiltration  of  the  liver,  with  which,  or  independently, 
a  ])eriportal  cirrhosis  sometimes  occurs.     It  is  known  that  the  poison 

'  Moussct   and    Bonainour,    "Rev.   de    .MOd.,"   April.   TQ04.      Vincer;"^>     •  Rif 
Med.,"  Nov.  16,  1904.      Giordano,  "Rif.  Med.,"  Nov.  46.  1904. 


76o 


SPECIAL  PATHOLOGY. 


of  the  tubercle  bacillus  sometimes  manifests  a  sclerogenous  quality, 
and  it  is  possible  that  some  of  these  forms  of  cirrhosis  are  due  to  the 
action  of  the  bacillary  toxins  brought  to  the  liver  bv  the  circulating 
blood.  Tuberculosis  of  the  liver  may  be  primary  or  secondary;  the 
former  is  exceedingly  rare.  Infection  may  occur  by  the  portal  blood, 
hepatic  artery,  lymphatics,  or  by  contiguity;  the  hematogenous  routes 
are  the  usual  paths  by  which  the  bacillus  enters  the  organ.  Infection 
of  the  liver  b}^  the  tubercle  bacillus  gives  rise  to  miliary  tubercles,  or 
in  the  more  chronic  form,  cheesy  areas  of  various  sizes,  and,  rarely, 
extensive  caseation  involving  a  large  part  of  the  liver,  constituting  the 
so-called   cold   abscess.     Miliary   tubercles    and   miliary   gummata   are 


U  ■^A. 

/"?>. 


^m 


.^4 


Fig.  369. — Syphilitic  Cirrhosis  of  the  Liver. — {Schmaus.)     X  40  diameters. 
a.  Liver   capsule,     b,  b.  b.  Newly  formed  connective  tissue,  which  is  grouped  in  a  band-like  area    as  at  g.    c. 
Branch  of  portal  vein.     /,  /,  /.  Liver  lobules,     e.  Deep  fissure  produced  in  the  liver  surface  by  the  traction 
exerted  by  the  fibrous  bundles,  g. 


often  quite  similar,  and  a  microscopic  or  bacteriologic  examination  may 
be  necessary  to  differentiate  the  lesions.  Miliary  tuberculosis  of  the 
liver  usually  produces  marked  enlargement  of  the  organ.  It  is  fre- 
quently concurrent  with  peritoneal  tuberculosis,  which  may  be  inter- 
preted as  indicating  that  the  infection  has  arisen  in  the  portal  system 
or  that  the  peritoneal  lesion  is  secondary  to  the  hepatic  manifestation. 
In  acute  cases  the  tubercles  are  small  and  of  the  gray  type  (p.  149) ;  after 
the  lesion  has  persisted  longer  they  become  yellow  and  often  distinctly 
caseous.  Localized  tuberculosis  of  the  liver  is  manifested  by  caseous 
nodules  called  solitary  tubercles.  The  term  solitary  must  be  given  the 
same   liberal  construction  as  when  applied   to  solitary  abscesses;   both 


I.IVKU.  761 

lesions  art'  lrc"<iuciilly  multiple.  The  solitary  tuiiertie  is  a  nrcuin- 
scribed  caseous  area  surrouncled  by  a  capsule  which  may  be  thick  and 
dense  of  exceetlinj^dy  thin.  The  tuberculous  abscess  usually  results 
from  secondary  infection  of  a  solitary  caseous  area.  When  the  cheesy 
noduk's  rujiiurc  into  a  bik'-duct,  caseous  cholanj^itis  commonly  follows. 

Actinomycosis  of  the  liver'  may  be  primary  or  secondary;  of  Ari- 
baud's  seven  cases  of  primary  hepatic  actinomycosis,  Auvray  believes 
that  three  are  genuine.  Of  the  thirty-one  cases  collected  by  Auvray, 
seven , were  due  to  direct  extension  from  the  alimentary  tube;  eleven 
were  infections  by  the  portal  blood.  Propagation  from  the  kidney  or 
lung  is  less  frequent.  Abscesses,  miliary,  multiple  or  single,  always 
develop.  The  liver  becomes  adherent  to  the  abdominal  wall  or  some 
contiguous  viscus,  and  extending  necrosis  gives  rise  to  fistulous  paths 
and  external  openings;  all  the  reported  cases  have  proved  fatal.  The 
diagnosis  is  made  by  demonstrating  (p.  167)  the  fungus  in  the  tissues 
or  discharges. 

Leprosy  of  the  liver  is  a  rare  manifestation  of  the  tubercular  or  nodu- 
lar form  of  the  disease,  The  histology  of  the  leprous  nodule  is  described 
on  p.  1 50. 

Tumors  of  the  Liver. — Adenoma  may  arise  from  the  liver  cells 
or  from  the  epithelium  of  the  intrahepatic  ducts.  Birch-Hirschfeld 
observed  adenoma  of  the  liver  twice  in  400  autopsies  on  infants. 
Hvpernephroma  (see  p.  662)  of  the  liver  has  been  described.  The  most 
important  of  the  hepatic  tumors  are  the  carcinomata,  w^hich  may  be 
]mmarv  or  secondary*.  Hale  White,  in  10,000  postmortems,  found  ten 
undoubted  instances  of  primary  cancer  of  the  liver;-  the  secondary 
cancers  were  twenty-four  times  as  frequent.  Eggel  collected  163 
instances  of  primary  hepatic  cancer.  It  has  been  observed  in  children, 
but  is  rare  before  middle  life.  Primary  cancer  may  arise  from  the 
hepatic  cells  or  from  the  epithelium  of  the  biliary  ducts;  it  may  be  of  the 
cvlindric-cell  type  or  resemble  the  glandular  cancers.  Xodular.  massive 
or  solid,  and  diffuse  forms  are  recognized.  The  tirst  of  these  consists  of 
bossed,  irregular  nodes,  usually  grouped  in  one  area  of  the  liver,  com- 
monlv  the  right  lobe.  Massive  or  solid  tumors  consist  of  a  single  growth. 
Less  than  one-fourth  of  the  primary  cancers  are  of  this  form.  The  dif- 
fuse form  is  the  rarest  of  hepatic  cancers;  it  gradually  infiltrates  a  lobe, 
and  on  account  of  the  large  amount  of  connective  tissue,  contracts  about 
as  rapidlv  as  it  destroys  the  hepatic  structure,  thereby  preventing  any 
considerable  increase  in  the  size  of  the  organ.  The  usual  form  of  hepatic 
cancer  is  secondary  to  carcinoma  in  some  part  of  the  intra-abdominal 
alimentarv  canal.  Some  of  these  tumors  attain  enormous  dimensions; 
in  the  case  reported  by  Chri.stian  the  liver  weighed  15,110  gm.  The 
secondarv  growths  are  practically  always  multiple,  and  usually  are  dis- 
tributed in  the  liver  from  a  portal  vein.  The  multicentric  character  of 
the  growth  leads  to  the  production  of  a  large  number  of  nodes,  many  of 
which  are  near  the  surface,  upon  which  they  may  be  recognized  as  slightly 
elevated  bosses;   as  a  result  of  degenerative  and  necrotic  changes  in  the 


Auvray.    "Rev.  de  Chir_. "  July,  iqo.^,  p.  i. 

thi 
"A 
1903,  p.  991. 


'  Auvrav.    "Rev.  de  Chir..      jiilv.  1903,  p.  i. 

'Christian.  "Med.  and  Sur^.  Reports  of  the  Boston  City  Hospital."  1902. 
hirteenth  series,  p.  166.  Scheel  "Nord.  Med.  Arkiv.."  Feb.  11.  1902.  Wells. 
Amer.    lour.   Med.  Sci.."  Sept..  190^  p.   403       Burt.   "  Post-nn.du.it.-. "   Nov.. 


762 


SPECIAL  PATHOLOGY. 


interior  and  consequent  contraction  the  center  of  the  boss  is  depressed 
(umbihcated). 

Connective-tissue  tumors  of  the  Hver  are  rare — angiomata  are  prob- 
ably the  most  frequent,  and  are  practically  always  of  the  cavernous 
type;  thev  are  rarely  large,  although  Mantle  reported  an  instance  in 
which  the  tumor  was  20  cm.  by  30  cm.  Angioma  of  the  liver ^  is  con- 
genital, although  other  views  as  to  its  origin  have  been  expressed. 
Myxomata  and  fibromata  are  rarely  found  in  the  liver.  Primary  sar- 
coma of  the  liver  is  even  less  frequent  than  primary  cancer.  It  may 
consist  of  a  single  large  mass,  or  from  such  a  primary  growth  there  may 
be  multiple  nodules  disseminated  through  the  organ.  Histologically 
any  type  of  cell  may  be  present.  Melanotic  tumors  of  the  liver  are 
probably  always  secondary. 


Fig.  370. — Part  of  Left  Lobe  of  the  Liver,  SHO\nxG  Primary  Cylindric-cell  Carctnoma. 
The  slight  umbilication  of  the  cancerous  nodules  is  indicated.     Figure  1 74.  page  328,  is  from  a  section  of  this  tumor. 
(Removed  by  Professor  Keen  from  a  man  fifty  years  of   age.     The  illustration  is  three-fourths  natural  size. 
Mass  weighed  525  gm.     The  patient  recovered.) 


Cysts  of  the  Liver. — Some  of  the  adenomata  of  the  liver  are  cystic, 
and  Boye-  believes  that  the  so-called  cystic  disease  of  the  liver  is  really 
a  form"  of  cystadenoma.  Cysts  resulting  from  occlusion  of  the  bile- 
ducts  were  considered  when  speaking  of  obstructive  biliary  cirrhosis 
(p.  756).  Some,  if  not  all,  of  the  so-called  simple  cysts  arise  in  this 
way.     Those  possessing  a  cihated  epithelial  lining  demand  some  other 


^Schmieden,  "Virchow's  Arch.,"  1900, 
Beitr.,"  1903,  Bd.  xxxiv,  p.  215.  Mantle, 
p.    365. 

^"Centralbl.  f.  inn.  Med.,"  July  ig,  1902 


Bd.  clxi,  p.  373.     Ahaan,  "Ziegler's 
"Brit.  Med.  Jour.,"   Feb.    14,   1903, 


I.INI.K.  763 

exi)lanation.  A  form  of  conLjcnital  cystic  disease  of  the  liver  rcseni- 
blini,'  that  occurriiii,'  in  the  kidney  (p.  665)  is  occasionally  observed. 
They  are  usually  nniltii)le,  but  a  sini^dc  lari,'e  cyst  is  sometimes  present. 
It  is  probable  that  they  arise  from  devch^pmental  errors  in  the  evolu- 
tion of  the  bile-ducts.  The  most  frequent  cyst  of  the  liver  is  the  hy- 
datid (p.  199),  fifty  per  cent,  of  which  are  situated  in  the  organ  under 
consideration.  Xeisser,  in  986  cases  of  hydatid  disease,  found  the  liver 
affected  in  451.  It  is  usually  stated  that  hydatid  cysts  do  not  develop 
in  the  bile-ducts,  but  D6v6  reports  a  case  in  which  the  cavities  were 
lined  by  biliary  epithelium.  Figure  no,  i)age  199,  is  a  hvdatid  cyst 
of  the  liver;  these  cysts  occasionally  inspissate  and  may  become  caseous 
or  cretaceous. 


BILl.ARY  PASSAGES. 

Malformations.' — Occasionally  the  common  duct,  the  duct  of  the 
gall-bladder,  or  the  gall-bladder  itself  may  be  absent;  in  certain  cases 
of  jaundice  in  the  new-born  the  ducts  are  either  absent  or  not  patulous. 

Cholangitis,  or  inflammation  of  the  biliary  ducts,  may  be  a  catarrhal 
process,  cither  acute  or  chronic,  or  it  ma\'  be  siippitrattvc,  and,  in  rare 
instances,  i:,iiiii:,rc>ituts. 

Acute  catarrhal  cholangitis  is  commonly  secondary  to  duodenitis, 
but  may  also  result  from  the  presence  of  gall-stones  or  from  hydatids, 
either  in  the  liver  or  along  the  course  of  the  biliary  passages.  The 
condition  constitutes  the  anatomic  basis  of  the  so-called  catarrhal 
jaundice,  and  is  probably  always  of  bacterial  origin.  It  is  generally 
maintained  that  infection  is  either  ascending  or  descending;  in  the  former 
the  bacteria  enter  from  the  duodenum,  and  in  the  descending  infections 
microorganisms  are  brought  to  the  liver  by  the  blood  and  e.xcreted 
with  the  bile.  The  studies  of  Carmichael-  indicate  that  the  infection 
is  practically  always  of  the  ascending  type.  Embolic  abscesses  within 
the  liver  and  suppurating  hydatid  cysts  may  infect  the  bile-passages. 
Biliary  ducts  are  frecjuently  infected  in  typhoid  and  occasionally  in 
pneumonia  and  other  acute  infectious  diseases.  Any  obstructive  lesion 
which  impedes  the  flow  of  the  bile  favors  infection  and  frequently  gives 
rise  to  cholangitis.  The  inflammation  of  the  ducts  associated  with 
cancer  and  other  tumors  involving  the  lower  part  of  the  biliarv  passages 
is  primarily  the  result  of  obstruction  and  consequent  infection.  The 
changes  in  the  mucosa  are  those  seen  in  catarrhal  inflammations  of  the 
mucous  membranes.  (See  p.  546.)  In  the  milder  forms  of  the  disease 
the  patients  rarely  die,  and  therefore  but  little  knowledge  is  available 
as  to  the  changes  occurring  in  the  liver.  When,  however,  the  condi- 
tion has  persisted  for  any  length  of  time,  the  liver  is  usually  enlarged 
and  the  connective  tissue  surrounding  the  biliary  [)assages  shows  more 
or  less  cellular  infiltration.     The  lobules  may  contain  areas  of  necrosis. 

Chronic  catarrhal  cholangitis,  or  chronic  catarrhal  infianDtiaiioii  of 
the  bilc-diicts,  arises  as  a  result  of  the  continued  action  of  the  causes 
already  given  when  considering  the  acute  form.  The  disease  usually 
invades  the  gall-bladder;  it  may  give  rise  to  obstruction  of  the  cystic 
duct,  and  thereby  induce  considerable  dilatation. 

'  See   Malformations  of  the   Liver,   p.    739. 

'  "Jour,  of  Path,  and  Bact.,"  Sept.,  1902,  j),  276.     Bibliography. 


764  SPECIAL  PATHOLOGY. 

Suppurative  cholangitis,  also  called  phlegmonous  cholangitis,  is  due 

to  pvogenic  infection  of  the  biliary  passages.  The  morbid  process 
usuailv  begins  as,  or  is  associated  with,  a  catarrhal  inflammation, 
and  hence  the  causes  already  given  for  this  process  are  to  a  certain 
extent  influential  in  the  production  of  the  suppurative  lesion.  The 
disease  may  be  secondary  to  cholelithiasis;  it  is  not  infrequently 
associated  with  general  infections,  such  as  occur  in  pyemia,  pneu- 
monia, typhoid  fever,  and  influenza.  The  colon  bacillus,  the  ty- 
phoid bacillus,  and  the  usual  pyogenic  organisms  are  the  bacteria 
most  frequently  present.  As  to  the  course  of  infection,  it  is  probable 
that  in  most  instances  the  bacteria  reach  the  biliary  passages  from  the 
intestinal  canal  by  a  process  of  direct  invasion.  It  is  not  improbable 
that  the  infection  may  occur  through  bacteria  carried  to  the  hepatic 
tissues  by  way  of  the  circulation,  which,  finding  in  the  biliary  passages 
conditions  suitable  for  their  growth,  lodge  and  give  rise  to  inflam- 
mation. Phlegmonous  cholangitis  may  arise  from,  or  terminate  in, 
pyemia  or  septicemia.  The  suppurative  process  may  be  restricted  to 
the  gall-bladder  (phlegmonous  cholecystitis),  in  which  condition  the 
wall  of  the  gall-bladder  becomes  edematous  and  infiltrated  with  leuko- 
cvtes,  which  may  accumulate  in  the  interior  in  sufficient  numbers  to 
justify  the  conclusion  that  the  contents  of  the  gall-bladder  is  pus,  con- 
stituting what  is  called  empyema  of  the  gall-bladder.  Peritonitis  may 
occur  without  perforation  of  the  cystic  wall,  infection  having  traveled 
through  the  lymph-spaces.  The  gall-bladder  is  commonly  greatly 
enlarged,  and  evidence  of  the  septic  character  of  the  inflammation 
is  further  indicated  by  the  systemic  phenomena  attributed  to  the  ab- 
sorption of  toxic  bodies  from  the  area  of  infection.  AVhether  the  pro- 
cess began  in  the  gall-bladder  or  originated  in  the  common  duct  or  its 
ramifications  in  the  liver  can  not  always  be  determined.  When  the 
biliary  system  is  involved  in  a  diffuse  suppurative  cholangitis,  the  liver 
is  usually  enlarged,  and  on  section  pus  may  be  identified  in  and  around 
the  biliary  passages,  which  not  uncommonly  show  more  or  less  dila- 
tation. If  the  disease  be  permitted  to  progress,  and  if  the  patient  sur- 
vive, abscesses,  macroscopically  recognizable,  may  be  found  in  the 
hepatic  tissue.     (See  Hepatic  Abscess,  p.   749-) 

Pseudomembranous  or  fibrinous  cholecystitis  is  exceedingly  rare; 
Rolleston^  has  reported  a  case. 

Tuberculosis  of  the  gall-bladder-  or  tuberculous  cholecystitis  is  infre- 
quent; it  may  involve  the  mucosa  or  interstitial  tissue.  It  is  usually 
secondary. 

Pericholecystitis,  or  inflammation  around  the  gall-bladder,  may  be 
of  any  type  of  serous  membrane  inflammation.  Similar  inflammatory 
conditions  surrounding  the  biliary  ducts  are  called  pericholangitis ; 
both  are  usually  due  to  extension  of  inflammatory  processes  from  the 
interior.  In  the  chronic  productive  or  fibrous  form  of  pericholecys- 
titis the  gall-bladder  is  surrounded  by  masses  of  fibrous  tissue,  the 
wall  greatly  thickened,  and  the  organ  frequently  adherent  to  contig- 
uous structures.  An  interstitial  cholecystitis  has  been  described;  it 
may  be  productive  and  associated  with  great  thickening  of  the  gall- 

'  "Trans.  Path.  Soc.  of  London,"  1902,  vol.  liii,  p.  405. 

^Beitzke,  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.,"  Feb.   15,   1905. 


LIVEK. 


765 


bladder  wall,  or  sui)])urative.  in  which  case  infection  of  the  overlyinj^ 
peritoneum    practically   always  occurs. 

Obstruction  of  the  biliary  ducts,  includinij  the  cystic  duct,  maybe 
due  to  swelling  of  the  mucosa,  gall-stones,  parasites,  such  as  ascarides 
and  flukes,  and  hydatid  cysts;  tumors  within  the  ducts,  neoplasms 
involving  the  contiguous  glands,  duodenum,  or  pancreas;  adhesions 
and  fibrous  bands  around  the  ducts,  prolapsed  kidney,  hepatoptosis, 
and  pseudomembrane  within  the  i)assages  may  produce  occlusion.  A 
similar  condition  results  from  congenital  atresia  or  absence  of  one  or 
more  of  the  ducts.  Obstruction  is  commonly  attended  bv  dilatation 
of  the  passages  above  the  lesion,  and  predisposes  to  infection  and  the 
various  types  of  inflammation  already  described.  Hydrops  cystidis 
felleae  results  from  occlusion  of  the  cystic  duct;  the  gall-bladder  is 
greatly  dilated,  and  most  of  the  biliary  constituents,  except  cholesterin, 
are  absorbed,  leaving  a  colorless,  viscid  fluid  resembling  mucus;  in  some 
cases  the  contained  liquid  is  thin  and  watery.  Unless  the  condition 
has  been  preceded  by  inflammatory  thickening,  the  w^all  of  the  gall- 
bladder is  usually  thin. 

Cholelithiasis  •  includes  the  conditions  which  give  rise  to  gall-stones 
and  the  changes  that  result  from  their  presence  m  the  biliary  passages 
and  gall-bladder.  Biliary  concretions,  or  gall-stones,  usuallv  consist 
of  coloring-matter  combined  with  calcium  and  its  salts,  particularly 
the  carbonate  and  phosphate.  Varying  quantities  of  cholesterin  are 
also  present;  in  the  transparent,  almost  colorless,  or  slightl}'  yellow 
stones  the  largest  percentage  is  found.  Possibly  other  causes  are  not 
without  influence,  but  the  most  important  etiologic  factor  in  the  pro- 
duction of  gall-stones  is  infection.  Of  128  cases  examined  by  Merck, 
in  fifty-three  per  cent,  the  colon  bacillus  was  present,  either  alone  or 
with  staphylococci  or  streptococci;  the  typhoid  bacillus  is  often  found, 
and  may  be  demonstrable  years  after  the  primary  infection.  A  num- 
ber of  observers  have  produced  gall-stones  by  inoculating  the  gall- 
bladder. The  frequency  of  cholelithiasis  in  different  countries  varies. 
In  Strasburg  25.2  per  cent,  of  all  cadavers  of  persons  over  sixtv  vears 
of  age  contain  gall-stones;  Bevan  found  that  sixteen  per  cent,  of 
the  bodies  in  the  Rush  dissecting-rooms  were  affected.  The  size  of 
the  calculi  varies  from  the  so-called  biliary  sand  to  masses  12  cm. 
long  and  5  cm.  thick;  as  a  rule,  the  larger  the  number,  the  smaller 
the  size.  Over  5000  have  been  observed  in  a  single  case.  Their 
most  common  location  is  in  the  gall-bladder;  they  occur  in  the  ducts 
in  the  following  order  of  frequency:  cystic  duct;  cystic  and  common 
ducts;  common  duct;  cystic,  common,  and  hepatic  ducts;  intrahe- 
patic ducts.  Beer  doubts  whether  there  are  over  150  cases  of  intra- 
hepatic cholelithiasis  on  record.  Stones  are  often  latent,  and  some- 
times encysted  or  contained  in  pockets.  Their  dangers  lie  largely  in 
the  complications  to  which  they  give  rise,  the  latter  including  all  forms 
of  inflammation  of  the  gall-bladder  and  ducts,  perforations,  obstruction, 

'  The  literature  of  this  condition  is  extensive.  The  reader  may  consult  the 
following  articles,  which  will  place  him  in  touch  with  the  earlier  communications: 
Mayo.  "Med.  Record."  Feb  21,  ipc.^,  p.  289.  Ewald.  "Amer.  Med.."  July  18. 
1903,  p.  95.  Herter,  "Med.  Xews."  Sept.  26.  1903,  p.  586.  Beer.  "Med.  News." 
July  30,  1904. p.  202.  Bierring.  "Jour.  Amer.  Med.  Assoc., "Oct.  15,  1904, p.  1099. 
Decker.  "Munch,  med.  Woch.."  li.  Xo.  39. 


766  SPECIAL  PATHOLOGY. 

and  secondary  degenerations  and  inflammations,  within  the  Hver,  and 
intestinal  obstruction.  As  a  result  of  adhesions,  the  stone  may  be  dis- 
charged by  perforation  into  the  stomach,  colon,  intestine,  the  pelvis 
of  the  kidney,  or  externally;  in  rare  cases  the  diaphragm  and  the  lung 
are  penetrated. 

Tumors  of  the  Gall-bladder. — Villous  papilloma  of  the  gall-bladder 
occasionally  occurs;  it  often  terminates  in  cancer.  The  most  frequent 
tumor  of  the  gall-bladder  is  cancer;  it  is  commonly  secondary  to  gall- 
stones. The  tumor  is  usually  the  cylindric-cell  type  of  carcinoma. 
Primary  connective-tissue  tumors  of  the  gall-bladder  are  exceedingly 
rare;    fibroma,  lipoma,  and  sarcoma  have  been  observed. 

Tumors  of  the  Bile-ducts. — Papillomata  and  cystadenomata  occasion- 
ally occur;  they  are  most  frequent  in  the  vicinity  of  the  ampulla. 
Primary  cancer  of  the  bile-ducts^  is  also  most  common  in  the  same  area. 
It  also  occurs  at  the  junction  of  the  common  and  C3^stic  ducts,  and  is 
less  frequent  in  the  hepatic  duct;  it  is  usually  the  cylindric-cell  type 
of  cancer.  In  some  cases  the  growth  is  primary  in  the  ampulla  of  Vater. 
Secondary  carcinoma  of  the  bile-ducts  is  usually  due  to  direct  exten- 
sion from  duodenal,  pancreatic,  or  gastric  cancer,  cancer  of  the  liver, 
and  secondary  nodules  in  contiguous  lymph-nodes ;  in  rare  cases  cancer 
of  the  gall-bladder  extends  into  the  bile-ducts. 

'  Maj-o,  "Northwest.  Medicine,"  iVpril,  1903,  p.  173. 


ciiapti:k  XI 1. 

PANCREAS.' 

Normal  Structure.  -Histologically,  this  organ  is  a  reproduction  of 
the  salivary  glands,  consisting  of  acini,  with  smaller  ducts  emj^tying 
into  a  larger  duct  (Wirsung's  duct),  the  latter  terminating  in  the  duo- 
denum incommon  with  the  hepatic  duct.  Recent  investigations  have 
shown  that  probably  the  most  important  structures  in  the  histology 
of  the  organ  are  the  islands  of  Langerhans,  to  the  activity  of  which  is 
gcnerallv  attributed  the  production  of  an  internal  secretion.  The 
islands  are  round  or  oval,  and  consist  of  convoluted  blood-vessels  and 
epithelial  cells.  They  are  equally  abundant  in  the  head  and  body  of 
the  organ,  but  are  much  more  numerous  in  the  splenic  end. 

Malformations-  and  malpositions  of  the  pancreas  are  infrequent. 
There  are  nearly  forty  recorded  instances  of  accessory  pancreas;  such 
bodies  are  found  in  the  wall  of  the  stomach,  duodenum,  jejunum,  or 
ileum,  usually  in  the  submucosa  or  extending  through  the  muscular 
layer  of  the  intestine.  They  consist  of  small  nodules,  rarely  more  than 
2  cm.  or  3  cm.  in  diameter;  they  may  give  rise  to  diverticula  in  the  in- 
testinal or  gastric  wall.  The  duct  of  Santorini  may  be  absent  or  in 
rare  cases  is  larger  than  the  duct  of  Wirsung;  accessory  ducts  are 
rarely  encountered.  Occasionally  the  normal  ducts  enter  the  intestine 
at  unusual  points.  In  the  pancreas  divisum  the  splenic  end  of  the 
organ  is  joined  to  the  head  by  a  i.cdicle  of  fibrous  tissue  containing  a 
duct  and  vessels.  The  annular  pancreas  more  or  less  fully  surrounds 
the  duodenum.  A  bifid  or  lobulated  j^ancreas  is  occasionally  encoun- 
tered. The  tail  of  the  pancreas  may  be  pulled  out  of  position  by  a 
misplaced  spleen,  to  which  reference  has  already  been  made.  (See  p. 
43 r.)  In  Glenard's  disea.se  (visceroptosis  or  enteroptosis)  there  may  be 
a  slight  downward  displacement  of  the  organ,  but  it  is  not,  however, 
marked.  Tumors  and  cysts  occupying  the  retro] )eritoneal  tissues  may 
push  the  pancreas  forward.  Cancers  involving  the  posterior  surface  of 
the  head  of  tlie  organ  may  render  it  distinctly  palpable. 

Postmortem  changes  in  the  pancreas  sometimes  give  rise  to  conditions 
that  are  easily  misinterpreted.  Chiari  has  suggested  that  the  process 
may  begin  during  the  agonal  period.  The  alterations  may  be  uni- 
form throughout  the  organ  or  restricted  to  smaller  areas;  the  presence 
of  altered  blood  may  be  taken  as  an  evidence  of  antemortem  origin. 

•  The  literature  on  diseases  of  the  pancreas  is  quite  extensive;  the  following 
recent  additions  to  our  knowledge  contain  references  to  the  most  important  ar- 
ticles: Opie.  "Disease  of  the  Pancreas.  Its  Cause  and  .Nature."  1903.  Robson. 
"Lancet,  1004,  vol.  i.  Trevor.  "  Practitioner." '  April.  1004.  P-  570-  Hewlett. 
"Jour,  of  Med.  Research."  .Mav.  1004.  p.  .^77.  Sauerbeck.  Ssobolew.  Gutmann, 
.\dler.  "Virchow's  Arch."  1904.  Bd.  clxxvii.  Supp.  Heft.  KarakaschcO.  "Deut. 
Arch.  f.  klin.  Med.."  1904.  Ixxxii.  pp.  Ao-89.  also  "Centralbl.  £.  all^'.  Path.."  Dec. 
^i,  1004.  p.  992.     Hemmeter.  "Amcr.  Med.."  March  ii.  iqo$.  p.  393- 

'  Ruediger.  "Tour.  Amer.  Med.  Assoc,"  .\pril  18.  1903;  bibliogrraphy. 

767 


768  SPECIAL  PATHOLOGY. 

The  affected  structures  are  soft,  cloudy,  and  sometimes  appear  to  con- 
tain more  fluid  than  contiguous  uninvolved  areas.  When  gastric  ulcer 
or  cancer  penetrates  the  pancreas,  postmortem  digestion  is  often  ex- 
treme. Gas  cysts  in  the  pancreas  due  to  the  Bacillus  aerogenes  capsula- 
tus  or  other  gas-producing  organisms  are  occasionally  observed. 

Hyperemia  of  the  pancreas  is  normal  during  digestion  and  occurs 
in  the  initial  stage  of  the  acute  inflammatory  processes  that  affect  the 
organ. 

Congestion  of  the  pancreas  may  be  a  part  of  a  general  abdominal 
congestion,  and  is  most  marked  in  the  presence  of  a  long-continued 
obstructive  lesion  within  the  heart,  or  may  result  from  cirrhosis  of  the 
liver. 

Hemorrhage   into   the  pancreas    {pancreatic  apoplexy  or  pancreatic 
hemorrhage)  is  a  recognized  morbid  process,  although  there  is  consid- 
erable doubt  as  to  its  occurrence  independent  of  inflammation.     Little 
is  known  of  the  cause  of  the  condition;    it  may  occur  at  any  age,  but 
is  most  frequent  in  middle  life  and  later.     It  is  occasionally  associated 
wnth  evidence  of  congestion,  to  which  it  has  been  attributed.     Bunge 
has  suggested  that  it  may  be  of  embolic  origin,  and  others  have  thought 
that  arteriosclerosis  is  a  cause.     It  is  alleged  that  the  continued  use 
of   alcohol   favors  its   occurrence.     It   is   probable,   however,   that  the 
alcohol  is  only  indirectly  responsible  for  the  process,  causing  a  catarrhal 
duodenitis,  which,  in  turn,  is  followed  by  pancreatic  apoplexy.     In- 
herited syphilis  and  infectious  processes  in  the  new-born  are  not  infre- 
quentlv    associated   with   pancreatic    hemorrhage.     Exactly   what   the 
connection  is  can  not,  however,  at  present  be  definitely  stated.     The 
most   important    cause   is   cholelithiasis,    especially   when   a   gall-stone 
occludes  the   opening  of  the   ampulla  into   the  intestine   and  permits 
retrojection  of  bile  into  the  duct  of  Wirsung.     Crushes  and  blows  on 
the  abdomen  may  give  rise  to  hemorrhage  in  and  around  the  pancreas. 
Morbid  Anatomy. — The   hemorrhage   may   be   slight,    consisting   of 
punctate  extravasations  scattered  through  the  organ;     the  extravasa- 
tions may  be  restricted  to  the  interstitial  tissue,  or  the  blood  may  enter 
the  gland  acini.       In  other  cases  the  hemorrhagic   infiltration  is  uni- 
form throughout  a  part  of    the  gland,   commonly  the    head;    and  in 
still   other  instances   the  whole  gland  is    aft"ected.      Occasionally,   the 
hemorrhage  involves  the  tissues   around  the  organ,   extending  to  the 
mesentery  and  retroperitoneal  wall.     The  density  of  the  organ  is  partly 
dependent  upon  the  age  of  the  hemorrhage,  its  extent,  and  the  condi- 
tion of  the  tissues  before  the  hemorrhage  took  place.     The  suffused 
tissues  are  sometimes  soft,  as  a  result  of  liquef active  changes,  or  dense 
in  consequence  of  coagulation.     The  hemorrhages  may  have  occurred 
at  different  times,  as  shown  by  the  fact  that  in  some  areas  old  pigment 
is  found  adjacent  to,  or  in  the  vicinity  of,  manifestly  recent  extravasa- 
tions.    The  source  of  the  hemorrhage  can  seldom  be  located.     Even 
in  the  mild  cases  without  extensive  infiltration  of  the  organ,  recovery 
unassociated  with  inflammation  rarely  if  ever  occurs.     In  the  majority 
of  cases,  however,  the  lesion  terminates  in  an  acute  inflammatory  pro- 
cess.    (See  Acute  Hemorrhagic  Pancreatitis,  below.) 

Fatty  infiltration  of  the  pancreas  is  uncommon;  it  is  sometimes  a 
part  of  general  obesity,  results  from  retardation  of  the  intra-abdominal 
circulation,  or  is  secondary  to  atrophic  degenerative  and  fibroid  processes 


PANCREAS.  769 

occurring  in  the  organ.  Lalmrcoits  infiltration  may  accompany  fat  de- 
posits or  may  follow  hemorrhage  or  inriammation  of  tlic  organ.  The 
calcific  material  is  occasionally  ditluse  and  scanty  in  amount,  or  it  may 
be  collected  in  masses  in  some  part  of  the  organ.  It  is  often  dillicult 
to  decide  whether  the  cretaceous  matter  lies  within  the  ducts  and  is  a 
manifestation  of  pancreatic  lithiasis  or  has  resulted  from  calcific  changes 
in  the  necrotic  areas. 

Cloudy  swelling,  according  to  Ghedini,'  occurs  ])articularly  in  the 
acute  infectious  diseases,  pyemia,  and  septicemia.  I  have  seen  it  in 
typhoid,  {)neunionia,  and  erysipelas,  and  the  condition  is  esj)ecially 
marked  in  protracted  infections  with  high  temperatures.  Ghedini  has 
observed  fatty  degeneration  of  the  pancreas  in  chronic  tuberculosis, 
cirrhosis  of  the  liver,  and  in  cardiac  and  pulmonary  affections  charac- 
terized by  venous  stasis.  Opie  and  others  have  described  hyaline 
transformation  of  the  bodies  of  Langerhans;  this  change  is  most  frc- 
cjuent  in  chronic  inflammatory  conditions  in  which  the  new  connective 
tissue  penetrates  the  lobules. 

Atrophy  of  the  pancreas,  in  the  large  majority  of  cases,  is  secondary 
to  fibrosis  involving  the  connective  tissue  of  the  organ,  and  constituting 
what  is  commonly  described  as  chronic  pancreatitis,  which  will  be  dis- 
cussed with  inflammations  of  the  pancreas.  After  middle  life  the  pan- 
creas not  infrequently  participates  in  the  atropliie  changes  involving 
many  of  the  glandular  viscera,  muscles,  and  other  organs. 

Pancreatitis  {inflammation  of  the  pancreas)  may  be  acute  or  chronic. 
The  acute  fomi  is  usually  subdivided  into  the  acute  hemorrhagic  and 
acute  snfpiiratii'c:  a  i^ant^rciions  type  is  also  recognized. 

Acute  hemorrhagic  pancreatitis  results  from  the  same  causes  as  pan- 
creatic apoplexy  referred  to  above.  Germain  and  Christian-  have  re- 
ported a  case  in  which  inflammatory  phenomena  without  hemorrhage 
were  present.  Opie  believes  that  pancreatic  hemorrhage  and  hemor- 
rhagic pancreatitis  can  not  be  separated.  All  are  agreed  that  acute 
pancreatitis  is  essentially  hemorrhagic.  Many  are  convinced  that  the 
hemorrhage  never  arises  independently  of  inflammation,  and  if  the  em- 
bolic and  traumatic  cases,  and  occasional  instances  of  arteriosclerotic 
hemorrhage,  are  excluded,  I  am  willing  to  subscribe  to  the  prevailing 
opinion.  Macroscopically,  acute  hemorrhagic  pancreatitis,  prior  to  the 
occurrence  of  hemorrhage,  possesses  no  distinctive  character  by  which  it 
can  be  differentiated  from  digestive  changes  occurring  in  the  organ.  In 
the  case  studied  by  Germain  and  Christian  the  pancreas  appeared  normal. 
Hemorrhage  rapidly  ensues,  and  the  picture  is  then  identical  with  that 
of  pancreatic  apoplexy  described  above.  In  addition  to  the  enlarge- 
ment of  the  pancreas  and  the  diffuse  or  circumscribed  infiltration  by 
blood  there  occur  in  the  organ,  in  the  peripancreatic  fat,  and  in  the  fat 
of  the  mesentery,  omentum,  and  abdominal  wall,  areas  of  fat-necrosis 
such  as  are  described  on  page  253.  The  extent  and  size  of  the  necrotic 
lesions  vary;  in  the  mild  cases  there  are  but  few  points  of  necrosis,  in 
other  instances  large  areas  are  involved.  The  serum  of  the  general  peri- 
toneum is  usually  blood-tinged,  and  in  the  cavity  of  the  lesser  omentum 
the  blood  staining  is  usually  marked.  If  the  patient  survive,  the  area 
of  necrosis  be  small,  and  the  escape  of  pancreatic  secretion  be  arrested, 

'  "  Rif .  Med,"  Aup.  2.^,  1904. 

'   "Jour.  Amer.  Med.  Assoc,"  Sept.  24,  1904,  p.  888. 


77° 


SPECIAL  PATHOLOGY 


ultimate  recovery  sometimes  occurs.  In  more  marked  cases,  when  the 
patient  Uves  long  enough,  the  pancreas  softens,  and  becomes  dark  red, 
purphsh,  and  eventually  slate  colored  or  black.  In  the  later  stage 
infection  is  almost  invariably  present,  inducing  a  fetid  odor;  the  pan- 
creas has  become  gangrenous,  and  the  lesion  is  now  called  gangrenous 
pancreatitis.  The  extent  of  the  pancreatic  and  contiguous  necrosis  is 
determined  by  the  size  of  the  area  originally  involved.  The  dead  tissue 
may  lie  in  an  abscess  cavity  formed  by  the  lesser  omentum,  or  in  rare 
instances  the  suppurative  and  necrotic  process  penetrates  the  intestine 


.  .r--^. 


Fig.  371. — Acute  Pancreatitis  with  Fat-necrosis  (Douglas). 
This  section  of  the  pancreas,  duct  of  VVirsung,  and  bile-duct  makes  evident  the  ease  with  which  the  bile  may  enter 
the  pancreatic  duct  when  a  stone  becomes  lodged  in  the  papilla,  below  the  junction  of  the  common  bile-duct 
and  the  duct  of  VVirsung.  Retrojection  of  bile  into  the  duct  of  the  pancreas  is  a  most  important  factor  in  the 
production  of  pancreatitis.  A.  Areas  of  fat-necrosis  upon  the  surface  of  the  pancreas.  B.  .Areas  of  fat- 
necrosis  within  the  parenchyma  of  the  gland.  C.  Ductus  communis  choledochus.  D.  Ductus  pancreaticus. 
E.  Papilla  of  Vater,  opening  of  the  ducts  into  the  duodenum  by  a  common  aperture  after  junction  just  above. 


into  which  it  empties.  Acute  inflammation  of  the  pancreas  is  frequently 
associated  with,  and  is  usually  due  to,  cholelithiasis  and  inflammatory 
conditions  affecting  the  bile-ducts.  The  splenic  enlargement  observed 
in  some  cases  may  have  arisen  independently  of  the  pancreatic  lesions 
or  was  the  result  of  sepsis.  Thrombosis  of  the  splenic  vein  sometimes 
follows  the  pancreatic  lesion  and  is  of  septic  origin. 

Acute  suppurative  pancreatitis  assumes  a  number  of  forms,  depend- 
ing upon  the  source  of  infection  and  the  presence  or  absence  of  pre- 
vious disease  of  the  organ.     It  may  be  a  part  of  a  general  sepsis,  in  which 


PAN'CKFvAS. 


771 


case  the  multiple  abscesses  scattered  throuj^'h  the  organ  are,  of  course, 
due  to  the  deposit  of  infected  emboli.  In  other  cases  the  suppurative 
process  is  restricted  to  the  pancreas,  and  may  be  secondary  to,  or 
really  a  part  of,  the  acute  hemorrhagic  or  gangrenous  pancreatitis 
already  described.  The  lesion  may  be  multii)le;  a  single  massive  abscess 
or  one  of  considerable  size  may  result  from  confluence  of  many  smaller 
abscesses.  In  the  suppurative  pancreatitis  not  preceded  by  the  hemor- 
rhagic lesion,  fat  necrosis  is  inconspicuous  or  absent.  The  abscesses 
may  penetrate  the  abdominal  cavity,  giving  rise  to  general  septic 
peritonitis;    or  they  may  be  evacuated  through  the  stomach  or  intes- 


372. — l-AT-NECROSI^    .\i  I  'iMrANYINT,    .\i~l'TF    1 1 IM' >K  R  11  A' .K"    I'ANXREATITIS. 

The  Jirea  shown  in  the  illustration  is  from  just  beneath  the  investing  tibrous  tissue  of  the  pancreas.  (For  descrip- 
tion of  process  sec  pane  253.)  A.  Maricin  of  area  of  hemorrhaKe.  B.  Kragmcntcfi  nuclei  in  area  of  necrosis. 
C,  C.  rat-cells  that  have  escaped  destruction.  Many  other  unaffected  or  but  slightly  changed  fat-cells  are 
present.  D.  Fat-cell  in  which  the  necrosis  is  not  complete.  E,  E.  .-Vrcas  in  which  the  necrosis  is  practically 
complete      F.  Part  of  pcripancrcatic  tibrous  tissue. 


tine;  it  is  possible  that  a  small  purulent  collection  may  inspissate.  The 
author  has  seen  what  he  believes  to  have  been  such  a  condition.  The 
suppurative  process  may  be  more  or  less  chronic  in  point  of  time,  and 
sometimes  induces  a  varying  amount  of  fibroid  change  in  the  gland 
structure. 

Chronic  pancreatitis,  pancreatic  sclerosis,  indurative  pancreatitis ,  and 
pancreatic  fibrosis  are  names  given  to  a  chronic  process  involving  the 
pancreas  and  associated  with  the  formation  of  a  noteworthy  amount 
of  fibrous  tissue. 


772 


SPECIAL  PATHOLOGY. 


B 


Causes. — The  lesion  may  be  congenital  or  may  be  seen  so  soon  after 
birth  as  to  lead  to  the  belief  that  it  must  have  been  in  progress  during 
intra-uterine  Hfe.  Such  fibroid  changes  are  probably  secondary  to  con- 
genital syphilis.  The  cause  of  the  lesion  in  adult  and  middle  life,  after 
which  time  it  becomes  more  conspicuous,  is  probably  duodenal  catarrh 
and  subacute  or  chronic  catarrhal  inflammation  of  the  pancreatic 
ducts.  The  changes  observed  by  Hoppe-Seyler^  in  the  arteriosclerotic 
pancreas  properly  belong  with  this  group. 

Morbid  Anatomy. — The  amount  of  fibrous  tissue  may  be  such  as 
distinctly  to  increase  the  size  of  the  organ.  In  most  cases,  however, 
there  is  contraction,  with  atrophy  of  the  glandular  structures,  and  in- 
duration of  the  entire  organ,  or  only  a  part  of  the  pancreas  may  be  in- 
volved.    The  tissue  resists  incision,  and  may  be  sufficiently  fibroid  to 

creak  under  the  knife. 
Occasionally  it  is 
calcareous.  The  duct 
may  be  normal  or 
dilated.  The  pan- 
creas is  sometimes  re- 
duced to  one-fourth 
or  one-fifth  of  its  nor- 
mal weight.  His- 
tologic examination 
of  the  organ,  when 
chronic  interstitial 
inflammation  is  pres- 
ent, discloses  a  nota- 
ble increase  in  the 
interstitial  tissue.  In" 
some  cases  it  may 
be  possible  to  surmise 
the  origin  of  the  con- 
dition by  the  location 
of  the  added  fibrous 
tissue.  When  the 
irritation  giving  rise 
to  the  fibrosis  has  re- 
sulted from  obstruc- 
tive lesions  in  the 
ducts,  the  sclerosis  is 
most  marked  around  these  structures.  In  the  older  areas  the  fibrous 
tissue  is  dense ;  when  the  lesion  is  progressing,  the  new  tissue  is  cellular, 
containing  lymphoid  and  plasma  cells  and  sometimes  eosinophiles.  Opie 
distinguishes  a  chronic  interlobular  pancreatitis  in  which  the  new  tissue 
is  most  conspicuous  between  and  around  the  lobule,  not  affecting  the 
islands  of  Langerhans;  at  most  these  structures  are  involved  late,  often 
after  the  acini  are  almost  entirely  destroyed.  The  second  form  described 
by  Opie,  he  calls  chronic  interacinar  pancreatitis.  In  this  type  the  scle- 
rosis around  the  lobules  is  less  marked,  the  fibrosis  contiguous  to  the 
islands  of  Langerhans  is  intense,  and  within  the  latter  structures  con- 


A  A 

Fig.  373.— Pancreas  Showing  Increase  of  Fibrous  Tissue.  Chronic 
Interstitial  Pancreatitis. 

A,  A.  Areas  of  hemorrhage.  B,B.  Immature  gland  cells  (bodies  of  Langer- 
hans). C.  Gland  acinus.  D,  D.  D,  D,  D.  Fibrous  tissue;  the  areas 
of  rhexis  (A,  A)  are  also  in  the  fibrous  tissue.  (From  a  case  of  congeni- 
tal syphilis.) 


'  "Deut.  Arch.  f.  klin.  Med.,"  Pd.  Ixxxi,  p.  119. 


PANCRKAS.  773 

nective-tissue  proliferation  also  occurs.  Pcarce'  has  shown  that  the 
islands  of  Lani^erhans  are  unaffected  by  the  advanced  interstitial  chanj^e 
occurrint,'  in  the  chronic  pancreatitis  due  to  congenital  syphilis. 

Pancreatic  calculi-  are  produced  by  causes  similar  to  those  opera- 
tive in  the  formation  of  gall-stones.  As  the  pancreas  possesses  two 
ducts,  obstruction  and  consequent  stone  formation  are  less  frequent. 
The  calculi  are  oval  or  elongated,  and  sometimes  branched,  like  coral. 
In  the  case  reported  by  Schu])mann  the  concretion  was  6  cm.  long  and  i 
cm.  thick;  300  have  been  observed  in  one  case.  They  are  composed 
of  cellular  detritus,  phosphate,  and  also  carbonate  of  lime,  and  often 
contain  bacteria.  In  seventy-two  cases  of  diabetes  studied  by  Hanse- 
mann  pancreatic  calculi  were  present  in  twelve.  They  may  give  rise 
to  abscess  formation  and  sinuses  and  be  discharged  e.Kternally.  The 
associated  obstruction  and  inflammation  of  the  duct  often  induce  a 
chronic  interstitial  pancreatitis. 

Syphilis  of  the  pancreas'  is  not  a  common  aflfection.  The  chronic 
pancreatitis  of  hereditary  syphilis  I  have  described  above.  Accom- 
panying that  form  of  lues  gummata  are  occasionally  observed.  Syph- 
ilitic endarteritis  may  produce  sclerosis  in  the  adult  pancreas.  Ter- 
tiary syphilis  is  sometimes  manifested  by  the  presence  of  syphilomata, 
which  may  obstruct  the  pancreatic  duct  or  bile-duct ;  Trinkler  suggests 
that  this  is  the  cause  of  jaundice  occasionally  seen  in  syphilis. 

Tuberculosis  of  the  pancreas  is  infrequent  and  probably  is  never 
primary.  In  disseminated  miliary  tuberculosis  the  pancreas  is  not 
always  affected,  and  even  when  tubercles  are  present,  they  are  rarely 
abundant.  Caseous  areas  are  sometimes  found,  and  extending  tuber- 
culosis of  contiguous  lymph-nodes  may  penetrate  the  organ. 

Tumors  of  the  pancreas^  are  uncommon;  in  13,000  autopsies  there 
were  133  cancers,  2  sarcomata,  i  adenoma,  2  cysts,  and  i  syphiloma. 
The  most  important  of  these  tumors  are  the  carcinomata,  which  may 
be  primary  or  secondary.  It  is  probable  that  most  of  the  primary 
cancers  begin  in  the  head  of  the  organ,  although  at  autopsy  practically 
all  of  the  pancreas  is  often  involved.  In  many  of  the  cases  it  is  impos- 
sible to  determine  the  exact  origin^  of  the  neoplasm;  the  definitely 
cylindric-cell  epitheliomata  probably  arise  from  the  ducts;  the  glandular 
cancers  are  presumably  from  the  epithelium  of  the  acini.  Carcinomata 
of  the  scirrhous  type  are  probably  the  most  frequent.  Secondary  car- 
cinomata of  the  pancreas  result  from  extension  of  primary  growths 
situated  in  the  stomach,  duodenum,  the  ampulla,  or  biliary  ducts. 
Metastases  by  the  blood  and  lymph  streams  are  less  common.  The 
occurrence  of  diabetes  in  pancreatic  cancer  is  attributed  to  neoplastic 
destruction  of  the  islands  of  Langerhans." 

Cysts  of  the  pancreas''  are  divided  into  those  arising  within  the  gland 

'  "Amer.  Med.."  Dec.  26,  1903,  also  "Albany  Med.  Annals,"  Jan.,  1904,  p.  88. 

*  Moynihan,  "Lancet,"  Aug.  9,  1902,  p.  355.     See  also  Pende,  "Policlinico." 
1905,  p.  112.  and  "La  Presse  M^d.,"  April  8,  19015,  p.  224. 

'Trinkler,  "Deut.  Zeit.  f.  Chir.,"  Bd.  Ix.w. 

*  NichoUs,  "Jour,  of  Med.  Research,"  1902,  vol.  viii,  No.  2,  p.  385. 
'  Falozzi,  "Ziegler's  Beitr.,"  Bd.  xxxiv,  H.  2,  p.  199. 

*  Pearce,  "Amer.  Jour,  of  Med.  Sci.,"  Sept.,  1904,  p.  478. 

'  Park.  "Amer.  Med.,"  June  13.  1903,  p.  949.  Lazarus,  "Zeit.  f.  klin.  Med.." 
1904,  vol.  li.  Gouraud,  "Gaz.  des  H6p.  Civils  et  Militaires,"  April  2,  1904.  Rob- 
son,  "Lancet,"  April  2,  1904,  p.  911. 


774  SPECIAL  PATHOLOGY. 

— true  pancreatic  cysts — and  cysts  situated  in  the  neighborhood  of 
the  pancreas — pseudopancreatic  cysts.  The  first  of  these  include  the 
retention  cyst, — pancreatic  ranula, — congenital  cystic  disease  of  the 
pancreas,  cystadenoma  of  the  pancreas,  and  hydatid  cysts  involving 
the  organ.  Pancreatic  ranula  ma}^  develop  as  a  monolocular  cyst,  near 
the  duodenum,  or  a  series  of  dilatations  distributed  along  the  duct  of 
Wirsung.  If  the  pancreas  possess  its  normal  number  of  ducts,  a  reten- 
tion cyst  is  rarely  formed.  Small  cysts  occupying  the  lobules  of  the 
organ — acne  pancreatica — result  from  obstruction  of  the  smaller  ducts. 
Congenital  cystic  disease  of  the  pancreas  is  a  rare  affection,  often  as- 
sociated with  similar  formations  in  the  kidneys  and  liver.  The  cause 
of  the  condition  is  unknown;  the  cysts  are  usually  multilocular,  and 
the  entire  organ  maybe  involved.  Cystadenomata  (p.  368)  are  definite 
neoplasms  of  the  pancreas  and  are  rare ;  the  cavities  may  contain  pap- 
illary masses  and  but  little  fluid.  Pseudopancreatic  cysts  result  from 
liquefaction  necrosis,  hemorrhage  in  noninflammatory  exudates  situated 
in  the  peripancreatic  tissues,  and  include  fluid  accumulations  in  the 
lesser  peritoneal  cavity.  Some  of  the  pseudocysts  communicate  with 
the  pancreas,  and  probably  a  few  of  them  are  the  direct  consequence 
of  pancreatic  disease.  They  are  frequently  the  result  of  injury,  and 
when  due  to  this  cause,  are  called  traumatic  pancreatic  cysts.  The  con- 
tained fluid  is  highly  albuminous  and  often  bloody.  Cysts  arising  from 
or  communicating  with  the  pancreas  usually  contain  one  or  more  of  the 
digestive  ferments  manufactured  by  the  organ.  In  the  case  reported 
by  Phillips  the  fluid  was  clear  and  possessed  a  speciflc  gravity  of  1.002, 
which  is  exceptionally  |low.  It  is  usually  brown  or  chocolate  colored, 
sometimes  contains  clots  of  blood,  and  is  nearly  always  alkaline  in 
reaction. 


CHAPTER  XI 11. 

DUCTLESS    GLANDS. 

THYROID   GLAND.' 

Normal  Histology.' — The  thyroid  gland  as  found  in  the  adult  is  com- 
posed of  vesicles  or  follicles,  round  or  oval,  measuring  fromjf35  m  to 
125  !i  in  diameter.  The  epithelial  wall  of  the  follicle  is  formed  by  a 
single  layer  of  columnar  epithelium.  These  cells  vary  in  height,  and 
are  placed  directly  upon  a  slightly  condensed  connective-tissue  layer, 
which  does  not  possess  the  usual  characters  of  a  basement  membrane. 
The  follicles  contain  a  homogeneous  colloid  body,  which  gives  slightly 
different  reactions  even  in  adjacent  follicles,  constituting  two  forms  of 
the  substance,  known  as  clear  and  dark  colloid.  There  is  an  unusually 
rich  supply  of  blood-vessels  and  lymphatics  in  the  surrounding  con- 
nective tissue.  Sometimes  lying  within  the  thyroid,  and  at  other  times 
some  distance  away,  are  bodies  resembling  embryonic  thyroid  tissue, 
and  composed  of  epithelium  arranged  in  columns,  but  not  forming 
distinct  follicles,  sacs,  or  tubes,  and  containing  no  characteristic  colloid 
substance.  That  these  bodies  are  not  simply  accessory,  immature,  or 
imperfectly  formed  thyroid  elements  is  indicated  by  the  fact  that  their 
development  is  completed  before  that  of  the  thyroid  gland.  Experi- 
mental evidence  goes  to  show  that  they  may,  however,  assume  some 
of  the  characters  of  the  normal  gland,  and  possibly  part  of  its  function, 
especially  when  the  latter  has  been  removed  or  destroyed.  These  bodies 
are  known  as  parathyroids.  The  number  of  parathyroids  varies,  rarely, 
however,  exceeding  four.  The  fact  that  the  removal  of  the  thyroid 
gland  induces  changes  reseml)ling  those  seen  after  the  removal  of  the 
parathyroids  would  further  indicate  that  the  function  of  the  latter  is 
accessory  or  compensatory  to  the  former,  and  in  man,  as  well  as  in 
lower  animals,  the  removal  of  the  thyroid  may  not  be  followed  by  symp- 
toms, the  parathyroids  assuming  the  functions  of  the  removed  gland. 

Malposition  and  Malformation  of  the  Thyroid. — The  gland  may  be 
absent;  onlv  one  lobe  is  sometimes  present.  The  isthmus  is  frequently 
abnormal;  it  occasionally  consists  of  a  narrow  band  of  fibrous  tissue 
in  which  there  is  no  thyroid  structure.  In  other  instances  it  forms 
the  base  of  a  pyramidal  lobe  extending  upward  along  the  anterior  sur- 
face of  the  trachea,  following  the  course  of  the  normally  obsolescent 
duct;    along  the  course  of  the  latter  structure  irregular  masses  of  thy- 

'  For  recent  exhaustive  studyof  patholot^'of  tlic  thyroid  see  Diul.cjeon,  "Trans, 
of  Path.  Soc.  of  London."  vol.  I'v,  p.  151.  Also  Edmunds.  "Lancet.'"  iqoi.  vol.  i.^ 
For  recent  clinical  treatise  consult  Richardson,  "The  Thyroid  and  Parathyroids," 

1904-  „ 

'  For  recent  studies  see  Flint.  "  Amer.  Jour,  of  Anat.."  Dec.  1Q04.  p.  77.  For 
recent  review  of  physiology  of  the  thyroid  and  parathyroids  see  Vincent  and  Jolly. 
"Jour,  of  Physiol.."  1904.  xxxiii.  p.  65;  also  Kishi,  "Virchow's  Arch..  '  1904,  Bd. 
176,  p.  260. 


776 


SPECIAL  PATHOLOGY. 


roid  tissue  are  sometimes  present.  Aberrant  masses  of  thyroid  tissue 
are  occasionally  observed;  they  may  be  along  the  track  of  the  thyro- 
glossal  duct,  in  the  tracheal  submucosa  (p.  575),  in  the  submaxillary 
region,  on  the  floor  of  the  mouth,  in  the  mediastinum,  and  at  almost  any 
point  in  the  neck.  The  aberrant  thyroid  tissue  may  represent  the 
entire  gland,  and  hence  should  not  be  removed  until  the  surgeon  has 
assured  himself  that  other  thyroid  tissue  is  present.^  Such  misplaced 
thyroids  may  give  rise  to  ectopic  goiter — lingual  goiter,  tracheal  goiter,^ 
submaxillary  goiter,  and  mediastinal  goiter.  The  thyroglossal  duct 
may  persist^  and,  if  patulous,  constitutes  a  thyroglossal  fistula;  when 
closed  at  both  ends,  a  cavity  containing  modified  thyroid  secretion,  and 


Fig.  374. — Thyroid  Gland,  Absence  of  Isthmus. — 
(Marshall,  courtesy  oj  Dr  Richardson.) 


Fig.  375- — Thyroid  Gland  Large  Pyramid,  So- 
called  Pyramidal  Lobe. — {Marshall,  courtesy 
of  Dr.  Richardson.) 


called  a  thyroglossal  cyst,  occasionally  develops.  Abnormally  placed 
goiters,  which  undergo  carcinomatous  transformation,  are  known  as 
ectopic  thyroid  cancers.  Absence,  atrophy  or  ectopia  of  the  thyroid  is 
occasionallv  accompanied  by  enlargement  of  the  parathyroid. 

Anemia,  Hyperemia,  and  Congestion  of   the   Thyroid. — Of  a  purely 

^  See  discussion  bv  Paton  and  also  Spencer,  Clin.  Soc.  of  London,  Feb.  10, 
1905;    "Brit.  Med.  Jour.,"  Feb.  18,  1905,  p.  357. 

2  Ferguson,  "N.  Y.  Med.  Jour.,"  Aug.  13,  1904,  p.  289. 

'  Riesman,  "Amer.  Med.,"  June  29,  1901.  Comil  and  Schwartz,  "  Revtie  de 
Chir.,"  Dec.   10,  1904,  p.  717. 


DUCTLKSS   GLANDS. 


777 


local  anemia  involvinj,'  the  thyroid  but  little  is  known.  Hyperemia  is 
present  in  acute  inflammatory  processes,  aside  from  which  we  have  also 
an  unusual  vascular  congestion,  partly  hyperemic  and  partly  conges- 
tive, constituting  the  so-called  vascular  goiter.  Congestion  of  the 
thyroid  may  be  a  jiart  of  the  general  venous  distention  occurring  in 
cardiac  diseases  with  failing  circulation.  There  is  also  evidence  of  its 
jirescnce,  as  ])reviously  indicated,  in  vascular  goiter. 

Atrophy  of  the  thyroid  undoul)tedly  occurs,  but  the  exact  factors 
influential  in  establishing  this  condition  are  but  poorly  understood. 
It  is  not  improbable  that  inflammatory  and  productive  processes  in- 
duce a  sclerosis  analogous  to  that  seen  in  other  secreting  organs  with 
which  we  are  more  familiar.     In  further  support  of  this  view  is  the 


l^ 


Fig.  376. — Thyroid  Gi.ASD  Showtnt,  Double  Pyra- 
mid.— {Marshall,  courUsy  oj  Dr.  Richardson.) 


Imc.  377. — Thyroid  Gland,  Absence  of  Isthmus 
WITH  Pyramid  on  Left  Side.  —  (Marshall, 
courtesy  oj  Dr.  Richardson.) 


well-known  fact  that  occasionally  cases  of  thyroid  enlargement  associated 
with  exophthalmos,  tremors,  and  rapid  cardiac  action  (Graves's  disease) 
show  a  progressive  diminution  in  the  size  of  the  thyroid,  which  after- 
ward remains  small.  The  phenomena  brought  about  by  ])rogressive 
atrophy  of  the  organ  usually  are  identical  with  those  seen  after  the 
removal  of  the  thyroid  gland,  the  results  of  which  have  been  studied 
in  man,  monkeys,  and  other  animals. 

The  phenomena  occurring  in  the  patient  are  somewhat  ditTerent 
when  the  thyroid  gland  has  never  been  present — a  condition  constitut- 
ing sporadic  cretinism,  or  congenital  myxedema. 

The  general  di.sturl)anccs  uf  nutrition  and  arrest  of  development 
are  usuallv  not  evident  at  birth,  but  commonlv  manifest  themselves 


y-8  SPECIAL  PATHOLOGY. 

within  the  first  year.  The  stunted  growth,  which  particularly  involves 
the  long  bones,' associated  with  thickening  of  the  cranial  bones,  mus- 
cular weakness,  intellectual  deficiency,  overgrowth  of  the  subcuta- 
neous tissue, — which  may  be  myxedematous, — with  yellowish,  dry  skin, 
brittle,  scanty  hair,  protruding  lips,  thickened  tongue,  and  more  or  less 
salivation,  comprise  the  clinical  and  pathologic  picture.  Cretins  rarely 
attain  a  height  of  five  feet,  and  sometimes  do  not  exceed  three  feet. 

Closely  resembling  the  condition  just  mentioned  are  the  tissue  and 
nutritive '  changes  resulting  from  destructive  processes  attacking  the 
thvroid  gland.  The  destruction  may  be  due  to  the  occurrence  of  cysts, 
to 'fibrous  deposits,  or  to  tumor  invasion,  and  constitutes  a  part  of  the 
anatomic  basis  of  the  disease  called  myxedema.^  Myxedema  usually 
occurs  later  in  life;  ninety  per  cent,  of  the  cases  are  in  women.  The 
tissue  changes  resemble  those  seen  in  sporadic  cretinism,  except  that  the 


'/ 


Fig.  378. — IxTRATH0R.4ac  Goiter  Developed  from  Ectopic  Thyroid. — {Diltrich,  courtesy  oj  Dr.  Richardson. 

further  development  of  the  body,  which  may  be  completed,  considerably 
alters  the  picture.  There  is  a  more  conspicuous  thickening  of  the  subcu- 
taneous tissues,  with  dry,  rough,  or  scaly  skin,  broad  and  flattened  digits, 
thick  and  overhanging  lips,  mental  dullness,  and  evident  poor  nutrition 
of  the  hair,  already  mentioned  as  present  in  cretinism.  The  mucous 
membranes  and  submucous  tissues  show  changes  resembhng  those  noted 

1  Millet.  "Boston  Med.  and  Surg.  Jour.,"  Oct.  10,  1901.  AbrikossofY,  "Vir- 
chow's  Arch.,"  Sept.  i.  1904.  Bd.  177.  p.  426.  Russell,  "Johns  Hopkins  Hosp. 
Biill.,"  June.  1904.  Lanz,  "Arch.  f.  klin.  Chir.,"  vol.  74,  No.  4.  Thyroid  aplasia 
and  infantile  myxedema  see  Pineles,  "Wien.  klin.  Woch.,"  Oct.  23,  1902,  p.  1129. 
Changes  in  the  "central  nervous  system  in  cretins,  see  Bayon,  "  Neurolog.  Cen- 
tralbl.,"  April  16,  1904.  For  the  relation  of  thyroid  inadequacy  to  eclampsia 
see  Nicholson,  "Brit.  Med.  Jour.,"  Oct.  11,  1902,  p.  1138;  also  Stunner,  "Jour, 
of  Obstet.  of  the  British  Empire,"  June,  1904.  The  occurrence  of  myxedema  in 
calves,  consult  Seligmann,  "Jour,  of  Path,  and  Bact.,"  March,  1904,  p.  311. 


nrCTI.ESS   ('.LANDS. 


779 


in  tlie  skin.  There  is  submucous  tumefaction,  |)articularly  marked  in 
the  hps.  mouth,  and  tongue,  and  sometimes  in  the  ])alate.  (See  p.  247.) 
The  teeth  become  carious,  and  sometimes  fall  out.  It  is  well  known 
that  absence  of  the  thyroid  is  commonly  associated  with  mental  hebetude, 
and  consequently  one  would  expect  to  find  important  histoloj^ic  changes 
in  the  central  nervous  system;  the  structural  alterations  observed,  how- 
ever, are  not  always  the  same,  nor  are  they  constantly  [present.  Bayon 
described  hyaline  changes  in  the  vessels  of  the  cortex  without  conspicuous 
abnormality  in  the  ganglion  cells;  other  observers  mention  vacuoliza- 
tion, pigment  changes  in  the  Nissl  bodies  (tii^roivsis),  and  alterations  in 
the  chromatin  (chroniatolysis)  of  the  ganglion  cells;  edema  and  occa- 
sionall\'  hemorrhage  mav  be  |irescnt. 

Cachexia  Strumipriva  (Postopera- 
tive Myxedema). — As  a  result  of  the 
clinical  observations  of  Kocher, 
Revenlin,  and  others,  and  the  ex- 
perimental research  of  Horsley,  Ed- 
munds and  Vassale,  and  Generali,  it 
has  been  found  that  total  ablation 
of  the  thyroid  is  followed  by  phe- 
nomena resembling  those  seen  in 
cretinism  and  myxedema.  The  oc- 
currence of  this  condition  is  depen- 
dent upon  the  more  or  less  complete 
removal  of  the  thyroid  and  para- 
thyroids; the  resulting  disease  is 
evidently  due  to  the  absence  of 
thyroid  function,  as  indicated  by 
the  fact  that  grafting  of  thyroids 
into  thyroidectomized  animals  leads 
to  the  disappearance  of  the  symp- 
toms, and.  further,  that  the  admin- 
istration of  thyroid  extract  in  this 
condition,  as  well  as  in  cretinism 
and  myxedema,  arrests,  or  at  least 
greatly  modifies,  the  diseases  in 
question.  Apparently,  these  condi- 
tions are  due  to  thyroid  inactivity, 
insufficiency,  or  absence — and  are 
correctly   included  under  the  term 

athyroidism,  for  which  term  athyrosis,  athyroidation,  and  athyroidca  are 
used  synonymously. 

Hypertrophy  of  the  thyroid  will  be  considered  with  goiters  and  tumors 
of  the  gland. 

Infiltrations  and  Degenerations. — Aside  from  the  occasional  presence 
of  calcareous  material  in  the  thyroid  gland,  as  well  as  hyaline  substances 
and  bodies  resembling  lardaceous  material,  nothing  is  known  of  the 
special  forms  of  infiltration  and  degeneration  occurring  in  this  organ. 
Atrophied  and  fibroid  thyroids  frequently  contain  an  excess  of  adipose 
tissue,  the  deposit  of  which  appears  to  be  distinctly  secondary  to  the  loss 
of  gland-substance.  Degenerative  changes  are  constantly  present  in  the 
epithelium  lining  the  follicles;  their  significance,  however,  is  not  at 
present  appreciated. 


Fig.  .170. — Cretin  Aged  T\venty-two  Years. — 
(Wtigncr,  courtesy  of  Dr.  Richardson.) 


780  SPECIAL  PATHOLOGY. 

Of  thyroiditis,  strumitis,^  or  inflammation  of  tlie  thyroid  gland,  but 
little  is  known;  in  various  infections  and  toxic  conditions  an  acute 
nonsuppurative  thyroiditis'-  has  been  observed.  The  colloid  is  increased, 
proliferation  and  necrosis  of  the  gland  cells  occur,  the  interstitial  tissues 
are  edematous  and  may  contain  a  few  leukocytes,  of  the  mononuclear 
types,  and  hemorrhagic  lesions  are  sometimes  present.  Roger  and 
Garnier  give  35  gm.  as  the  normal  weight  of  the  thyroid;  in  the  acute 
nonsuppurative  inflammations  the  gland  sometimes  weighs  50  gm.  to 
55  gm.  The  condition  is  more  frequent  in  infants  than  in  adults,  and 
has  been  studied  particularly  in  variola.  Acute  suppurative  strumitis,^ 
also  called  acute  purulent  strumitis,  may  be  diffuse  or  localized;  the 
latter  is  called  thyroid  abscess.  The  causative  bacteria  may  reach  the 
gland  from  contiguous  structures  or  by  the  blood ;  the  latter  form  of  the 
infection  occurs  in  pyemia  and  usually  gives  rise  to  multiple  abscesses. 
Thyroid  suppuration  occurring  in  the  course,  or  as  a  sequel,  of  an  in- 
fectious disease,  especially  typhoid,  is  due  to  hematogenous  infection. 
In  both  the  diffused  and  circumscribed  suppurations  the  organ  is  en- 
larged, tender,  and  edematous.  When  the  infection  is  diffuse,  poly- 
morphonuclear leukocytes  are  abundant  in  the  interstitial  tissue  and 
may  penetrate  the  acini  in  large  numbers.  A  chronic  fibroid  inter- 
stitial thyroiditis*  has  been  described;  it  may  be  diffuse  in  the  inter- 
stitial tissue,  or  restricted  to  smaller  areas  (insular  thyroid  sclerosis). 
In  some  cases  the  gland  acini  are  enlarged  or  even  cystic;  in  other 
instances  the  vesicles  are  small  and  the  epithelium  wasted;  the  latter 
type  corresponds  to  the  diffuse  sclerosis  mentioned  when  discussing 
atrophy  of  the  organ. 

Tuberculosis  of  the  thyroid''  may  be  primary  or  secondary.  The 
former  is  usually  characterized  by  the  presence  of  caseous  or  fibrocaseous 
areas  in  the  gland,  and  is  exceedingly  rare.  Secondary  tuberculosis  may 
result  from  extension  of  lesions  primary  in  adjacent  structures,  es- 
pecially the  lymph-nodes,  or  hematogenous  dissemination  of  the  bacil- 
lus, particularly  in  miliary  tuberculosis.  The  tubercle  bacillus  rarely 
colonizes  in  the  thyroid  gland;  Lebert  observed  tuberculosis  of  this 
organ  in  7  per  cent,  and  Frankel  in  12  per  cent,  of  the  tuberculous 
cadavers  examined. 

Syphilis  of  the  thyroid  is  exceedingly  rare:  the  cause  of  the  swelling 
sometimes  seen  in  secondary  syphilis  remains  undetermined.  Gumma 
occasionally  occurs.  A  nodular  enlargement  in  congenital  syphilis^ 
has  been  described. 

Goiter,  struma,  and  hronchocele  are  terms  applied  to  certain  thyroid 

^  The  term  strumitis  is  often  used  for  inflammation  occurring  in  a  goiter;  the 
changes  are  essentially  similar  to  those  observed  in  the  previously  normal  thyroid, 
and  attempts  to  distingviish  the  two  processes  have  been  unproductive. 

^  Roger  and  Garnier,  "La  Presse  Med.,"  May  16,  1903,  p.  373,  and  "Virchow's 
Arch.,"  1903,  Bd.  174,  p.  14.  Bayon,  "Centralbl.  f.  allg.  Path.,"  Sept.  30,  1904, 
p.  737.  de  Quervain,  "  Mittheilungen  a.  d.  Grenzgebiet.  de  Med.  u.  Chir.,"  1904, 
Bd.  13,  H.  4  and  5,  second  supplementary  band. 

^  Deleuil.  "These  de  Lyon,"  1902.  Abrajanofif,  "Chirurgia,"  Feb.,  1903. 
Krause,  "Berl.  klin.  Woch.,"  Aitg.  17,  1903,  p.  756. 

*  E.  Perrin  de  le  Touche  and  Marrice  Dide,  "Soc.  de  Neurol.,"  Paris,  Nov.  5, 
1903;    "Revue  Neuro.,"  Nov.  30,  1903,  p.   1120. 

'  Clairmont,  "Wten.  klin.  Woch.,"  Nov.  27,  1902.  Pupovac,  "Wien.  klin. 
Woch.,"  Sept.  3,  1903,  p.  1012. 

*  Goulon,  "Arch,  de  Med.  des  Enfants,"  1904,  vii,  p.  36. 


DUCTLESS  GLANDS. 


781 


enlargements  ot  obscure  origin.     The  condition  is  fiidemic  in  Switzer- 
land, certain  parts  of  France  and  Italy,  and  goitrous  centers  have  been 
observed  in  the  United  States  (Michigan,  Pennsylvania).     The  affection 
has  been  attributed  to  causes  arising  in  both  water  and  soil,  and  also 
to  atmospheric  conditions.     The  recent  studies  of  Grassi  and  Munaron' 
indicate  that  goiter  is   due    to    poisons  elaborated  by   some  organism 
inhabiting  the  soil  and   living  outside  of   the   liuman   Imdy.      Several 
varieties  of  the  affection  are  recognized.     In  parenchymatous  goiter  the 
affected  tissue  possesses  a  structure  similar  to  that  of  the  normal  organ, 
although  empty  follicles 
and   hy{)erplasia  of   the 
interstitial   tissue  are 
more  abundant  than  in 
health.     It  is  supposed 
that    this    form    results 
from  an  increase  in  all 
the  gland  elements,  and 
hence    it    is    sometimes 
called    hyperplastic 
goiter.     In  colloid  goiter 
the   cavities  are   larger, 
the    walls  thinner,    and 
the    increase    in    inter- 
stitial   tissue    less    con- 
spicuous.    When   the 
dilated     gland    spaces 
attain  considerable  size, 
the   condition    is   some- 
times called  cystic   col- 
loid goiter.   In  this  form 
the    material    contained 
within    the    cavities    is 
unusually  rich  in  colloid 
and  in  some  cases  mucin 
is  present.    Calcification 
of  the  wall  occurs.     The 
cysts  are  lined  by  epi- 
thelium   which,    in    the 
earlier  stages,  is  distinct- 
ly of  the    low  columnar 
type,  but  later  becomes 
flattened,  granular,  and 
occasionally  fatty.     Fi- 
broid goiter  is   recognized  by  the   large  amount  of  fibrous  tissue  that 
it   contains.      The   newly   formed   fibrous    element    may    be   uniformly 
disseminated   throughout  the  mass,   or  grouped   in   islands  irregularly 
distributed  in  the  goiter;    the  latter  type  is  sometimes  called  nodular 
fibroid  goiter.     In   some  forms  of  struma  hemorrhages  into  the   cysts, 
or  interstitial   tissue,  occur,   and   in   a   way   justify   the   name  hemor- 
rhagic goiter.     In  other  cases  the  goitrous  enlargement  is  composed  of, 
or  contains  an  enormous   number  of   large  vessels,  usually  veins,  some 
'  "Rendiconti  d.  r.  Accad.  dei  Lincei."  Jan.  17,,  1904,  vol.  xiii.  p.  57. 


P 


'% 


Fic.  380. — U.NVsiALLY    Larlk.   Cystic   Goitkr. 
photograph.) 


(Redrnwn    from 


782 


SPECIAL  PATHOLOGY. 


of  which  formed  a  part  of  the  normal  gland  and  others  are  newly  de- 
veloped. This  condition  is  called  vascular  goiter,  or  telangiectatic 
goiter.  Goitrous  enlargements  of  the  thyroid  gland  may  inflame, 
suppurate,  undergo  necrosis,  or  calcify;  the  process  last  named  is  the 
result  of  calcific  deposit,  usually  in  the  stroma  of  the  mass.  Neoplastic 
goiters  consist  of  definite  tumors  involving  the  thyroid;  when  the  neo- 
plasms are  innocent,  the  enlargement  is  called  benign  goiter.  The  same 
term  is  also  applied  to  the  forms  of  thyroid  enlargement,  mentioned 
above,  which  are  generally  regarded  as  distinct  from  new  growths. 
When  sarcoma  or  carcinoma  involves  the  gland,  the  condition  is  called 

malignant  goiter. 

A  goiter  may  be  unilateral  or  bila- 
teral, or  involve  the  isthmus.  When 
arising  from  aberrant  thyroid  tissue, 
occupying  an  abnormal  location,  the 
term  aberrant  or  ectopic  goiter  is  some- 
times used;  as  a  rule,  however,  it  re- 
ceives its  name  from  the  position  that  it 
occupies — lingual  goiter,  tracheal  goiter, 
submaxillary  goiter,  mediastinal  goiter. 
With  regard  to  the  rapidity  with  which 
an  enlargement  develops  it  is  possible 
to  recognize  acute  and  chronic  goiters. 
In  the  simple  goiters  the  symptoms  pro- 
duced are  determined  by  the  influence 
of  the  growth  on  contiguous  tissues.  The 
large  vascular  trunks  and  nerves  of  the 
neck  may  be  pressed  upon,  or,  what  is 
more  common,  the  trachea  suffers.  It 
may  be  flattened  by  bilateral  or  median 
growths,  or,  when  the  goiter  is  unilateral 
or  one  lobe  is  most  affected,  be  displaced 
to  one  or  the  other  side.  The  lumen  is 
obstructed  by  an  annular  growth  or 
bilateral  pressure,  pressure  from  in  front 
or  the  development  of  a  thyroid  tumor 
in  the  submucosa  (intratracheal  goiter). 
Lingual  goiter  may  obstruct  the  pharynx 
or  encroach  upon  the  laryngeal  opening. 
Mediastinal  goiter  may  press  upon  the 
lower  trachea,  bronchi,  or  other  intrathoracic  structures. 

Exophthalmic  goiter,^  also  called  Graves's  disease,  or  Basedow's 
disease,  is  an  affection  of  unknown  etiology,  usually  characterized  by 
exophthalmos  (prominence  of  the  eyeballs),  tachycardia,  a  peculiar 
form  of  muscular  tremor,  and  enlargement  of  the  thyroid  gland;  one  or 
more  of  these  so-called  cardinal  symptoms  may  be  absent.  It  is  clearly 
an  intoxication — a  toxemia;  the  character  and  origin  of  the  poison  are 
not  definitely  known,  but  the  facts  at  our  disposal  indicate  that  it  is 

1  Kocher,  "  Ueber  Morbus  Basedowi,"  1902;  1423  references.  Murray,  "Lan- 
cet," Dec.  13,  1902,  p.  1612.  Salmon,  "Clin.  Med.,"  Aug.  3,  1904.  Jellinck, 
"Wien.  klin.  Woch.,"  Oct.  27,  1904.  MacCallum  and  Cornell,  "Med.  News," 
Oct.  15,  1904,  p.  732. 


Fig.  381. — Goiter  (Bilateral)  Causing 
Compression  of  the  Windpipe  Produc- 
ing THE  So-called  "Bayonet-shaped" 
Trachea. — {Demme,  courtesy  of  Dr. 
Richardson.) 


DUCTLI-;SS  f.LAxns. 


783 


some  prodiut,  normal  or  abnormal,  of  the  tliyroid  gland.  When  an 
excess  of  thvroid  secretion  is  absorbed,  symptoms  resembling  some 
featuri's  <if  (iravcs's  disease  may  occur,  and  constitute  what  is  called 
hyperthyroidism  or  thyroidismus;  these  phenomena  may  be  experi- 
mentallv  ])roduced,  follow  operations  in  which  thyroid  secretion  escapes 
into  the  wound,  or  be  due  to  other  injuries  of  the  gland.  In  Basedow's 
disease  the  blood  content  of  the  thyroid  is  increased,  and  hyperplasia  of 
the  epithelium  of  the  acini  is  usually  present,  although  there  is  no 
absolutely  constant  anatomic  alteration  in  the  gland.  MacCallum  and 
Cornell  conclude  that  no  adequate  explanation  has  been  given  for  the 
exophthalmos. 

Tumors  of  the  Thyroid. — 
Adenomata  are  occasionall\- 
observed;  they  are  usually 
single  and,  as  a  rule,  enca])- 
sulated;  they  are  sometimes 
cystic  with  papillary  growths 
in  the  interior  (papillary 
cystadenoma).  Low  Mias  been 
able  to  collect  ten  such  cases. 
Cancer-  of  the  thyroid  may  be 
])rimary  or  secondary.  The 
former  is  usually  encephaloid 
and  frequently  grows  rapidly, 
constituting  the  most  fatal 
form  of  malignant  goiter. 
Thyroid  carcinoma  is  most 
frequent  in  goitrous  glands; 
two-thirds  of  the  patients  are 
women.  In  the  earlier  stages 
the  growth  is  within  the 
capsule  of  the  organ,  but 
later  it  extends,  involving 
the  trachea  and  sometimes 
the  esophagus.  In  over  half 
the  cases  enlargement  of  the 
cervical  lymph-nodes  occurs. 
Secondary  cancer  involves 
the  organ  as  a  result  of  ex- 
tension of  a  primary  growth 
arising  in  the  larynx,  pharynx,  trachea,  branchial  vestige,  or  other  con- 
tiguous structure.  Fibromata,  chondromata,  and  osteomata  are  rare 
tumors  of  the  thvroid.  Sarcoma  is  an  infrequent  thyroid  tumor  occurring 
about  one-fourth  as  often  as  cancer;  of  the  tifty-three  cases  collated  by 
Lartigau,'  thirty-five  occurred  in  goitrous  glands.  Round  and  spindle,  or 
mixed  cell  sarcomata  are  the  most  common.  In  certain  tumors  of  the 
thyroid  it  is  impossible  to  decide  whether  the  growth  is  a  sarcoma  or 
a  carcinoma;  these  neoplasms  have  received  the  name  mixed  tumors' 
or  carcinosarcomata  of  the  thyroid. 

'  "Boston  Med.  and  Surg.  Jour.,"  Dec.  3,  1903. 
'  Delore.  "Rev.  de  Chir."  May  10,  1904,  p.  680. 
'   '.Amer.  Jour,  of  the  Med.  Sci,"  Aug..  iqoi. 
*  See  Loeb,  "Amer.  Jour   of  .Med.  Sci.,''  Feb..  1903. 


Fir..   382. 


-Exophthalmic  Goitf.r,   Basedow's  Disease. — 
{Courtesy  of  Dr.  Richardson .) 


784 


SPECIAL  PATHOLOGY 


Dermoid  cysts  in  the  thyroid  have  been  observed.  Hydatids^  of  the 
organ  occur,  but   are  extremely  rare;    twenty-five  cases  are  recorded. 

Thyroid  metastasis'-  is  an  extremely  interesting  condition  char- 
acterized by  the  development  of  new  growths  composed  of  typical 
thyroid  tissue  in  structures  distant  from  the  gland.  In  some  instances 
the  thyroid  is  not  enlarged.  The  tumors  are  usually  nonmalignant, 
and  as  a  rule  involve  bones.  In  7  of  the  18  reported  cases  the  cranium 
was  affected;  14  of  the  patients  were  women. 

SUPRARENALS.3 

Malformation  and  Malposition. — The  suprarenal  bodies  may  be 
absent  or  hyperplastic.  Accessory  bodies  may  occur.  The  supernum- 
erary bodies  may  be  near  their  normal  position,  or  they  may  be  in  the 
capsule  or  cortex  of  the  kidney,  in  or  near  the  internal  abdominal  ring, 


Fig.  383. — Section  of  Cortex  of  Kidney  Containing  Ectopic  Adrenal.      (Fixed  in  Heidenhain's  solution, 

paraffin,  hematoxylin  and  Van  Gieson    Obj.  i6  mm.,  oc.  compensation,  and  reduced  J.) 
^.  Capsule  of  kidney  extending  over  adrenal.    B,B,B.     Zona  glomerulosa.     C,C.     Zona  fasciculata.     D.  Zona 

reticvjaris.     E.  Capsule   projected  between  adrenal  and  kidney  cortex  partly  separating  the  two  structures. 

F.  Canty  surrounded  by  Bowman's  capsule,  external  to  which  is  adrenal  tissue.     G.  Large  vein.     H.  Kidney 

cortex.     '/.  Imperfectly  developed  Malpighian  body. 

inguinal  canal,  about  the  spermatic  cord,  in  the  epididymis  or  testicle, 
and  in  or  near  the  ovary  or  broad  ligament ;  they  are  also  occasionally 
found  in  the  liver.  Ectopic  suprarenal  cells  constitute  the  histologic 
elements  from  which  hypernephromata  (p.  662)  arise.  Occasionally 
one  or  both  the  glands  are  hypoplastic. 

^  Rollet,  These  de  Lyon,  1902  and  1903,  No.  163. 

^HoUis,  "Lancet,"  March  28,  1903,  p.  884.  Oderfeld  and  Steinhaus,  "Cen- 
tralbh  f.  allg.  Path.,"  1903,  vol.  xiv,  p.  84.  Patel,  "Rev.  de  Chir.,"  March  10, 
1904,  p.  398. 

2  For  review  of  development,  structure,  and  function  of  the  suprarenal,  see 
Minervini,  "Jour,  de  I'Anatomie,"  Sept.  and  Oct.,  1904.  For  recent  sttidy  of  the 
pathology  of  the  suprarenal,  see  Karakascheff,  "  Ziegler's  Beitr.,"  1904,  Bd.  36, 
p    401;   also,  Marchetti,  "Virchow's  Arch.,"  1904,  Bd.  177,  H.  2,  p.  227. 


DUCTLESS   (".LANDS. 


785 


Atrophy  of  the  suprarenals  is  somelimcs  associated  with  libroid 
chaiij^'o,  may  rtsult  lri»in  iiressure,  is  not  infrequently  marked  in  old 
age,  anil  occasionally  is  secondary  to  inllammatory  processes  occurring 
within  the  gland  or  in  the  contiguous  tissues.  A  simple  atrophy  has 
been  described  in  \\  Inch  it  is  stated  that  the  organs  are  no  larger  than 
I^eas. 

Hypertrophy  of  the  suprarenals  is  rare;  when  one  is  absent  or  hy- 
poplastic, or  has  l)ccn  destroyed  by  disease,  the  remaining  organ  may 
enlarge.  According  to  Marchetti,  the  hypertrophy  is  restricted  to  the 
cortex. 

Infiltration  of  the  Suprarenals. — A  gland  otherwise  normal  may  show 
a  small  amount  of  adventitious  pigmentation,  particularly  in  old  age. 
As  a  rule,  the  pigment  deposit  does  not  involve  the  whole  organ,  but  is 
restricted  to  one  or  more  layers  of  the  cortex,  extending,  to  a  certain 
degree,  into  the  ad- 
jacent medulla.  Lar- 
daceons  disease  may 
affect  the  blood-ves- 
sels and,  to  a  very 
limited  extent,  the 
connective  tissue  of 
the  organ;  the  iodin 
and  microchemic  re- 
actions (p.  230)  are 
best  seen  in  the  cor- 
tex. Calcareous  in- 
f,ltration  occurs  in 
chronic  infections 
that  involve  the 
gland,  and  is  not  in- 
frequently present 
without  any  evidence 
of  inflammation  or 
tuberculosis. 

Degeneration  of 
the  Suprarenals.  — 
Paroichymatons  and 
fatty     degenerations 

have  been   described,  but   little  is   known  of  their  etiology   or  course. 
The  former  is  frequently  observed  in  infectious  processes. 

Hemorrhage  into  the  suprarenals/  or  the  adjacent  fat,  may  result 
from  trauma  and  is  sunietimes  seen  m  intense  congestion.  It  is  particu- 
larly frequent  in  the  new-born  and  in  children.  Toxic  conditions, 
congenital  syphilis,  septicemia,  pyemia,  and  gastro-intestinal  infections 
proving  fatal,  are  often  associated  with  hemorrhagic  inhltration  of  the 
suprarenal.  It  is  not  known  how  these  conditions  induce  the  hemor- 
rhage; it  has  been  suggested  that  they  act  by  altering  the  endo- 
thelium of  the  ca[)illaries.  The  condition  is  also  called  suprarenal 
apoplexy  and  is  sometimes  seen  after  severe  burns,  in  which  case  it  is 
apparently  due  to  the  accompanying  toxemia.     It  may  be  diffuse  or 

'  In  addition  to  Marchetti  and  Karakascheff.  see  also  Dudgeon.  "Amer.  Jour, 
of  Med.  Sci."  Jan.,  1904,  p.  134,  and  Langmead.  "Lancet."  May  28.  1904,  p.  1496. 


lir..  384. — Section  <iv  l-.fTopir  Aurknai,  Henkath  thk  J'kritoneim  am> 

Lntimately  .\ttachkd  to  thk  Capsulk  of  the  Livek. 

.1 .  A .  Capsule  of  Gliss*jn.    B,  B.  Zona  glomcrulosa.    C,  C.  2k)na  fasciculala. 

D,  D.  Zona  reticulata.     E,  E.  Peritoneal  surface. 


786  SPECIAL  PATHOLOGY. 

punctate,  and  sometimes  forms  a  distinct  hematoma.  The  changes 
resulting  from  the  hemorrhage  are  not  understood.  It  is  possible  that 
chronic  fibroid  induration  or  cyst  formation  sometimes  results  from  the 
hemorrhage. 

Inflammation  of  the  suprarenal  may  assume  an  acute  or  a  chronic 
type.  Of  the  acute  form  but  little  is  known,  with  the  exception  of  an  oc- 
casional suppurative  lesion  secondary  to  infection  by  means  of  the  blood 
or  involvement  as  a  result  of  the  extension  of  infection  from  adjacent 
suppurative  processes.  In  the  chronic  form  induration  of  the  gland 
occurs,  brought  about  by  the  production  of  new  fibrous  tissue ;  the  lesion 
is,  therefore,  comparable  to  the  chronic  interstitial  inflammations  that 
involve  other  glandular  viscera.  Sergent^  has  described  a  chronic 
suprarenalitis  of  infectious  origin  and  attended  by  the  gradual  evolution 
of  suprarenal  insufficiency. 

S)rphilis  of  the  suprarenals  may  be  manifested  by  the  presence  of 
gummata,  which  may  be  single  or  multiple;  occasionally,  a  fibrosis  of 
the  organ  occurs  attributable  to  syphilis. 

Tuberculosis  of  the  suprarenals  is  probably  the  most  frequent  disease 
to  which  the  organs  are  liable.  In  general  miliary  tuberculosis  the 
adrenal,  in  common  with  other  organs  of  the  body,  is  usually  affected. 
The  most  frequent  lesion  of  the  adrenal,  however,  is  the  chronic  fibro- 
caseous  form  of  tuberculosis.  The  condition  may  be  primary,  but  in  a 
large  percentage  of  cases  is  secondary.  The  tuberculous  deposit  usually 
begins  in  the  medullary  portion  as  scattered  tubercles,  which,  by  coalesc- 
ing, convert  the  organ  into  a  more  or  less  caseous  mass  with  a  notable 
increase  in  the  fibrous  tissue  or,  not  infrequently,  extensive  calcareous 
infiltration.  The  tuberculosis  may  extend  from  the  gland  proper  to 
the  surrounding  tissues.  Elsasser-  found  that  in  eighty-nine  per  cent, 
of  the  cases  of  suprarenal  tuberculosis  both  organs  were  affected. 

Tumors  of  the  Suprarenals.^ — The  most  frequent  tumor  connected 
with  these  organs  is  the  hypernephroma  described  on  page  662.  It  is 
usually  stated  that  the  most  common  neoplasm  of  the  suprarenals  is  the 
adenoma;  it  is  probable  that  some  of  these  gland-like  neoplasms  have 
been  confused  with  the  hypernephroma.  Adenomata  are  occasionally 
more  or  less  diffuse,  consisting  of  irregularly  outlined  nodules  in  the  gland 
tissue;  in  other  instances  the  tumor  is  sharply  circumscribed,  and  some- 
times encapsulated.  Virchow  described  a  form  of  adenoma  that  he 
termed  struma  lipomatosa  suprarenalis.  Such  tumors  simulate  in 
structure  the  cortex  of  the  organ.  Cancer  of  the  suprarenal  may  be 
primary  or  secondary.  Adult  connective-tissue  neoplasms  are  ex- 
tremely rare.  Sarcoma,  both  primary  and  secondary,  occurs,  but  is  far 
less  frequent  than  cancer.  The  cysts  observed  in  the  suprarenals  may 
result  from  hemorrhage  into  the  gland  substance  or  degenerative  changes 
in  adenomata.  Hydatid  cysts  in  the  substance  of  the  glands  are  occa- 
sionally observed. 

Addison's  Disease.^ — Associated  with  tuberculosis,   atrophy,  simple 

^  "Arch.  Gen.  de  Med.,"  1904,  No.  i. 

'  "Arbeit,  a.  d.  Path.  Inst.  Tubingen,"  1904,  Bd.  5,  H.  i. 

^  See  WooUey,  "Amer.  Jour,  of  Med.  Sci.,"  Jan.,  1903;   bibhography. 

*  Vincelet,  These  de  Paris,  1902,  No.  570.  Wiesel,  "Mlinch.  med.  Woch.," 
Oct  13,  1903.  Sinimonds,  "Virchow's  Arch.,"  1903,  Bd.  172,  H.  3,  p.  480.  Abe- 
lous,  "C.  R.  Soc.  de  Biol.,"  1904,  p.  952.  Munch- Petersen,  "  Hospitalstidende," 
vol.  xlvi,  No.  50.     Withington,  "Med.  News,"  Sept.  24,  1904,  p.  591. 


DUCTLKSS   i;i.AN-I)S.  -S7 

or  inrtaniinatory,  neoplasms,  or  heinorrIiai(c  into  the  suprartMials,  tlierc 
occurs  a  series  of  cliniial  phenomena  to  vvhiili  lias  been  applied  the  name 
Addison's  disease.  Tuberculosis  of  the  suprarenal  bodies  is  the  lesion 
most  frequently  found  (about  75  per  cent,  of  the  cases).  Of  the  210 
cases  collated  by  V^incelet,  an  associated  pulmonary  tuberculosis  was 
present  in  122;  other  organs  were  often  involved.  In  addition  to  the 
change  observed  in  the  adrenal  glands,  a  bronzing  of  the  skin  occurs,  due 
to  a  deposit  of  pigment  in  the  Malpighian  layer.  The  cutaneous  pig- 
mentation is  not  uniformly  distributed,  but  is  usually  most  marked  on 
the  exposed  parts.  A  similar  coloration  of  the  buccal  mucosa  may  be 
present,  and  pigmented  areas  occur  on  the  tongue.  The  nervous, 
muscular,  and  cardiovascular  phenomena  are  not  accounted  for  bv  the 
morbid  anatomy.  The  disease  is  sometimes  observed  without  demon- 
strable lesion  of  the  suprarenal  bodies.  Of  281  cases  examined  by 
Lewin,  twenty  per  cent,  showed  no  lesion  of  these  organs.  It  is  usually 
held  that  the  phenomena  are  caused  by  a  suprarenal  inadequacy. 
Abelous  has  shown  that  in  twenty-four  hours  following  the  removal 
of  the  suprarenals  of  the  frog  the  skin  becomes  much  darker.  The  color 
is  restored  by  injecting  o.i  mgm.  to  0.2  mgm.of  adrenalin  into  the  lymph- 
sac;  the  restoration  requires  about  eight  hours  for  its  full  development. 


CHAPTER  XIV. 
THE  VOLUNTARY  MUSCLES. 

A  normal  voluntary  muscle  is  formed  of  fibers  held  together  by  the 
endomysiimi;  these,  collected  in  larger  groups,  are  surrounded  by  the 
perimysium,  and  in  many  localities  the  muscle  is  partly  retained  within  a 
distinct  sheath  called  the  epimysiimt.  The  libers  forming  the  muscle 
vary  in  length,  rarely  exceeding,  however,  from  3  to  5  cm.,  and  measur- 
ing from  10  !>■  to  50  /J!  in  width.  Each  muscle-fiber  is  composed  of  a 
contractile  substance  with  peripherally  placed  nuclei,  and  surrounded  by 
a  sheath  called  the  sarcolemma.  The  various  views  with  regard  to  the 
ultimate  structure  of  the  fibers  will  be  found  in  works  on  histology  and 
do  not  especially  interest  the  pathologist. 

Many  malformations  and  slight  alterations  in  the  origin,  course,  and 
insertion  of  muscles  occur.  These,  however,  are  of  anatomic  rather  than 
of  pathologic  interest. 

Atrophy  of  muscle^  is  observed  under  a  number  of  conditions.  Persis- 
tent pressure  rapidly  leads  to  disappearance  of  the  contractile  substance, 
with  more  or  less  substitution  of  fibrous  tissue.  A  muscle  not  performing 
any  function  usually  shows  progressive  wasting,  constituting  atrophy 
from  disuse;  such  atrophies  are  intensified  by  associated  pressure,  as 
is  seen  when  a  fractured  bone  demands  absolute  rest  and,  at  the  same 
time,  is  subjected  to  the  pressure  of  retentive  dressings.  Fixation  of  a 
joint  (ankylosis),  section  of  a  tendon  or  muscle,  and  causes  removing  the 
force  that  induces  normal  muscular  tension  may  also  bring  about  atrophy. 
Interference  with  innervation,  particularly  the  removal  of  motor  stimu- 
lation as  a  result  of  diseases  of  the  motor  neurons  or  axons,  may  also 
bring  about  atrophy.  Such  atrophies  are  typified  in  the  spinal  and  bul- 
bar lesions  of  the  central  nervous  system.  As  the  disease  usually  begins 
in  certain  muscles,  depending,  of  course,  upon  the  location  of  the  central 
lesion,  and  gradually  progresses  with  the  changes  in  the  central  nervous 
system,  the  term  progressive  spinal  amyotrophy  has  been  applied.  (See 
Diseases  of  the  Nervous  System.)  In  the  disease  called  polioniyelitis, 
particularly  frequent  in  childhood,  there  occurs  an  acute  inflammatory 
lesion  involving  the  motor  cells  in  the  anterior  horns  of  the  spinal  cord, 
with  subsequent  degenerative  changes  in  these  structures ;  as  a  result  of  the 
lesion  in  the  cord,  paralysis,  followed  by  atrophic  processes,  involves  the 
muscles  controlled  by  the  affected  neurons,  constituting  a  condition  called 
infantile  paralysis.  (See  Diseases  of  the  Nervous  System .)  In  other  cases 
the  atrophic  process  is  unassociated  with  recognizable  lesions  of  the 
central  nervous  system  or  peripheral  nerve ;  in  such  instances  the  wast- 
ing is  presumed  to  be  essentially  a  disease  of  the  muscle,  and  the  term 
primary  myopathy  is  applied.     Certain  of  these  atrophies  closely  resemble 

'  Babinski,  "Soc.  Neurolog.,"  Dec.  i,  1904;  "La  Presse  Med.,"  Dec.  7,  1904, 
p.  784. 


TUF-  VOLUNTARY  MUSCLKS.  7S9 

the   proi^'ressive   sjtinal    fonn,   and   tlirx-   have  been  grouped   under  the 
head  of  progressive  muscular  dystrophy. 

Pseudohypertrophic  muscular  paralysis'  (myosclerosis)  is  a  disease 
most  Irefiucnt  m  inaU'  i  hiMri-n,  althoui^h  occasionally  it  is  seen  in  girls; 
two  or  more  memhers  (.)t  the  same  family  are  frcfiuently  attacked. 
Usually,  the  first  indications  of  the  disease  are  observed  in  the  muscles 
of  the  calves,  which  show  considerable  enlargement;  this  may  be 
associateil  with  corresponding  increase  in  the  volume  of  the  anterior 
tibials.  The  marked  enlargement  commonly  occurs  in  the  gluteus 
maximus,  and  usually,  although  to  a  lesser  degree,  in  the  extensors  of  the 
thigh.  The  prominence  of  these  muscles  gives  the  appearance  of  hy- 
pertrophv.  and  hence  the  name.  As  the  increase  in  size  is  associated 
with  deficient  contractile  power  (lessened  function),  the  term  pseudo- 
hypertrophv  is  appropriately  applied.  Associated  with  the  increase  in 
tiie  size  of  the  muscles  indicated,  others  may  show  an  early  wasting — as, 
for   example,   the   flexors   of 

the   knee  and  thigh.     In  the  ^^    •-:    ..^ 

upper  extremities  the  deltoid, 

supraspinatus,  infraspinatus.  " 

and  triceps  are  enlarged,  while  ^  ; 

the  biceps  may  be  atrophied.  ' '  ^ 

Histologically,  during  the 
stage  of  enlargement  the  mus- 
cle-hbers    occasionally    show  ;; 

but  slight  alteration ;  there  is,  ..; 

however,  an  enonnous  in- 
crease in  the  amount  of  fat 
between  the  fibers,  to  the 
presence  of  which  the  appear- 
ance of    hvpertrOphv    is    due.      Hc.  jSs-SEC-noNTAKKs  .  >  .vsTRorNKUius  MrscLK 

7r,  T>-  o^  1  "t?-  of  aChILDSUFFERI.N..   IK.,M    l'>tLl>.)HVPF.RTROPlIIC  -MUS- 

(bee    rig.    380,    also    rig.    134,  cular  paralysis;  Kixkp  in  Fi.emmino's  S«ilution   asu 

p.  227.)  As  a  rule,  the  trans-  g*^';^ Ha,^.)"^"^""'"'"'' ^"''''  '^""''    ^^•*°'"'" ''"' 

verse      measurement      of       the  ,,    Muscle-fibcrs.     b.  Fibrous  and  fatty  ti.ssue.     c.  Blood-vessel 

miicnlp   Hbpr       i.;      dimini'ihpd  'he  lumen  of  whith  has  Ikih  occluded  by  fibrous  Ussue. 

mUSCie-nOer        is      aiminisneu.  xhe  disarranKtment  c.f  the  muscU- fiUrs  and  the  mo-casc 

although     OCCasionallv     fibers  in  the  tibrous  and  fatty  tissues  are  will  shown. 

of  unusual  size  are  en- 
countered. Later,  there  is  a  marked  increase  in  the  amount  of  fibrous 
tissue  without  corresponding  continued  overgrowth  of  the  fat.  The 
muscle-hbers  become  thin  and  irregular.  The  striation.  at  first  nearly 
normal,  rapidlv  grows  less  conspicuous,  and  eventually  disajipears. 
Fat  has  been  observed  within  the  sarcolemma.  which,  a.ssociated  with 
the  granular  changes  in  the  fibers,  would  indicate  that  the  process  is 
essentiallv  a  degeneration.  The  alterations  in  the  contractile  substance 
are  not  uniform  and  do  not  implicate  at  one  time  all  the  fibers  in  a  given 
muscle,  nor  are  all  the  hbers  in  one  area  simultaneously  involveil;  it  is, 
therefore,  patchv,  diffused,  or  irregular  in  distribution.  Late  in  the 
process,  when  the  false  hvpertrophy  has  disappearerl.  the  fragmentation, 
degeneration,  and  ab.sorption  of  the  true  sarcous  elements  are  most 
marked.  . 

A  form  of  muscular  atrophy  occurs  unassociated  with  the  preliminary 

'  Gowers.  "Lancet.  "  April   12.  1002:    also  "Brit.  Med.  Jovir.    "  July  12.  tqo2. 
\K  S9.     Eshner,    "Phila.  Mol.  Jour,"  June  7.  1002. 


,C:5  -^  •-^->«t?ri- 


790 


SPECIAL  PATHOLOGY. 


stage  of  pseudohypertrophy,  and  appearing  more  frequently  in  young 
adults  than  in  children.  Two  types  of  the  lesion  have  been  described — 
(i)  one  by  Erb  and  (2)  one  by  Landouzy  and  D^jerine.  As  to  the 
relation   of   the   two   forms,    opinions   dififer;    some   maintaining   their 

identity,  and  others  holding  that 
thev  are  distinct  processes. 
While  to  a  certain  extent  differ- 
ent muscular  systems  are  in- 
volved, the  lesions  in  the  affected 
muscles  are  not  unlike.  In  the 
form  described  by  Landouzy  and 
D6jerine  the  wasting  begins  in 
the  face,  and  next  involves  the 
muscles  of  the  shoulders  and 
arms.  This  peculiarity  has  led 
to  its  being  called  the  facio- 
scaptdohumeral  type.  In  that 
form  of  muscular  dystrophy  de- 
scribed by  Erb  the  face  is  not 
affected.  ^  The  pectoral  muscles, 
trapezius,  latissimus  dorsi,  bi- 
ceps, triceps,  brachialis  anticus, 
and  supinator  longus,  and  later 
the  muscles  of  the  lower  extrem- 
ity, are  involved.  On  section, 
the  mtiscles  may  have  lost  their 
normal  color,  and  are  largely 
composed  of  fibrous  and  fatty 
tissue.  The  remaining  muscle- 
fibers  are  small;  at  first  striation 
is  retained,  but  later  it  disap- 
pears. It  is  usually  held  that  the 
initial  changes  are  in  the  muscle- 
fibers  and  that  the  increase  of 
connective  tissue  is  secondary. 
In  many  cases,  however,  the  re- 
verse seems  to  be  true.  No 
secondary  lesion  in  the  cord  or 
gangha  has  been  recognized. 

True  hypertrophy  of  muscle 
is   usually    dependent   upon    an 
increased'  demand  for  work  ac- 
companied   by   sufficient    nutri- 
tion.  It  is  most  highly  developed 
in    athletes,    where    systematic 
training  has  brought  the  muscles 
to  the  highest    degree  of  func- 
tional power.     Occasionally,  the 
hypertrophy  may  be  restricted 
to  certain  groups  of  muscles,  and  may,  in  these  cases,  be  dependent  upon 
some  special  work  thrown  upon  them,  as  is  seen  in  the  muscles  of  toe- 
dancers  and  in  artisans  in  whom  certain  groups  of  muscles  are  brought 


Fio.  386. — Progressive  Muscular  Dystkuphv,  Eru 
Type.  (From  "Pennsylvania  Medical  Journal," 
March  1898;  report  by  Dr.  Theodore  Diller,  to 
whom  the  author  is  indebted  for  the  Olustration.) 

The  atrophy  of  the  muscles  forming  the  shoulder  girdle, 
the  pelvic  girdle,  and  the  arms  and  thighs  is  well 
shown.  -N'otice  the  marked  lordosis.  The  muscles 
of  the  forearm  and  cah'cs  are  not  involved. 


TIIK    VOLUNTARY    MUSCLES.  7g  I 

particularly  into  j'lay.  A  certain  amount  of  muscular  hypertrophy 
is  also  observed  in  Thomsen's  disease  {congenital  myotonia). 

A  typical  example  of  hypertrophy  resulting  from  increased  work 
is  seen  in  valvular  disease  of  the  heart.     (See  p.  512.) 

Hemorrhage  into  the  muscles  or  hematoma  of  muscle  results  from 
injury,  either  direct,  as  in  hruisini,'  or  wounds,  or  Irom  tears  in  the  muscle 
due  to  violent  ccjntraction,  as  m  tetanus.  In  typhoid'  and  other  infec- 
tious diseases  rupture  sometimes  occurs  from  slight  muscular  exertion. 
The  sternocleidomastoid  muscle  is  occasionally  ruptured  during  the  de- 
livery of  a  child.  The  interstitial  hemorrhage  and  laceration  of  fibers 
are  sometimes  followed  by  cicatricial  thickening  and  subsequent  con- 
traction; usually,  however,  the  blood  is  absorbed  without  permanent 
alterations  in  the  muscle.  Muscle  ruptures  occurring  in  delivery  of 
the  infant  frequently  give  rise  to  permanent  disability  and  constitute 
an  important  cause  of  congenital  wry-neck. - 

Of  the  infiltrations  occurring  to  muscles,  piii^nunitation  is  deserving 
of  mention  as  being  fre(|uently  associated  with  various  atrophic  processes. 
The  inhltration  is  also  observed  in  old  inflammator\-  areas  and  in  the 
neighborhood  of  chronic  infectious  processes.  Fatty  infiltration  of  muscle 
is  seen  in  obesity,  in  the  overfed,  and  sometimes  in  alcoholics;  occasion- 
ally it  is  localized  to  certain  groups  of  muscles,  in  which  case  the  deposit 
may  be  sufficient  to  justify  calling  the  condition  diffuse  lipoma''  of  muscle. 
Occasionally,  acute  inflammatory  lesions  of  the  muscles  is  followed  by 
the  deposit  of  considerable  calcareous  material.  Amyloid  infiltration 
is  rare;  it  is  occasionally  observed  in  the  neighborhood  of  inflammatory 
processes,  and  at  times  is  seen  independent  of  existing  inflammation. 
The  muscles  of  the  tongue  and  larynx  are  said  to  show  the  changes  most 
frequently.     The  deposit  is  between  the  fibers. 

Degenerations. — Of  the  various  degenerative  changes  in  muscles. 
cloiiJy  si^rllini:,  and  fatty  degeneration  are  most  common.  The  alterations 
seen  in  the  fibers  are  not  different  from  those  already  described  in  the 
heart  muscle.  (See  pp.  242,  243,  and  491.)  In  edema  vacuolization  or 
hydropic  degeneration  of  the  fibers  occurs.  It  is  usually  manifested  by 
the  appearance  of  vacuoles  within  the  fibers.  These  vacuoles  are  some- 
times numerous  and  small,  and  in  other  instances  they  are  large  and 
single.  (See  p.  245.)  Distinct  separation  of  the  contractile  substances 
(fragmentation)  frequently  follows  degenerative  changes,  and  an  inter- 
stitial fibrosis  is  also  occasionally  present.  Hyaline  degeneration  (p. 
247).  accompanied  or  preceded  by  coagulation  necrosis  (p.  251)  of  the 
muscle-fibers,  is  observed  in  the  course  of  infective  di.seases — con- 
spicuous among  which  may  be  mentioned  typhoid  fever,  in  which  disease 
the  abdominal  muscles  most  frequently  show  the  change. 

Myositis  or  inflammation  of  muscle  results  from  a  number  of  causes 
and  occurs  in  several  forms:  wounds,  tears,  and  hemorrhages  into  the 
interstices  of  muscle  are  attended  by  an  inflammation  which,  in  the 
absence  of  infection,  is  usually  slight  and  terminates  in  repair,  (iowers* 
believes  that  lumbago  and  certain  forms  of  muscular  rheumatism,  stiff 

'  Porochaud.  "Gaz  Med.  de  N'antes."  i<>04.  No.  38,  and  Ferochaud  and  Don- 
cet,  "Gaz.  Med.  de  Nantes."  Sept.  17.  1904. 

'  Maass.  "Zeit.  f.  Orthopadische  Chirurpie."  100.^.  xi,  p    416. 
'  Debuck  and  L'Moor,  "  Beljiique  Med."  Nov..  1900. 
*   '  Brit    Med.  jour.  '  Jan.  16,  1904,  p.  117. 


792 


SPECIAL  PATHOLOGY. 


neck  and  pleurodynia,  are  inflammatory  conditions  aft'ecting  the  inter- 
stitial structure  of  muscle,  for  which  condition  he  proposes  the  name 
fibrositis. 

Acute  myositis  may  be  simple  or  suppurative ;  there  is  also  a  form  in 
which  a  number  of  muscles  are  involved,  called  polymyositis.  In 
hemorrhagic  myositis  the  inflammation  is  accompanied  by  hemorrhages 
into  the  afl:ected  muscles.  In  acute  nonsuppurative  myositis,  or  simple 
myositis,  the  muscle  is  swollen,  tender,  commonly  rigid,  on  section  dark 
and  may  contain  areas  of  hemorrhages.  Microscopic  examination  shows 
the  muscle-fibers  swollen  and  often  necrotic  and  fragmented ;  edema  and, 

in  acute  cases,  fibrin  are  present 
in  the  interstitial  tissue  which 
is  also  infiltrated  by  varying 
numbers  of  mononuclear  leuko- 
cytes. 

Acute  suppurative  myositis 
results  from  direct  infection,  as 
by  wounds,  or  propagated  sup- 
purative lesions  contiguous  to 
the  muscle,  rarely  by  lympho- 
genous extension  and  occasion- 
allv  the  bacteria  are  deposited 
from  the  blood.  Hematogenous 
infections  of  the  muscles  are 
commonly  associated  with  some 
form  of  infection  in  which  bac- 
teria are  expected  to  enter  the 
circulation.  The  condition  has 
been  observed  in  typhoid,  al- 
though in  most  instances  ty- 
phoidal  myositis  stops  short  of 


\.. 


-?^. 


^;^ 


Fig.  387. — Interc»stai,  Muscle,  Accte,  Nonsuppura- 
Ti\'E,  Interstitial  Myositis. 

Transverse  section,  from  a  case  of  epipneumonic  pleurisy, 
showing  dissociation  of  fibers,  interfascicular  leukocytic 
infiltration,  and  slight  fibrin  formation.  Tissue  fixed 
in  Zenker's  fluid;  hematoxylin  and  eosin  stain. 

A,  A,  A.  Granular  and  fragmented  muscle-fibers.  B. 
Accumulation  of  leukocytes  and  fibrin  aroimd,  and  ex- 
tending between  the  muscle-fibers.  In  some  areasthe 
change  is  more  marked  than  in  others,  and  at  points 
many  polymorphonuclear  leukocytes  can  be  seen. 


suppuration;  in  Scannell's^  case 
the  rectus  abdominis  muscle  was 
involved  and  the  condition  was 
mistaken  for  appendicitis.  Sup- 
purative polymyositis  usually 
accompanies  pyemia,  septicemia, 
and  other  forms  of  bacteremia; 
it  has-been  observed  in  gonor- 
rhea.^ The  myositis  infectiosa, 
especially  frequent  in  Japan,  be- 
longs with  this  group;  of  the 
thirty-four  cases  recorded  by  Miyake,^  all  but  one  terminated  in  suppura- 
tion ;  cultures  disclosed  the  Staphylococcus  aureus  in  thirty-three  of  the 
patients ;  in  one  case  the  lesions  were  due  to  the  streptococcus.  The  alter- 
ations in  the  muscle,  constituting  a  conspicuous  part  of  Lud wig's  angina 
(p.  679),  are  manifestations  of  an  acute  diffuse  interstitial  suppurative 
myositis  with  secondar}'  degenerative  and  necrotic  changes  in  the  muscle- 

'  "Boston  Med.  and  Surg.  Jour.,"  Nov.  26,  1903. 

=>  Harris  and   Haskell,    "Johns   Hopkins   Hosp.  Bull,"   Dec,    1904.      Bisquet 
and  Bichelonne,  "Revue  de  Med.,"  May  10.  1904. 

'  "Mitth.  a.  d.  Grenzgebiet.  d.  Med',  u.  Chir.,"  1904.  Bd.  xiii,  p.  155. 


TlIK  VOLUNTARY   MUSCLES. 


793 


fibers.  The  same  lesion  may  result  from  similar  infections  due  to  other 
causes.  In  such  conditions  the  interstitial  tissue  contains  varying  num- 
bers of  polymorphonuclear  leuk«jcytes,  serum,  and  librin,  and  rlestructive 
lesions  of  the  musclc-tihcrs  are  constantly  present;  the  last  are  essen- 
tial! v  lUH  rotic.  Localized  or  circumscribed  suppurative  myositis,  or 
muscle  abscess,  docs  not  ditVfr  (.■sscniiall)'  troin  oiIut  aliscfsst-s,  altliouj^h 
sometimes  it  extends  with  great  rapidity.  It. may  result  from  infec- 
tion primary  in  the  tendon-sheaths  or  extension  from  jKira-articular 
suppuration. 

Acute  polymyositis,  also  called  dermatomyositis,'  or,  when  the  mucosae 
are  also  afYected,  dermato-mucoso-myositis,  is  probably  an  infection, 
although  Steiner  concludes  that  the  cause  remains  undetermined.  This 
observer  has  been  able  to  collect  twenty-eight  cases,  three  of  which 


Fig.  388. — Myositis,  Acute  Diftdse  Suppurative.    Case  of  Lcdwio's  .\nci.va. 

A.  Fragmenting  muscle-fiber.      B.  Same  containing  myoclasts.      C.  Vcssil  with  swollen  endothelium.     D.   D. 

Pneumococci  to  which  the  process  was  due. 

occurred  in  the  United  States.  Any  or  all  the  muscles  may  be  involved ; 
they  are  swollen,  red  or  pale  yellow,  sometimes  streaked  with  gray  or 
reddish  striae,  and  in  consistency  may  be  tinn.  or  soft  and  boggy ;  hemor- 
rhages are  occasionally  present.  Histologically  the  fibers  are  granular, 
hyaline,  sometimes  fragmented,  and  occasionally  fattv.  Interstitial 
swelling  and  Ivmphoid  accumulations  occur;  the  spleen  is  soft  and  en- 
larged and  bronchopneumonia  is  sometimes  present.  Subcutaneous 
edema  and  cuticular  inflammatory  changes  are  conspicuous  clinical 
features  of  the  affection.  Stomatitis,  with  or  without  ulceration,  and 
angina  have  been  observed.  In  some  cases  the  condition  is  accom- 
panied by  polyneuritis. 

'  Steiner.  "Jour,  of  E.xner.  Med.."  1905,  vol.  vi,  p.  407-     Strong,  "  Deut.  Zeit. 
f.  klin.  Med,"  1Q04,  Bd.  Hit.     Bauer.  -Munch,  med.  Woch.."  Jan.  36.  1904.  No.  4- 


794 


SPECIAL  PATHOLOGY. 


Parasitic  myositis  is  a  local  lesion  resulting  from  the  deposit  of  animal 
parasites  in  the  muscle;  in  trichinosis  (p.  204)  it  is  a  polymyositis  and  is 
usually  accora])anied  by  eosinophilia  (p.  417). 

Chronic  interstitial  myositis/  also  called  fibrous  myositis,  sclerosing 
myositis,  myositis  fibrosa,  and  myositis  ivith  contraction,  is  a  protracted 
inflammation  of  muscle  attended  by  the  formation  of  fibrous  tissue  and 
progressive  atrophy  of  the  fibers  of  the  affected  tissues.  The  condition 
may  be  primary,  in  which  case  it  is  called  idiopathic,  or,  when  due  to 

trauma,  ischemia,  or  persistent  local 
V  irritation,  the  lesion  is  spoken  of  as 

secondary  interstitial  myositis.  Little 
is  known  concerning  the  changes  oc- 
curring in  the  muscles  in  the  so-called 
chronic  muscular  rheumatism,  but  in 
some  instances  the  structural  altera- 
tions represent  mild  grades  of  this  pro- 
ductive interstitial  myositis;  the  fi- 
brosis is  rarely,  if  ever,  marked  in 
rheumatic  cases.  When  myositis 
fibrosa  is  progressive,  the  affected 
muscles  waste,  become  firmer  and  con- 
tracted, distorting  the  limb,  and  fixing 
the  joints,  which  later  may  ankylose. 
Batten  has  shown  that  granular  and 
fatty  degenerations  affect  the  muscle 
fibers  in  direct  proportion  to  the  ex- 
tent of  the  fibrosis.  In  some  cases 
the  fibrous  tissue  is  deposited  in 
islands,  justifying  the  name  insular 
or  nodular  fibrous  myositis.  The  con- 
dition has  been  mistaken  for  neo- 
plastic formation,  and  in  one  case  the 
scapula  was  excised  under  the  convic- 
tion that  the  process  was  sarcomatous. 
The  enlargement  of  the  muscles  seen 
in  the  early  stages,  before  degenera- 
tive changes  occur  in  the  fibers,  is 
often  confusing.  At  this  time  the 
microscope  shows  an  irregular  and 
rarely  abundant  infiltration  by  mon- 
onuclear leukocytes;  later  these  cells 
are  inconspicuous  or  absent  and  the 
interfibrillary  deposit  is  almost  exclu-, 
sivelv  fibrous  tissue,  which,  in  some 
cases  contains  considerable  fat.  Asso- 
ciated obliteration  of  the  vessels  is  often  found  and  is  probably  the  cause 
of  some  cases. 

Under  the  name  chronic  ossifying  myositis  (myositis  ossificans)  has 

^  Biggs,  "'Univ.  of  Penna.  Med.  Bull.,"  Dec,  1901.  Batten,  "Clin.  Soc.  of 
London,"  Nov.  13.  1903;  "Lancet,"  Nov.  21,  1903.  Pemlce,  "  Rif .  Med.,"  Oct. 
ig,  1904,  No.  42.  Coplin,  "Path.  Soc.  of  Phila.."  Jan.  28,  1904;  "Amer.  Jour,  of 
Med.  Sci,"  May,  1904. 


'^^ 


'-mt^ 


Fig.  389. 


-Intercostal  Muscle. 

Transverse  section,  from  a  case  of  suppurative 
pleurisy  of  several  months'  duration,  showing 
advanced  fibrosis  and  lipomatous  change. 
Tissue  fixed  in  Zenker's  fluid;  hematoxylin 
and  eosin  stain. 

A.  One  of  several  granular  fibers,  some  of  which 
are  fragmented  and  undergoing  absorption. 
B.  A  small  group  of  greatly  shrunken  muscle- 
fibers.  C.  Relatively  large  mononuclear  cell, 
not  very  abundant,  but  commonly  associated 
with  fibroblastic  elements.  D.  The  leader 
from  this  letter  passes  between  two  imper- 
fectly presented  fat  bodies,  a  number  of  which 
are  present  in  the  newly  forming  or  formed 
fibrous  tissue.  The  fat  content  is  scanty  in 
the  particular  field  from  which  this  drawing 
was  made. 


THK   VOLUNTARY    MUSCLES. 


79  5 


been  described  an  allection  the  inllanimatory  character  <>i  which  has  been 
indisputably  estabUshed.  The  inflammation  is  associated  with  the  pro- 
duction of  calcareous  deposits  between,  in,  or  near  the  muscles.  The 
fact  that  the  muscle-tibers  show  but  little  alteration,  even  late  in  the  pro- 
cess, indicates  that  the  disease  essentially  involves  the  connective  tissue. 
In  some  cases  the  bony  deposit  follows  injury,  particularly  sli^dit  repeated 
bruisintjs;  in  other  instances  no  history  of  trauma  can  be  elicited.  There 
is  usuailv  proliferation  of  the  connective  tissue  of  the  muscle,  which  pro- 
gresses to  the  formation  of  bone,  very  much  as  is  observed  in  similar  proh- 
ferative  processes  affecting  the  periosteum.  xVs  the  structural  changes  are 
not  restricted  to  the  muscle,  but  occur  also  in  the  fasciae  and  tendons,  all 
sorts  of  irregular  osseous  or  osteoid  collections  can  be  produced.  The 
disease  pursues  a  chronic  course,  usually  beginning  in  the  muscles  of  the 


-H 


Fic.  30O. — OsstrviNC  Myositis.    A.  Matrix  of  osteoid  tissue.     B.  H,  Fragmenting  muscle-fibers 


neck  or  back,  to  which  it  may  remain  restricted.  Later,  it  sometimes 
manifests  a  tendency  to  {)rogress  and  involves  all  the  muscles  of  the  trunk, 
with  ankylosis  of  joints,  rendering  the  limbs  and  trunk  stiff,  or  even- 
tually entirely  rigid.  The  bony  collections  are  irregular,  consisting  of 
flake's  and  spicules,  which  later  often  coalesce  and  form  larger  masses. 
Various  theories'  intended  to  explain  the  condition  have  been  advanced. 
The  new  bone  has  been  attributed  to  ectopic  periosteum,  congenitally 
out  of  place  or  detached  by  muscle  contraction  or  trauma ;  some  believe 
the  affection  is  a  deflnite  dystrophy  alHed  to  pseudohypertrophic  muscu- 

'  Taylor.  'Annals  of  Surgen,"."  June.  1903.  Rt-nzi.  -Gaz.  deRli  Ospedali  ed 
delle  Clin.,"  Sej>t.  20.  1903.  p.  I'lS;'  Busse  and  Hlccher,  "Dent  Zeit.  f.  Chir.." 
June.  1904.  Bd.  73.  Cahier.  "  Revue  de  Chir."  June.  ioo.j.  v  Sj;.  Combv  and 
"Davel.  "Arch,  de  mM.  des  enfants,"  Paris,  July,  190  j 


796  SPECIAL  PATHOLOGY. 

lar  atrophy.  It  has  been  regarded  as  neoplastic,  and  the  resemblance 
to  tumor  formation  is  often  striking;  I  have  known  two  instances  in 
which  extremities  were  amputated  under  conviction  that  the  enlargements 
were  ossifying  sarcomata.  The  histology  is  often  confusing;  the  affected 
areas  are  infiltrated  by  mononuclear  cells  which  strongly  resemble  those 
of  sarcoma.  Giant  cells,  apparently  identical  with  such  structures 
occurring  in  the  marrow,  are  frequently  present.  Bone  formation  by 
the  evolution  of  an  osteoid  tissue  without  the  production  of  cartilage  is 
the  usual  order  followed;  in  some  cases,  however,  cartilage  is  present. 
There  is  usually  a  cellular  matrix  containing  fragmenting  and  degenerat- 
ing muscle-fibers  which  later  disappear.  The  osteoid  tissue  consists  of 
granular  substance  in  which  calcification  rather  than  true  bone  forma- 
tion first  takes  place ;  later   imperfect  Haversian  systems  and  more  or 

less    typical    bone  are 
produced. 

Tuberculosis  of 
muscle^  is  exceedingly 
rare;  of  all  the  tissues 
in  the  body,  muscle 
seems  most  resistant  to 
invasion  and  coloniza- 
tion by  the  tubercle 
bacillus,  and  often  es- 
capes virulent  and 
wide-spread  infection 
such  as  is  observed  in 
disseminated  acute 
miliary  lesions.  There 
is  little  reason  for  be- 
lieving that  primary 
tuberculosis  of  a  pre- 
viously healthy  muscle 
ever  occurs.  Secondary 
tuberculosis  is  usually 
due  to  direct  extension 
from  contiguous  le- 
sions. Plantard  recog- 
nizes three  forms  of  muscle  tuberculosis:  (i)  The  tuberculoma,  which  is 
usually  caseous,  but  it  may  contain  a  large  amount  of  fibrous  tissue  and 
resemble  a  gumma.  (2)  Cold  abscess,  which  is  really  a  more  diffuse  form 
of  caseous  tuberculosis  of  muscle,  and  is  generally  due  to  extension  of 
osseous  tuberculosis,  arising  in  the  bone  to  which  the  muscle  or  its  sheath 
is  attached.  (3)  Tuberculous  interstitial  fibroid  myositis  arising  in  muscles 
contiguous  to  tuberculous  lesions  and  probably  due  to  local  dissemination 
of  poisons  produced  in  adjacent  structures;  this  is  the  lesion  observed 
in  muscles  lying  next  to  tuberculous  joints,  glands,  or  bones.  In  ad- 
dition to  the  foregoing  should  be  mentioned  occasional  instances  of 
definite  miliary  tuberculosis  of  muscle. 

Syphilis  of  muscle^  is  of  infrequent  occurrence.     An  acute  nonsup- 

'  Plantard,  These  de  Paris,  1901.  Lejars,  "La  Sem.  Med.,"  June  i,  1904, 
vol.  xxiv,  No.  22;    "Medical  Press  and  Circular,"  June  22,  1904. 

^  Bigot,  These  de  Toulouse,  1901.  Busse,  "Arch.  f.  klin.  Chir.,"  1903,  vol. 
69,  Nos.  I  and  2.     Fordyce,  "Jour,  of  Cutaneous  Diseases,"  April,  1903. 


Fig.  391. — UbMiviNL.  Myositis. 
A,  A.    Fragmenting  muscle-fibers.     B,  B.    Giant  marrow  cells.     The 
matrix  in  which  A  and  B  are  situated  is  a  granular  partly  calcified 
osteoid  tissue. 


Till-;    Vlil.lNlAK\    ML>CI.I-.>.  ;«;/ 


purative  diffuse  interstitial  myositis  (  Kaonl)  octurs  during  the  secondary 
stage  of  s\i'hilis,aii<l  ii  is  possiMi-  that  tills  forms  the  starting-point  of  a 
more  chronic  tibroid  form,  developing  later  in  the  infection.  In  both 
the  acute  and  chronic  types  of  syphilitic  myositis  the  alterations  in 
the  muscle-hbers  succeed  the  interstitial  changes.  Histologically  the 
affected  muscle  is  first  infiltrated  by  mononuclear  cells  and  later  an 
excess  of  fibrous  tissue  is  produced.  The  most  common  manifestation  of 
muscle  syphilis  is  the  gumma,  which  in  this  structure  does  not  differ  from 
similar  lesions  occurring  elsewhere  (|).    17Q). 

Leprosy  and  actinomycosis  rarely  involve  the  muscles. 

Tumors  of  muscle,  when  primary,  necessarily  belong  to  the  con- 
nective-tissue series.  Lipoma,  which  may  be  circumscribed  or  diffuse, 
occasionally  occurs;  fibroma  and  myxoma  have  been  observed.  Chou- 
dromata  are  exceedingly  rare.  The'  bone  formations  of  myositis  ossi- 
ficans (p.  794)  are,  by  some  observers,  included  with  the  neoplasms 
arising  in  muscle.  Independent  of  such  origin  osteomata  in  this  situation 
are  infrequent.  Aui^ioma^  is  not  an  exceedingly  rare  tumor  and  may 
be  mistaken  for  sarcoma.  It  is  most  frequent  in  the  muscles  of  the  ex- 
tremities and  is  probably  of  traumatic  origin.  As  a  rule,  the  neoplasm 
is  restricted  to  a  single  muscle,  all  of  which  may  be  involved.  Paton 
reports  an  instance  in  which  the  entire  gracilis  muscle  was  affected.  The 
angioma  mav  be  circumscribed  or  diffuse,  simple,  plexiform,  or  cavern- 
ous; the  last  is  the  usual  form.  Thrombosis,  calcification,  and  trans- 
formation into  sarcoma  have  been  observed  in  angiomata  of  muscle. 
Katholitzkv  has  reported  an  instance  of  lymphangioma  of  the  muscles 
of  the  forearm.  Sarcoma  is  probably  the  most  common  primary  tumor 
of  muscle,  in  which  the  neoplasm  often  proves  extremely  malignant. 
Secondary  cancer  and  secotidary  sarconia  are  freriuently  observed  in  the 

muscle. 

Parasites  of  Muscle. -Trichina-  (p.  204),  cysticercus  cfellulosae  (p. 
197 ).  and  hydatids  (p.  199)  invade  the  muscles. 

'  Magarucci.  "11  Policlinico,"  Nov..  1902.  Rigaud.  These  de  Paris,  iqo.^. 
Keeler.  "Deut.  Zeit.  f.  Chir,"  Sept.,  1904,  Bd.  74. 


CHAPTER  XV. 

BONES  AND  JOINTS. 

THE   BONES. 

Normal  Structure. — Histologically,  bone  consists  of  a  modified  form 
of  connective  tissue  presenting  certain  structural  peculiarities  in  dif- 
ferent bones  and  in  different  parts  of  the  same  bone.  The  long  bones, 
except  at  the  articular  ends,  are  covered  by  a  membrane  called  the 
periosteum.  This  structure  consists  of  dense  connective  tissue  which  is 
divided  into  two  distinct  layers.  The  outer  layer  affords  attachment  for 
the  aponeuroses,  tendons,  ligaments,  and  fasciae,  with  which  it  is  practi- 
callv  continuous.  It  is  comparatively  rich  in  blood-vessels,  some  of 
which  pass  to  the  underlying  layer  and  afford  additional  nutrition  to  the 
adjacent  bone.  As  a  result  of  its  intimate  association  with  the  sur- 
rounding tissues,  this  layer  of  the  periosteum  is  subject  to  the  diseases, 
particularly  the  chronic  infective  processes,  involving  the  adjacent 
structures.  It  is  intimately  connected  with  the  underlying  or  genetic 
layer,  from  which  it  can  not  always  be  easily  differentiated,  the  two 
forming  a  fairly  uniform  membrane.  The  outer  layer  is  composed  of 
dense  fibrous  tissue;  the  inner  is  richer  in  elastic  tissue,  and  immediately 
adjacent  to  the  superficial  stratum  of  bone  it  contains,  in  varying  num- 
bers, osteoblastic  elements,  through  the  activity  of  which  the  circum- 
ferential growth  ^  the  bone  is  accomplished.  The  degree  of  adhesion 
between  th^  inner  layer  and  the  bone  proper  varies.  Besides  the  some- 
what loose  cellular  attachment,  the  genetic  la3^er  is  further  secured  in 
manv  localities  by  the  presence  of  certain  fibers  that  penetrate  the 
compact  portion  of  the  bone,  and  also  by  the  vascular  communication 
between  the  two  structures,  through  which,  in  part,  the  nutrition  of 
both  is  maintained. 

Immediatelv  adjacent  to  the  periosteum  is  the  compact  portion  of  the 
bone,  while  still  deeper  the  supporting  osseous  structure  assumes  a 
spongy  consistence,  constituting  the  spongy  layer.  The  quantity  of 
compact  tissue,  as  compared  with  the  spongy,  varies  in  different  bones 
and  is  not  uniform  for  all  parts  of  the  same  bone.  Thus,  in  the  long 
bones  there  is  a  relatively  thick,  compact  layer  in  the  shaft,  while  the 
extremities  are  composed  for  the  most  part  of  spongy  tissue  covered  b}^ 
a  thin  shell  of  compact  bone.  The  circulation  of  fluids  within  the  com- 
pact portion  of  the  bone  is  secured  through  the  presence  of  two  systems  of 
channels — one  of  which  is  formed  by  Volkmann's  canals  and  the  other 
bv  the  Haversian  canals.  The  latter  differ  from  the  former  in  the  fact 
that  each  canal  constitutes  the  center  of  a  lamellar  system.  Around  this 
central  space  are  arranged  successive  plates  of  osseous  ground-substance, 
constituting  the  Haversian  lamellae.  Between  the  latter  are  incomplete 
or  partial  lamellas,  called  the  interstitial  lamellae,  while  at  the  periphery, 
immediately  under  the  periosteum,  are  the  periosteal  or  outer  circum- 
ferential lamellae.     Within  the  various  lamellae  already  mentioned  are 

798 


BONES   AND  JOINTS.  -<,ij 

smaller  canals,  called  the  lacunic.  The  compart  layer  ot  the  bone, 
projected  inward  toward  the  medulla,  divides  the  inner  area  into 
irregular  spaces,  resemblinjj  the  cavities  found  in  a  sponj^e,  and  hence 
this  portion  of  the  hone  is  called  the  sponi^'v  layer.  In  the  meshes  of 
this  sponge-like  tissue  is  held  the  bone-marrow,  which  further  occupies 
the  central  canal  or  cavity  of  bone. 

Bone-marrow. — Macroscopically,  two  kinds  of  marrow  are  recog- 
nized: (i)  A  red  uiarroxv,  composed  of  a  connective-tissue  reticulum 
holding  in  its  meshes  certain  cellular  elements.  (See  Figs.  392  and 
393.)     Conspicuous  among  the  cells  of  the  marrow  are  the  uninucleated 


^     J»«  -iJ®^     #    "■•^'   sii-  (A 


Fig.  392.— Section  of  Bovk-mabrow  or  Rabbit.  Shovvt.nc  the  Delicate  CoNNEcnvE-nssuE  Retict-lcji 

Co.vTAiM.sf;  the  Differe.vt  Ei.kme.nts  of  the  Marrow.     :<  400.— (Sehafer.) 

a,  h.  Heraatoblasts.    6,  g.  Eosinophilous  colls  (Rranulc  cells),    c,  d.  Marrt.w  cells  (plasma  cells),    t.  Connocli^c- 

lissuc  reticulum.     /.  Fat  space,     i.  Giant  cell. 

and  multinucleated  giant  cells.  Some  of  these  cells  attain  a  diameter 
three  or  four  times  that  of  the  polymorphonuclear  leukocyte,  while  cells 
tinctorially  and  structurally  identical,  but  much  smaller  in  size,  are  to  be 
recognized  as  probably  miniature  myeloplaxes.  Leukocytes  are  present 
in  varving  stages  of  development;  if  it  is  assumed  that  the  white  blood- 
cells  are  different  throughout  their  life  history,  then  it  must  be  stated 
that  all  kinds  of  leukocytes  are  found  in  the  i)one-marrow.  (See  Table 
of  Leukocytes,  pp.  414  and  415.)  The  bone-marrow  also  contains  a  cell 
presumed  to  be  the  parent  of  the  erythrocyte— called  the  crythroblast. 
The  latter  is  nucleated;  the  nucleus  possesses  the  usual  affinity  for  basic 
dves,  while  the  cell  cytoplasm  gives,  to  a  varying  extent,  the  tinctorial 


8oO  SPECIAL    PATHOLOGY. 

reaction  of  protoplasm  containing  hemoglobin.  The  amount  of  fat 
present  in  this  type  of  marrow  varies,  but  it  is  usually  not  abundant. 

The  (2)  yclloiv  marron'  is  composed  largely  of  fat,  and  contains  but 
few  of  the  special  cellular  elements  just  described,  and  even  these  are  not 
present  in  many  localities. 

The  nutrition  of  bone  is  secured  through  an  abundant  blood-sup- 
plv  entering  by  means  of  the  vascular  twigs  in  the  periosteum,  to 
which  reference  has  already  been  made,  as  well  as  by  special  nutritive 
branches.  The  vascular  twigs  from  the  periosteum  pass  through  the 
Haversian  and  Yolkmann's  canals,  communicating  with  branches  from 
the  bone-marrow  having  their  origin  in  the  nutritive  vessels  passing 
through  the  compact  portion  of  the  bone  directly  to  the  marrow  tissue. 
During  the  earlier  periods  of  osseous  growth  a  high  degree  of  vascularity 
is  necessarv  for  the  general  nutrition  of  the  bone  as  well  as  for  its  en- 
largement circumferentially  and  axially.  In  long  bones  possessing 
epiphyses  there  is  usually  an  abundant  vascular  network  between 
these  structures  and  the  shaft  properly  so  called.  At  this  Hne  of  junc- 
tion the  veins  afford  communication  between  the  overlving  tissues  and 


fgf\ ,  Hematoblasts. 

— -^^^  {^k^  '     Colored  Blood-corpuscles. 


Giant  Cell. 


Fig.  393. — Elements  of  Hdmak  Bone-marrow.     X  600. 
I  to  5.  Various  forms  of  bone-cells.     6.  Eosinophilous  cell. — (Stohr.) 

the  bone-marrow,  and  hence  infective  or  inflammatory  processes  at- 
tacking these  special  areas  are  extremely  prone  to  involve,  when  arising 
externally,  the  medulla,  and,  when  beginning  in  the  marrow,  can  extend 
through  the  vascular  disc  to  the  para-osteal  structures. 

For  a  description  of  the  process  by  which  bone  is  developed  the 
student  is  referred  to  standard  text -books  on  histology  and  embryology. 
There  is,  however,  one  element  deserving  of  special  consideration,  by 
reason  of  the  fact  that  it  has  important  bearings  on  morbid  processes 
affecting  the  bones,  and,  even  when  pathologic,  usually  closely  resembles 
the  normal  process.  The  condition  to  which  reference  is  made  is  called 
osseous  resorption.  Bone  is  absorbed  through  the  intervention  of  large 
nucleated  masses  of  protoplasm  which  constitute  one  form  of  giant 
cells;  these  bodies  apply  themselves  directly  to  the  calcified  matrix, 
within  which  they  excavate  small  cavities,  called  Howslip's  lacitncB. 
The  particular  cells  accomplishing  this  function  are  called  osteoclasts. 
Conclusive  evidence  as  to  the  method  by  which  they  bring  about  the 
excavation  in  the  calcified  matrix  is  still  wanting.  It  is  reasonable, 
however,  to  assume  that  the  cell  secretes  a  material  which  liquefies  and 
renders  absorbable  the  dense  structure;  the  process  may  therefore  be 
regarded  as  closely  allied  to  certain  forms  of  phagocytosis  (pp.  98  and 


BONES    AND     lOlNTS. 


Soi 


2go).  In  j^rowini^  hone,  while  the  osteotlasts  are  },'radu:illy  leading  to 
osseous  ahsorption  in  the  interior,  the  exterior  is  receiving,'  additional 
bone,  laid  down  by  cells  already  mentioned  as  present  in  the  genetic 
layer  of  the  periosteum,  and  railed  .>v/,  o/i/./v/v  This  form  of  ostcot'encsis 
is  calle<l  osseous  apposition. 


FlC.  304.— ACHONDKOPLASIA. — (CotiU^y,  courtesy  oj  Dr.  HUliJrli 


Malformation  of  Bone.  In  the  osseous  skeleton  many  i^erversions  of 
development  occur.  These  are  usually  manifested  by  defective  or 
perverted  bone  formation,  which  may  be  due  to  reco},mizable  diseases  of 
the  blood-vessels  or  may  arise  without  a  demonstrable  cause.  As  the 
larger  part  of  the  osseous  skeleton  is  preceded  by  a  stage  of  cartilage, 
anv  defect  in  the  laying-down  of  this  priman,'  enehondral  matrix  (achon- 
5^ 


8o2  SPECIAL    PATHOLOGY. 

droplasia)  ^  becomes  manifest  in  the  later  growth  and  development  of  the 
bone.  Aside  from  these  defects  in  the  initial  process  of  osseous  growth, 
there  is  to  be  recognized,  later,  certain  malformations  depending  upon 
failure  in  the  extent  of  growth ;  or  it  would  be  better  to  say  the  formation 
of  the  bone  is  not  completed.  Thus,  arches  may  fail  to  coalesce,  as  is 
observed  in  the  superior  maxilla,  where  developmental  arrest  gives  rise  to 
harehp  (see  p.  673),  cleft  palate,  etc.;  or  in  the  chest,  resulting  in  the 
formation  of  a  fissure  that  may  extend  the  entire  length  of  the  sternum. 
A  posterior  fissural  deficiency  is  sometimes  present  in  the  spinal  column, 
the  lamina  of  the  vertebrae  having  failed  to  complete  the  arch  that 
normally  forms  the  posterior  wall  of  the  spinal  canal,  giving  rise  to  the 
presence  of  a  fissure,  constituting  a  condition  known  as  rhachischisis. 
(See  Malformation  of  the  Central  Nervous  System.) 

Agenesis  may  be  restricted  to  one  bone,  or  even  to  a  part  of  the  bone, 
or  It  may  be  mqre  extensive,  involving  the  osseous  structures  of  a  large 
area.  Sometimes  the  defective  development  is  remarkably  uniform,  all 
the  bones  of  the  skeleton  being  influenced  to  approximately  the  same 
degree,  giving  rise  to  the  typically  symmetric  and  accurately  miniature 
individual  called  the  dwarf — microsomia,  nanosomia  (see  p.  222).  In 
other  cases  the  arrest  in  growth  is  restricted  to  certain  areas  or  to  single 
bones,  leading  to  asymmetry,  one  limb  or  one  part  of  the  pelvis  or  one 
side  of  the  chest  showing  a  development  that  approximates  the  normal 
and  is  far  in  excess  of  that  attained  by  the  opposite  side. 

Of  the  ultimate  cause  of  these  conditions  httle  is  known.  Local 
arrests  may  depend  upon  morbid  processes  influencing  the  nutritive 
organs  during  developmental  stages ;  prominent  among  the  causes  acting 
in  this  way  may  be  mentioned  rickets  and  syphiHs.  The  deformities 
indicated  are  commonly  attributed  to  inheritance,  diseases  of  the  thyroid 
gland,  intrauterine  conditions  including  the  influences  of  heredity  and 
maternal  disease,  and  imperfect  osteogenesis;  it  must  be  evident  that 
such  explanations  are  insufficient  and  unsatisfactory. 

It  is  equallv  difficult  to  explain  the  remarkable  overgrowth  of  bone 
occasionally  observed.  The  fact  that  osseous  overgrowth  is  sometimes 
associated  v/ith  diseases  of  the  hypophysis  cerebri  offers  but  little  aid  in 
our  effort  to  solve  this  obscure  problem.  Knowing  next  to  nothing 
concerning  the  functions  of  the  hypophysis,  it  is  quite  impossible,  for  the 
present  at  least,  to  infer  the  actual  relation  existing  between  morbid 
processes  in  this  organ  and  the  tissue  overgrowth  involving  the  bones 
and  other  tissues.  In  acromegaly  a  more  or  less  uniform  enlargement  of 
many  of  the  bones  of  the  skeleton  occurs.  There  is  true  increase  in 
length  and  circumferential  enlargement  due  to  the  deposit  of  osseous 
matter  in  the  subperiosteal  layers,  either  alone  or  associated  with  osteo- 
phytic  excrescences. 

Changes  in  the  bone-marrow  resulting  from  the  influence  of  systemic 
conditions  and  often  independent  of  local  disease,  properly  so  called, 
are  now  well  known.  Reference  has  been  made  to  structural  alterations 
affecting  this  tissue  in  pernicious  anemia  (p.  424)  and  leukemia  (p.  427). 
Muir^  and  others  have  shown  that  certain  medicaments  increase  the 

1  Hektoen,  "Amer.  Jour,  of  Med.  Sci.,"  May,  1903.  Poncet  and  Lereish, 
"Revue  de  Chit.,"  Dec.  10,  1903,  p.  657.  Balme  and  Reid,  "Practitioner,"  Dec, 
1Q04,  p.  780. 

2  Jour,  of  Path,  and  Bact.,"  Nov.,  1901.  See  also  Stockman  and  Chartens, 
"Tour,  of  Path,  and  Bact.,"  Dec,  1903,  p.  202. 


BOXKS     \S\)     JOINTS.  803 

number  of  erythroblasts.  and  possil)!)-  in  other  ways  stimulate  the 
hematogenic  fumtions  of  tlie  ineduUary  tissues.  Ilenke  lias  specially 
investijijated  the  bactericidal  properties  of  the  marrow,  and  a  number  of 
observers'  have  demonstrated  that  it  undergoes  important  changes  in 
certain  into.xications  and  many  infections.  In  acute  infections  the 
leukocyte-forming  function  is  usually  stimulated,  areas  of  necrosis  are 
commonly  present,  and  the  ])hagocytic  qualities  of  the  marrow  are 
increased.  In  chronic  infections  fatty  marrow  is  sometimes  replaced 
bv  the  more  cellular  form  and  evidences  of  increased  hematr)genesis  are 
occasionally  iiu;rkcd.  , 

Hemorrhage  under  the  periosteum,  giving  ri.se  to  more  or  less  de- 
tachment of  the  membrane,  occurs  in  scurvy,  and  other  blood  dyscrasias, 
and  in  cephalhematoma;  the  last-named  condition  results  from  the 
trauma  of  labor.  The  extent  of  the  hemorrhage  largely  depends  upon 
its  cause,  and  upon  the  resistance  of  the  individual.  In  marked  cases  of 
infantile  scurvy  the  periosteum  may  be  dissected  loose  from  the  bone 
over  a  large  area,  so  that  the  shaft  of  the  femur,  for  example,  may  show 
a  periosteal  attachment  at  each  end  only,  the  intermediate  area  having 
been  detached  by  the  blood-clot.  The  immediate  sequences  and  ulti- 
mate results  of  such  hemorrhage  largely  depend  upon  the  ])resence  or 
absence  of  infection.  When  bacteria  or  bacterial  products  are  excluded, 
death  of  the  bone  is  usually  averted,  more  or  less  absorption,  and,  later, 
organization  of  the  effused  blood  taking  place.  In  the  presence  of  in- 
fection, suppuration  with  extensive  necrosis,  septicemia,  pyemia,  and 
death  constitute  the  ordinary  sequence  of  events. 

Periostitis. — Inflammation  of  the  periosteum  may  be  acute  or  chronic, 
siniplr  or  ihviiiijcctii'c  and  unassociated  with  the  presence  of  bacteria, 
or  it  nia\"  lie  .^npf^iiritlirc. 

Acute  Simple  Periostitis. — Under  this  head  must  be  grouped  the  more 
or  less  trifling  inflammatory  and  reparative  changes  resulting  from 
bruises  and  other  injuries  of  the  periosteum,  and  unattended  by  in- 
fection. 

Under  such  circumstances  the  periosteum  is  swollen,  and  may  be 
separated  from  the  underlying  bone  Viy  sub])eriosteal  hemorrhage.  The 
density  of  the  periosteum  militates  against  the  occurrence  of  marked 
redness  and  injection,  although  they  may  be  ])resent.  Quickly  following 
the  injury  and  hemorrhage,  absorption  of  the  blood  begins;  this  is 
accompanied  by  a  varying  amount  of  proliferation  of  the  connective 
tissue,  including  the  genetic  layer  of  the  periosteum,  with  more  or  less 
leukocytic  infiltration.  The  extruded  blood  is  largely  removed  through 
the  activity  of  phagocytes,  and  the  resulting  cellular  accumulation 
proceeds  to  the  formation  of  cicatricial  tissue,  which  may  become  calcified 
or  be  converted  into  bone  by  the  osteolilastic  elements  present  in  the 
periosteum. 

Acute  suppurative  periostitis  commonly  follows  trauma  with  infection, 
although  mycotic  lodgment  in  the  ]>eriosteal  structures  may  occasionally 
occur  without  any  antecedent  injury  .sutliciently  important  to  be  recalled 

'  Muir  "Trans  Path.  Soc.  of  Ivondon."  IQ02,  vol.  5^.  p.  370  Graag,  "La 
Presse  M6d.,"  Aug.  8.  1903.  Frankel,  "Mitteil.  a.  cV  GrcnzRebiet.  d.  Med.  u. 
Chir.,"  Bd.  xii.  No.  4.  Henke,  "Arch,  des  Sci.  hioloR  dc  Saint-PtHcrsbourg." 
1904,  tome  X,  No.  2.  Longcope,  "Bull,  of  the  Aver  Clin.  Lab.  of  the  Penna.  Hos- 
pital," Jan.,  1903.  No    2. 


8o4  SPECIAL    PATHOLOGY. 

by  the  patient  at  the  time  when  symptoms  first  manifest  themselves. 
It  may  be  secondary  to  osteomyeHtis. 

The  organisms  '  most  frequently  associated  with  this  condition 
are  the  pyogenic  cocci,  the  colon  bacillus,  the  pneumococcus,  the  gono- 
coccus,  occasionally  the  typhoid  bacillus,  and  less  frequently  other 
microbes.  Bacteria'  may  reach  the  point  of  colonization  by  means  of  the 
blood,  as  their  frequent  presence  in  the  circulation  is  now  conceded  by 
all  who  have  studied  the  question.  In  other  cases  the  infection  is 
direct,  as  bv  trauma.  The  periostitis  just  described  may  be  converted 
into  the  suppurati.ve  form  by  the  lodgment  of  bacteria  at  the  newly 
evolved  area  of  diminished  resistance.  When  a  preinfective  stage  is 
present,  the  changes  during  that  period  are  those  already  described  as 
present  in  the  acute  simple  form. 

With  the  inception  of  infection,   coagulation   and  liciuefaction   ne- 
croses promptly  occur  and  polymorphonuclear  leukocytes  accumulate 
in  large  numbers,  converting  the  inflammatory  exudate  into  pus.     This 
always   tends  to   extend,   usually  involving,   to   a   certain  extent,   the 
underlying  bone,  which  is  further  influenced  by  the  fact  that  the  nutri- 
tion to  its  periphery  is  imperilled  by  separation  of  the  periosteum.     The 
density  of  the  fibro-elastic  membrane  does  not  favor  the  easy  escape  of 
the  infective  material,   and   hence   the  latter  frequently   detaches  the 
periosteum  for  some  distance  beyond  the  original  area  of  involvement. 
The  rapidity  and  the  extent  of  the  process  depend  upon  the  suscep- 
tibihty  of  the  individual  and  upon  the  activity  or  rather  the  virulence  of 
the  infective  agent.     Thus,  in  debihtated  patients  trifling  initial  lesions 
may  be  followed  by  the  gravest  consequences,  and  when  lessened  pro- 
tective powers  are  associated  with  virulent  infection,  extensive  necrotic 
processes  commonly  ensue.     Occasionally,  the  suppuration  is  circum- 
scribed, the  bacteria  are  destroyed,  and  an  area  of  healed-in  suppuration 
is  formed.      In  other  instances  perforation  of  the  XJeriosteum  takes  place 
and  a  paraosteal  suppuration  follows.     The  extension  of  the  infective 
processes    may   be    rapid,    often    surrounding    a    contiguous    joint    and 
inducing    a   periarticular    abscess.     In   other    instances   the    condition 
leads  to  separation  of  the  epiphysis,  and  even  penetrates  the  joint,  or 
from  the  juxta-epiphyseal  hne,  may  involve  the  medulla  of  the  bone, 
inducing  thereby  a  more  or  less  typical  osteomyeHtis.     Occasionally, 
the  infective  process  is  further  complicated  by  the  presence  of  hemor- 
rhage, and  to  this  form  has  been  given  the  name  hemorrhagic  periostitis. 
A  chronic  inflammatory  process  occurs  in  the  periosteum,  and  has 
been  called  fibrous  periostitis.     It  is  at  times  to  be  regarded  as  a  con- 
sequence of  the  simple  acute  periosteal  inflammation;    in  other  cases 
syphilis  appears  to  be  the  cause ;   and  in  still  other  instances  it  is  secon- 
dary to    inflammatory   and    infectious  diseases    primarily  in   adjacent 
tissues.     It  is  essentially  chronic  from  the  beginning,  lasting  for  years, 
is  not  usually  associated  with  marked  symptoms  or  prominent  tissue 
changes,  and  but  rarely  is  transformed  into  a  more  grave  type  of  perios- 
teal disease. 

The  periosteum  is  thickened,  extremely  dense,  and  firmly  attached 
to  the  underlying  bone.  Calcareous  deposits  may  be  present  in  the 
newly  formed  sclerotic  tissue,  and  may  be  projected  into  attached  tendons 
and  fasciae,  giving  rise  to  calcified  masses  closely  resembling  the  results 
of  the  so-called  ossifying  periostitis.     (vSee  Figs.  399  and  400-)     In  the 


BONES     AND     loINTS. 


X05 


latter  condition  there  are  bony  outj^rowtlis  (osteophytes),  which  are  j)ro- 
jected  into  the  adjacent  tissues  and  sometimes  form  masses  of  unusual 
size.  Rarely,  the  outgrowth  is  uniform,  increasing  the  diameter  of  the 
bone;  and,  as  it  is  unassociated  with  a  corresponding  increase  in  length, 
thickening  and  other  deforming  processes  may  result.  The  compact 
layer  ahvavs  appears  considerably  thicker  than  the  normal  bone.  The 
formation  of  new  tissvie,  both  osseous  and 
fibrous,  has  led  to  the  condition  being  called 
chronic  productive  osteoperiostitis. 

Closclv  alhcd  lo  liic  suppurative  inflam- 
mations of  the  i)criosteum  is  periostitis  albu- 
minosa.  That  the  inflammation  is  essentiall\- 
of  infective  origin  is  indicated  by  the  frequency 
with  which  pyogenic  organisms  are  found  in 
the  e.xudate ;  and  that  the  infection  difTers  from 
the  ordinary  infective  processes  in  bone  is  fur- 
ther indicated  by  the  course  of  the  disease  and 
the  character  of  the  discharge.  The  inflam- 
mation is  not  usually  restricted  to  the  ])eri- 
osteum,  but  involves  the  adjacent  compact 
portion  of  the  bone  (osteitis)  or  the  bone- 
marrow  (osteomyelitis),  and  in  some  cases 
both.  The  discharge  often  manifests  but  little 
resemblance  to  pus,  although  it  frequently  con- 
tains pvogenic  organisms  and  a  considerable 
number  of  polymorphonuclear  leukocytes.  It 
is  rich  in  albumin  and  contains  some  sugar  and 
the  usual  bone  salts.  Ordinarily,  it  is  fluid  in 
character,  although  it  may  be  semifluid,  and 
on  standing  sometimes  coagulates  as  a  whole 
or  may  be  separated  into  layers,  the  u])per- 
most  of  which  appears  oily,  with  a  varying 
amount  of  coagulation  in  the  strata  below. 
Occasionally,  the  inflammatory  and  necrotic 
processes  are  |)artly  enca])sulated. 

Anemia,  hyperemia,  and  congestion  of  bone 
are  of  little  pathologic  importance  when  con- 
sidered as  simple  processes.  The  absence  of 
elasticity  prevents  any  unusual  degree  of  vas- 
cular distention,  and  therefore  limits  the  possi- 
bility of  abundant  arterial  influx  or  venous 
accumulation.  This  statement  does  not 
imply  that  the  amount  of  blood  within  the  p,^  jpc^-cuROMr  rRn„tcT,vE 
bone   can    not    vary.       Variations,    however.  Ostko  periostitis. 

are  slight,  and  even  with  extensive  inflam- 
matory processes  the  evidence  of  va.scular  distention  may  be  wanting. 
In  general  anemia,  and  when  obliterative  lesions  in  the  blood-vessels, 
such  as  result  from  syphilis,  have  affected  the  arteries  leading  to 
the  bone,  a  varving  amount  of  anemia  may  occasionally  be  recog- 
nized. During  the  active  stage  of  osseous  evolution  and  growth,  and 
before  the  completion  of  development,  the  blood-supply  to  the  bones 
is  relativelv  abundant.     With  completion  of  the  osseous  matrix,  and 


8o6  SPECIAL    PATHOLOGY. 

later,  when  marrow  transformation  has  been  accomphshed,  the  amount 
of  blood  present  in  the  bone  is  greatly  diminished.  During  various 
processes  the  blood-supply  is  manifestly  increased,  and  retardation  of 
exit  may  intensify  vascular  distention,  but  the  inelasticity  of  the  Haver- 
sian canals  more  or  less  limits  even  inflammatory  hyperemia.  The 
changes  in  the  bone-marrow  seen  in  pernicious  anemia  have  been  regarded 
by  some  authorities  as  evidence  of  hyperemia.  The  conversion  of  the 
fatty  marrow  into  the  richly  cellular  marrow,  as  is  sometimes  seen  in 
that  disease,  as  well  as  in  leukemia,  certainly  implies  an  increased  blood- 
supply  ;  but  here  the  increased  supply  of  blood  constitutes  a  part  of  the 
local  formation  of  new  marrow,  and  is  scarcely  to  be  considered,  in  the 
present  state  of  our  knowledge,  as  a  primary  medullary  process. 

Hypertrophy  of  Bone. — In  giants  the  extensive  overgrowth  of  bone 
is  regarded  by  some  as  essentially  a  process  of  hypertrophy.  As  is  well 
known,  this  is  at  times  remarkably  symmetric  and  universal;  in  other 
instances  the  osseous  overgrowth  is  restricted  to  one  or  more  bones,  and 
sometimes  to  the  bones  of  a  single  member  or  to  a  single  bone.  The 
cause  is  unknown. 

Acromegaly/  or  pachyacria,  is  a  disease  associated  with  increase  in 
thickness  and  length  in  the  long  bones,  with  more  or  less  alteration  in 
many  of  the  small  bones.  That  the  fiat  bones  are  similarly  affected  is 
shown  by  the  increase  in  size  of  the  facial  sinuses.  The  lower  jaw  in- 
creases in  length  and  thickness  (prognathous  jaw),  and  may  be  projected 
so  far  forward  as  no  longer  to  articulate  with  the  superior  maxilla.  The 
osseous  overgrowth  is  usually  symmetric.  The  spine  suffers  a  varying 
degree  of  dorsal  kyphosis.  In  many  cases  the  pelvic  bones  and  the 
sternum  are  thickened ;  the  diameters  of  the  clavicles  are  increased  and 
sometimes  these  bones  are  slightly  elongated.  The  anteroposterior 
diameter  of  the  chest  is  augmented  as  a  result  of  the  lengthening  of  the 
ribs  and  posterior  curvature  of  the  spine.  The  slight  bulging  backward 
of  the  spine  and  projection  of  the  sternum  forward,  with  the  drooping 
head  and  prognathism,  constitute  the  ape-like  deformity  of  this  disease. 
The  bones  of  the  hand  are  enlarged  and  sHghtly  lengthened,  giving  rise 
to  the  battledore  hand  presumed  to  be  quite  characteristic  of  acromegaly. 
In  acromegaly  the  hypophysis  cerebri  frequently  shows  some  abnormal- 
ity: it  is  sometimes' the  seat  of  a  tumor,  while  in  other  cases  the  en- 
largement seems  to  be  proHferative  in  character.  The  constancy  with 
which  changes  are  found  in  the  hypophysis  would  naturally  lead  to  the 
beHef  that  this  organ  is  the  seat  of  the  primary  lesion,  but  similar,  if  not 
identical,  alterations  have  been  found  in  the  pituitary  body  without 
the  osseous  phenomena  of  acromegaly.  Nearly  fifteen  years  ago  Cun- 
ningham expressed  the  conviction  that  there  was  some  relation  between 
acromegaly  and  giantism,  a  view  that  has  been  steadily  gaining  ground. 
Giants  frequently  develop  acromegaly,  and  it  is  probable  that,  whatever 
may  be  the  cause  of  pachyacria,  if  it  act  prior  to  ossification  of  the 
epiphyses  a  giant  is  produced;  if  its  influence  be  delayed  until  the 
epiphyses  are  united,  acromegaly  results.  When  the  causative  factor 
continues  to  operate,  the  giant  finally  develops  some  of  the  phenomena 
of  acromegaly.  There  is  no  adequate  reason  for  placing  acromegaly  with 
1  Bassoe,  'Jour,  of  Nerv.  and  Mental  Disease,"  Oct.,  1903,  p.  596.  Launois 
and  Roy,  "Etudes  Biologiques  sur  les  Geantes,"  Paris,  1904.  Cunningham  and 
others,  "Brit.  Med.  Tour.,"  Nov.  19,  1904,  p.  1379. 


BONES    AND    JOINTS. 


807 


diseases  of  the  hones,  as  many  of  the  soft  tissues  are  ef[ually  involved; 
the  visrera  are  loninionly  cnlar,t,'ed.      It  is  probable  that  leontiasis  ossea 
and  hemihypertrophy  of  the  face  are  processes  closely  allied  to  acrome- 
galy, although  at  present  we  can  in  no  way  designate  the  character  of 
the  relationship. 

Pulmonary  hypertrophic  osteoarthropathy'  is  a  condition  presenting 
some  of  the  characters  of  acromegaly,  but  is  probably  a  distinct  affection. 
The  club  deformity  of  the  hand  is  absent  in  acromegaly  and  the  pro- 
cess is  symmetric.  In  the  disease  under  consideration  the  bones  of  the 
cranium  are  not  involved.  Marie,  who  first  described  the  disease, 
believed  it  was  due  to  the  absorption  of  some  substance   from  the  lungs 


Prominence  of  the  n>r*  with  bru.iilcnin«  ui  liu-  al.c.  i-xii-rnal  ^lrabislIlu^,  ijri>gn.il}itsni.  lutiUtiori.-  hancU,  unusual 
increase  in  the  lenjjth  of  the  long  Ixincs  (height  of  patient,  S  feet  6  inches),  dorsal  kyphosis,  and  markc<l  mus- 
cular wasting  are  present  in  this  case.  The  enormous  length  of  the  arms  can  be  appreciated  when  it  is  stated 
that  the  patient's  reach  is  8  feet  o  inches;   from  crotch  to  heel  the  measurement  is  4  feet  10  inches. 


and  pleura,  the  seat  of  an  inflammatory  process;  he  therefore  called 
the  disease  osteoarthropathic  Itypertrophiatitc  pncuvioniqiic .  Godlee  be- 
lieves that  a  number  of  conditions  are  included  under  the  one  name; 
in  his  patient  the  symptoms  of  pulmonary  osteoarthropathy  disap- 
peared after  a  long-standing  empyema  had  discharged  through  a  bron- 
chus;   the  toxic  nature  of  the  affection  is  generally   accepted. 

A  peculiar  form  of  bony  overgrowth  is  seen  in  leontiasis  ossea.  In 
this  condition  there  is  a  symmetric  enlargement  of  the  facial  bones. 

'  Janeway,  "  Anier.  jour,  of  Med.  Sci."  Oct..  190.3.  Symes-Thompson.  "  Royal 
Med.  and  Chir.  Soc.."  Jan.  12,  1004:  "Brit.  Med.  Jour.."  Jan.  16,  1904,  p.  134. 
Wynn,  "Birmingham  Med.  Review,"  .April  and  May.  1904. 


So8 


SPECIAL    PATHOLOGY. 


The  lower  jaw  is  but  slightly  involved,  while  the  bones  of  the  trunk  and 
extremities  escape. 

Aside  from  the  conditions  just  described,  there  is  occasionally  ob- 
served evidence  of  osseous  overgrowth  that  can  not  be  properly  con- 
sidered with  any  of  the  foregoing  conditions.  As  an  example  of  this 
morbid  condition  may  be  cited  certain  local  overgrowths  of  bone  closely 
resembling  tumors.     These  are  sometimes  projected  from  the  compact 


D 


Fig.  397. — Osteophytes  on  the  Popliteal  Aspect  of  the  Lower  End  of  the  Femur. 
A .  Articular  surfaces.    B.  Compact  osteophyte.    C.  Spongy  osteophyte  undergoing  caries  as  a  result  of  ulcera- 
tion of  the  overlying  soft  parts  and  extension  of  infection  to  the  bone.     To  the  right  of  Z)  is  a  spicular  osteophyte, 
and  just  below  is  a  boss,  e\idently  illustrating  an  earlier  stage  in  osteophytic  growth. 


portion  of  the  bone  into  the  marrow  cavity,  constituting  enostoses; 
more  commonly  growths  upon  the  surface  of  the  bone  extend  outward 
into  the  adjacent  tissues;  when  small,  these  are  called  osteophytes, 
and  if  large,  exostoses.  F^r^  and  Deniker  *  have  called  attention  to 
symmetric  exostoses  for  which  there  is  no  satisfactory^  explanation. 
When  arising  purely  from  the  periosteum,  and  particularly  when  the 
origin  is  from  the  superficial  layer,  which  has  feeble  bone-producing 

'  "Revue  de  Chir.,"  April  10,  1904,  p.  544. 


BONES    AND    JOINTS.  809 

powers,  these  masses  nia\'  be  nioxalile.  I'iuKt  such  circumstances  they 
are  sometimes  called  periostoses.  The  growth  of  bone  alonj;  the  course 
of  tendinous  attacliment  is  by  some  regarded  as  a  form  of  hypertrophy. 
The  osseous  overgrowth  resulting  from  inflammation,  infection,  and 
injury  had  ])robal)ly  best  be  considered  with  those  processes.  The 
hyperplasia  resulting  from  the  administration  of  such  agents  as  arsenic 
ainl  phosphorus  merits  no  special  consideration. 

Atrophy  of  Bone. — Occasionally,  atrojdiic  processes  begin  in  the 
osseous  layer  adjacent  to  the  medulla,  or  in  the  Haversian  lamclhe,  and 
])rogrcss  towanl  the  periphery,  constituting  what  is  termed  cccoitric 
atrophy.  On  the  other  hand,  the  process  may  begin  immediately  under 
the  periosteum,  lessening  the  circumference  of  the  bone,  and  in  this  form 
it  is  called  concentric  atrophy.  In  other  forms  of  atrophy  the  osseous 
absorption  occurs  along  the  lines  of  the  Haversian  canals,  and  also  in- 
volves, to  a  varying  degree,  the  spongy  layer.  As  a  result  of  the  widening 
of  the  Haversian  canals,  the  bone  appears  sy)ongy  or  porous,  and  the  con- 
dition has  received  the  name  osteoporosis;  the  absorption  following  the 
course  of  the  Haversian  system  has  led  to  its  being  known  as  Haversian 
atrophy.  As  the  disease  is  usually  associated  with  conversion  of  the  mar- 
row into  fattv  tissue,  it  has  been  termed — probably  incorrectl\ — fatty 
degeneration  of  bone.  Senile  atrophy^  attacks  more  particularly  the  vault 
of  the  skull  the  scapula,  and  the  pelvis — in  other  words,  the  flat  bones. 
It  is  also  seen  in  the  inferior  maxilla,  and  is  of  ten  conspicuous  in  the  alveolar 
process.  As  a  result  of  eccentric  and  concentric  atrophies  the  strength 
of  the  long  bones  may  be  materially  lessened  (fragilitas  ossium-),  favoring 
the  occurrence  of  fractures.  Disease  and  injuries  involving  the  s])inal 
cord  and  nerve-trunks  are  sometimes  followed  Ijy  atrophic  y^rocesses, 
neuropathic  atrophy,  particularly  in  the  long  bones  at  or  near  the  articu- 
lar extremities.  Injury  and  disease  of  contiguous  structures  or  the  bone 
itself  are  sometimes  attended  by  atrophy ;  when  due  to  the  hrst-narned 
cause,  the  condition  is  called  traumatic  atrophy,^  and  when  resulting 
from  inflammation,  inflammatory  atrophy.'* 

Pressure  atropliy  of  the  bone  commonly  results  from  constantly 
applied  pressure,  even  of  a  moderate  degree.  Pressure  of  cicatrices, 
rapidlv  growing  tumors,  aneur>\sm,  and  fluid  accumulation  in  cavities 
surrounded  by  bone,  as  in  the  air  sinuses  of  the  face,  may  be  mentioned 
as  causes  of  pressure  atrophy.  The  aneurysm  shown  in  figure  206.  page 
532,  had  caused  pressure  atrophy  of  the  bodies  of  the  vertel)ra.-.  A 
condition  closely  allied  to  pressure  atrophy  is  the  osseous  resorption 
resulting  from  tumor  formation  or  chronic  infectious  processes  in  the 
interior  of  the  l)one,  as  not  infrequently  occurs  in  the  inferior  maxilla, 
where  neoplastic  destruction  of  the  interior  is  accompanied  by  continuous 
periosteal  proliferation  and  external  apposition.  A  similar  condition 
is  at  times  observed  in  the  long  l)ones  as  a  result  of  tumors  originat- 
ing in  the  mc<lullary  space.  Under  such  circumstances  the  bone  may 
assume  enormous  proportions.     The  femur,  for  example,  is  sometimes 

'Weber,     "Brit.   Med.    lour.."   Jan.    21.    1905.   p.    120. 

'Biggs.  "Univ.  of  Penna.  Med.  Bull.,"  Feb..  1903.    Smith."  Brit.  Mcdjuur.. 
Oct.  ^.  1901,  p.  824-  ,  „, 

'Imbert  and  Gagni^rc.  "  Bulle.  Officiel  de  la  Soc.  Franyaise  d  hlectrotherapje 
et  de  Radiologic,"  Julv  and  Aug..  1904. 

♦Sudeck.    'Deut.  mc«l.  Woch,"  May  8.  1902 


SPECIAL    PATHOLOGY, 


SO  enlarged  that  it  measures  from  12  to  15  cm.  in  diameter  and  may 
possess  externally  a  layer  of  compact  bone  varying  in  thickness,  but 
rarelv  approaching  0.5  cm. 

Halisteresis  is  probably  not  a  true  atrophic  process,  although  it  is 
usually  considered  as  one  of  the  forms  of  osseous  atrophy,  and  consists, 
for  the  most  part,  in  the  removal  of  the  lime  salts  with  subsequent 
changes  in  the  osseous  matrix.  Occasionally  it  is  a  more  or  less  local 
affection  occurring  in  the  neighborhood  of  some  invading  processes,  or 
it  may  be  general,  in  which  case  it  constitutes  the  disease  called  osteo- 
malacia, mollities  ossium  or  malacosteon. 

While  osteomalacia^  is  a  disease  of  adults,  juvenile  and  senile  forms 
occur.  It  is  most  frequently  observed  in  females,  and  is  recognized  as 
one  of  the  possible  complications  of  pregnancy.  Lactation,  particularly 
when  prolonged,  is  believed  to  be  a  determining  factor.  The  fact  that 
it  is  endemic  in  certain  localities  has  led  many  to  believe  that  it  is  in- 
fectious in  origin;  Moussu  and  Charrin  have  apparently  proved  that 
osteomalacia  is  transmissible.  In  the  puerperal  form  it  is  first  manifest 
in  the  bones  of  the  pelvis,  to  which  structure  it  may  be  confined;  in  other 
cases  it  begins  in  the  bodies  of  the  vertebra,  and  the  first  evidence  is 
the  occurrence  of  lordosis,  kyphosis,  or  scoliosis.  The  bone-marrow  is 
hyperemic,  and  may  contain  areas  of  hemorrhage.  It  is  usually  richly 
cellular,  and  sometimes  contains  cysts.  When  advanced,  the  bodies  of 
the  vertebra  "may  be  squeezed  out  like  a  sponge,"  and  the  ribs  are  easily 
bent  inward.  In  "the  long  bones  the  osseous  wall  is  sometimes  no  thicker 
than  a  sheet  of  paper,  and  can  be  easily  indented  by  the  finger.  The 
pelvic  deformitv  is  commonly  quite  characteristic:  the  acetabulum  is 
pushed  inward,  the  iliac  crest  is  pulled  outward,  the  promontory  of  the 
sacrum  and  the  pubic  articulation  are  thrust  abruptly  forward.  Frac- 
tures occur,  and  may  be  repaired,  even  during  the  activity  of  the  process. 

Early  in  the  disease  the  histologic  changes  are  inconspicuous.  The 
bone  salts  are  removed,  and  usually  appear  in  excess  in  the  urine.  The 
first  solution  of  the  lime  salts  appears  to  occur  at  the  periphery  of  the 
trabeculae  and  around  the  Haversian  canals.  The  process  may  there- 
fore be  considered  a  decalcification  of  the  bone,  but  later  the  decalcified 
matrix  is  in  part  absorbed;  or  it  may  be  converted  into  a  coarsely 
fibrous  structure. 

Inflammation  of  Bone. — As  a  rule,  periostitis  causes  a  certain  amount 
of  inflammation  in  the  adjacent  osseous  structures,  and  inflammation 
of  the  bone,  approaching  the  periosteum,  implicates  that  membrane. 
The  classification  and  subdivisions  of  bone  inflammation  embrace:  (i) 
Inflammation  of  the  compact  portion  of  the  bone  or  of  the_  osseous 
structure  properly  so  called — a  condition  termed  osteitis  or  ostitis;  (2) 
an  inflammation  originating  in,  or  extending  to,  the  medullary  struc- 
tures, and  hence  called  osteomyelitis.  Periostitis,  osteitis,  and  osteomy.- 
elitis  are  frequently  concurrent. 

The  most  important  of  these  bone  inflammations  is  osteomyelitis. - 

>  Tashiro,  "Ziegler's  Beitr.,"  Bd.  -,4,  H.  2,  p.  220.  Pierart,  These  de  Paris, 
1904.  Honicke.  •'Berlin,  klin.  Woch.."  Oct.  31,  1904.  Thos.  A.  and  D.  J.  Davis, 
"Annals  of  Surgery,"  Aug.,  1904.  Moussti  and  Charrin,  "C.  R.  Soc.  de  Biol.," 
May  7,  1904,  p.  778. 

"2Hencke,  "Centralbl.  f.  Bakt.,"  Bd.  xxxiii,  H.  8,  p.  697:  and  '  Arch,  de 
Sci.  Biol.,"  1903,  vol.  10,  fasc.  2.  p.  171.  Nichols,  "Jour.  Amer.  Med.  Assoc," 
Feb.  13,  1904,  p.  439.     Durbach,  "Miinch.  med.  Woch.,"  Sept.  20,  1004,  p.  16S9. 


boNHS     AND    JOINTS.  8ir 

The  process  is  essentially  an  infection  invcjlving,  at  Hrst,  the  softer  and 
more  richlv  cellular  parts  of  the  V)one.  The  organisms  most  frequently 
present  are  the  staphylococci,  and  usually  the  staphylococcus  pyogenes 
aureus.  In  a  certain  ])ercentage  of  cases  the  streptococcus  is  the  in- 
fecting microbe.  Osteomyelitis  depending  upon  the  presence  of  the 
pneumococcus,  the  Bacillus  typhosus,  the  Bacillus  coli  communis,  the 
i)acillus  of  influenza,  and  occasionally  other  organisms,  occurs.  A  true 
tuberculous  osteomyelitis  depends,  of  course,  upon  the  tubercle  bacillus. 
The  portal  of  entry  and  the  route  followed  by  the  invading  organism 
varv  in  ditTerent  cases.  Compound  fractures  and  wounds  exposing  the 
osseous  tissues  to  bacteria-laden  agents  may  be  taken  as  a  type  of  direct 
infection.  In  preantiseptic  days  the  disastrous  results  of  compound 
fractures  were  due  to  the  introduction  of  bacteria  and  the  occurrence  of 
an  initial  osteomyelitis  that  rapidly  became  part  of  a  general  septic 
process.  It  has  been  abundantly  shown,  however,  that  direct  infection 
is  not  necessarv  to  the  occurrence  of  osteomyelitis,  as  the  bacteria  may 
reach  the  bone  in  other  ways.  Injury  of  the  bone  favors  the  occurrence 
of  infection  bv  the  production  of  a  point  of  least  resistance,  in  which 
bacterial  colonization  is  readily  accomplished.  A  solution  of  continuity 
in  the  skin,  such  as  is  afTorded  by  an  abrasion  or  a  superficial  wound, 
may  offer  sufficient  facility  for  bacterial  ingress.  In  other  cases  no  such 
external  atrium  can  be  demonstrated.  In  these  instances  it  is  generally 
believed  that  the  bacteria  enter  the  circulation  by  means  of  the  respira- 
tors apparatus,  or,  probably  in  a  larger  percentage  of  cases,  by  the 
alimentarv  canal.  The  pharynx  and  tonsils  are  also  known  to  be 
portals  of  entry.  The  disease  is  most  common  in  the  young,  being 
especially  frequent  in  adolescence.  It  occurs,  however,  in  infancy, 
and  less  commonly  in  middle  life  or  in  old  age.  The  frequency  with 
which  the  young  are  attacked  is  probably  owing  to  the  character  and 
abundance  of  the  vascular  supply  to  the  growing  bone  and  on  account 
of  the  very  frequent  occurrence  of  injury.  A  special  form  of  osteomy- 
elitis' occurs  in  workers  in  mother-of-pearl. 

Initially,  the  di.sease  attacks  most  frequently  the  long  bones — 
the  femur,  tibia,  humerus,  and  bones  of  the  forearm,  in  the  order 
given.  It  mav  be  first  manifested  in  the  periosteum  (periostitis), 
reaching  the  medullary  cavity  through  the  Haversian  canals  or  the 
juxta-epiphvseal  disc.  The  latter  point  is  sometimes  the  beginning,  and. 
occasionallv.  the  disease  remains  limited  to  this  area,  constituting  a  form 
of  osteomyelitis  known  as  acute  infectious  epiphysitis.  The  vascularity 
of  this  area  and  its  richness  in  venous  ]>Iexuscs,  as  well  as  its  liability  to 
injury,  render  it  unusually  susceptible.  Although  the  long  bones  are 
usuallv  attacked,  other  osseous  structures  are  by  no  means  immune; 
the  round  bones  of  the  carpus  and  tarsus,  the  flat  bones  of  the  skull, 
and  the  bodies  of  the  vertebra  are  sometimes  involved. 

With  the  entrance  of  the  invading  organism  inflammatory  processes 
are  at  once  inaugurated.  There  is  more  or  less  vascular  distention,  as- 
sociated with  thrombosis  of  many  of  the  vessels;  rapid  and  extensive 
leukocvtic  invasion;  coagulation  necrosis,  followed  by  liquefaction  of  the 
intercellular  substance;    and  destruction  of  the  tissue,  leading  to  the 

Courmont  and  Lcsicur,  "Lyon  M<?d.."  Dec.  iS.  1904.     Bernard.  "Trans,  of  Path. 
Soc.  of  London."  ioo3-     Giivot,  "  Revue  dc  Chir  ,"  Feb.  10.  1004.  P   271- 
'  Broca  and  Tridon,  "  Revue  de  Chir.."  Oct.  10.  1903.  p.  411 


8i2  SPECIAL    PATHOLOGY. 

development  of  purulent  foci.  Coalescence  of  these  areas  of  suppuration, 
as  well  as  extension  along  the  tract  of  the  marrow,  lead  to  rapid  disinte- 
gration of  this  substance.  The  extent  of  damage  depends,  as  in  most 
cases  of  infection,  upon  the  virulence  of  the  invading  organism  and  the 
activity  of  the  protective  forces.  In  some  instances  the  latter  are  in- 
sufficient, and  the  entire  narrow  cavity  of  the  bone  yields  before  the 
rapidly  advancing  process.  The  inflammation  reaches  and  involves 
the  periosteum,  which  often  becomes  detached;  the  nutrient  vessels  are 
thrombosed,  and  death  (necrosis)  of  a  part,  or  of  the  entire  bone  follows. 
With  inflammation  of  the  epiphysis  penetration  of  the  contiguous  joint 
may  occur,  followed  bv  suppurative  arthritis.  This  suppuration  not 
uncommonly  breaks  through  the  periosteum,  inducing  a  paraosteal 
abscess  that  burrows  along  the  line  of  least  resistance  and  eventually 
reaches  the  skin,  through  which  it  ruptures.  The  dead  bone  is  called  a 
sequestrum. 

As  a  result  of  the  septic  thrombophlebitis,  systemic  dissemination  of 
bacteria,  with  or  without  infective  emboli,  frequently  induces  the 
gravest  form  of  septicemia  or  pyemia.  The  evidences  of  intoxication 
are  sometimes  pronounced,  and  death,  from  the  overwhelming  character 
of  the  poison,  may  precede  gross  evidence  of  the  infective  processes  in 
the  bone  involved'.  Should  the  patient  survive  the  more  acute  inflam- 
matory phenomena,  separation  of  the  dead  part,  and  attempted  regen- 
eration of  the  bone  are  sooner  or  later  inaugurated.  (See  Caries  and 
Necrosis,  p.  812.) 

In  some  instances  the  infective  process  is  limited,  constituting  a 
condition  spoken  of  as  circumscribed  osteomyelitis  or  osteal  abscess. 
Such  abscesses  maybe  extremely  minute,  rarely  exceed  from  1.5  cm. 
to  2.5  cm.  in  diameter.  They  occur  in  the  cancellous  structures  of  the 
long  bones,  and  are  more  common  in  the  upper  end  of  the  tibia  than 
in  all  other  situations  put  together.  Osteal  abscesses  of  long  duration 
are  usually  surrounded  by  a  zone  of  sclerotic  or  indurated  bone  of  the 
densest  character,  and  after  such  effort  at  encapsulation  often  remain 
quiescent  for  an  indefinite  period.  On  the  other  hand,  injury,  weak- 
ened resistance,  or  possibly  other  causes  sometimes  lead  to  recrudes- 
cence of  a  previously  inactive  focus. 

After  the  acute  stage  of  osteomyelitis,  whether  circumscribed  or 
diftused,  and  also,  though  less  frequently,  after  the  subacute  or  even 
the  chronic  form,  partly  localized  and  persistent  subacute  or  chronic 
infective,  processes  may  remain.  These  are  commonly  manifested  by 
the  presence  of  sinuses  communicating  with  the  external  surface,  and  from 
which  pus  is  discharged;  or,  less  frequently,  as  in  diseases  of  the  pelvic 
bones,  with  some  hollow  viscus,  such  as  the  bladder  or  rectum.  Such 
sinuses  are  walled  by  granulation  tissue,  and  usually  communicate  with 
some  cavity  in  the  bone  or  an  area  of  suppuration  involving  its  exterior. 

Caries  and  Necrosis. — The  term  slough  is  usually  applied  to  masses  of 
dead  tissue  arising  in  the  soft  parts  and  undergoing  separation  from 
adjacent  living  structures.  In  osseous  tissue  the  process  by  which  the 
bone  is  destroyed — in  other  words,  the  alterations  terminating  in  the 
death  of  a  perceptible  mass  of  bone — is  called  necrosis  or  death  of  the 
bone  en  masse.  In  the  soft  parts  the  lesion  accompanying  and  follow- 
ing the  separation  of  the  slough,  and  limited  to  the  adjacent  living 
tissues,  is  called  ulceration.  In  bone  essentially  the  same  process  is 
termed  caries. 


BONKS     AND    JOINTS. 


Sr.^ 


C'atisis.  -Deatli  oi  the  l)()nc  as  a  result  of  osteoniyt'litis  has  alrcadx 
been  (.onsidered.  Periosteal  sei)aration,  embolism  and  thrombosis,  and 
detachment  of  fraj^mients  of  l)one  from  the  vascular  structures  from 
which  they  normally  receive  their  nutrition  may  cause  necrosis.  The 
jmncipal  cause  of  necrosis  is  infection.  This  may  assume  tlie  jjeneral 
characters  already  described  when  considering  osteomyelitis,  or  may  be 
a  chronic  infectious  ])rocess,  such  as  tuberculosis  and  actinomvcosis, 
or,  less  freciuently,  such  bacterial  invasion  of  the  bone  as  mav  arise  from 


Fig.  3Q8,--OsTF.oMYKLms  Involving  thk  Tibia  and,  n>  a 

LiUITKD  KXTKNT,  THE  LoWKK   l.SU  OF  THK  KeMIR.       (Thc 

disi-xsc  lx-K.in  ;ii  or  ne;ir  thc  epiphysis,  and  the  case  Wiis  re- 
portoi  under  the  title  of  acute  infectious  epiphysitis.  Thc 
limb  was  amputatetJ  and  thc  p;ilient  recovered.  For  de- 
tailetl  report  see  ".Medical  News,"  .\uKUSt  13,  1802.) 
A.  Patella  turned  backward  and  to  one  side,  showing  its  lower 
surface.  U.  The  lower  extremity  of  the  femur,  showing  the 
line  of  the  cpiphy.sis  and  a  distinct  tx)rder  of  fatty  degenera- 
tion just  where  the  epiphysis  joins  the  shaft.  In  the  lower 
e-Ttremity  of  the  femur  .ire  s<.-veral  small  round  or  irregular 
dots  marking  the  position  of  abscesses  in  the  l>onc.  The 
periosteum  of  the  femur  is  slightly  thickened  just  alx)vc  the 
epiphyseal  line.  The  epiphysis  is  nonn;U,  except  that  the 
cartilage  covering  it  is  supcrlicially  crodixl.  C,  1),  E.  Sawed 
section  of  thc  libia.  showing  thc  condition  of  its  medul- 
lar)' canal;  at  the  upper  extremity  of  thc  tibia  thc  shaft  ter- 
minates in  a  jagged,  irregular  extremity  that  has  been  in 
apposition  with  the  epiphysis.  Thc  epiphysis  is  placed  over 
■  on  one  side  at  H,  with  a  \iew  of  thc  upiier  surface,  while  at  I 
the  under  surface  is  shown.  Just  abxive  the  line  leading 
from  C  are  two  abscesses  of  considerable  size;  Iwlow  this 
line,  and  extending  to  the  line  D,  is  to  l>e  noted  the  detach- 
ment of  the  periosteum.  The  periosteum  is  much  thickened, 
the  thickening  fading  off  ;is  (he  line  E  is  approacheti.  .\t  C 
thc  Ixinc-marrow  was  intensely  red  (hyjxremic)  and  there 
were  no  less  than  a  doZL-n  small  abscess  cavities;  the  largest 
of  these  was  not  0.5  cm.  in  diameter.  The  external  com- 
pact portion  of  the  Ixine  is  much  thickenal,  and  just  oppo- 
site the  leader  from  thc  letter  there  is  considerable  "swelling 
along  thc  line  of  thc  periosteum.  The  lower  epiphysis  of 
thc  libia  does  not  show  to  advantage;  at  the  lower  extremity 
of  the  shaft,  near  E.  can  be  seen  several  small  abscc-ss  cavi- 
ties. Thc  point  G  is  the  scat  of  the  original  injury.  F 
marks  the  metatarsophalangeal  articulation;  a  section  of 
thc  metatarsal  Ijone  has  Ix-en  made  and  the  upper  fragment 
has  been  ttime<i  downward.  Thc  great  toe  is  also  shown. 
H  is  a  Wcw  of  the  superior  surface  of  the  epiphysis  of  thc 
tibia — the  artimlar  surface.  It  contained  not  less  than  live 
or  six  sm.-iU  oijonings  that  communicalod  with  the  abscess 
Ik-Iow  and  with  the  joint  above.  In  some  of  them  sm.all 
fragments  of  necrotic  Ume  arc  to  be  obser\'ed.  The  carti- 
laginous structures  of  the  joint  arc  .also  entirely  destroyed, 
but  the  articular  margins  of  thc  epiphysis  show  a  slight  frag- 
ment of  thc  two  semilunar  cartil. !;.;.>.  I  j.,  the  same  .is  H, 
except  that  it  is  a  \icw  of  the  ill!  where  it  came 

in  contact  with  thc  libia.     It  «i  !  that  tlie  epi- 

physis hxs  been  converted  into  .1:  iiy,  the  wall  of 

which  is  formed  by  a  hard  cancclLilcJ  i.iycr  uf  bone  and  by 
thc  articular  dist.  There  was  no  periosteum  continuous 
with  thc  shaft  and  eiujihysis,  and  hence  i!i.  I.iticr  moved 
freely  uprin  the  enil  of  the  former,  ihi:  •., 

"tl.ail    joint"  so   ch.iracteristic    of   ep) 
The  interior  of  the   knee  contained  .1  j;   :, 

tity  of  pus,  and  thc  synovial  stnjcturi.a  wtre  Au>  di?- 
organizcd. 

the  metastases  of  the  typhoid  bacillus,  colon  bacillus,   and   influenza 
organism.     (See  Causes  of  Osteomyelitis,  p.  8ii.) 

Toxic  Necrosis. — A  form  of  necrosis  observed  in  laborers  in  match 
factories  is  usually  believed  to  be  distinct  from  the  other  types  of  bonie 
death,  and  is  called  phos{)horous  necrosis.  It  is  not  })rc)l»able,  however, 
that  there  is  any  material  difference  between  this  jtrocess  and  necroses 
arising  from  other  causes.  The  ])hosphorus  lessens  the  resisting  power 
of  the  tissues,  favors  infection,  and  as  opportynities  for  infection  are 


8l4  SPECIAL    PATHOLOGY. 

greatest  in  and  around  the  teeth  the  inferior  maxilla  is  most  frequently 
involved.  Caries  (cavity  formation  in  the  teeth)  seems  to  be  almost  a 
requisite,  and  is  constantly  present  when  the  necrosis  appears  early. 
Morbid  Anatomy  oj  Necrosis. — The  masses  of  necrotic  bone  vary  in 
size.  The  entire  shaft  of  a  long  bone — as,  for  example,  the  humerus— 
sometimes  exfoliates  in  one  piece,  or  the  epiphysis  alone  may  be  involved; 
not  infrequentlv  a  fragment  of  one  or  both  these  structures  is  cast  off. 
When  considering  gangrene  (see  p.  255),  attention  was  called  to  the  fact 
that  the  line  of  demarcation  is  an  irregular  zone,  one  side  of  which 
bounds  the  living  tissues  and  the  other  the  dead  structures,  and  that  the 
changes  occurring  within  this  area  were  those  incident  to  the  separation 
of  the  dead  from  the  living  structure,  essentially  a  process  of  ulceration. 
This  applies  to  the  line  of  demarcation  that  would  in  time  amputate  a 
limb,  as  well  as  to  the  line  of  demarcation  leading  to  the  separation  of  a 
scarcely  visible  slough.  Death  of  the  bone  and  the  process  of  separation 
from  the  viable  tissue  are  comparable  to  the  changes  already  noted  as 
present  in  the  soft  parts.  Where  the  dead  tissue  joins  the  living  there 
appear  accumulations  of  phagocytic  cells  which  attack  the  osseous 
matrix,  forming  the  hne  between  the  dead  and  living  structures,  and 
proceed  with  the  separation  of  the  necrotic  mass.  Many  of  these  cells 
are  clearlv  leukocvtes  belonging  to  the  phagocytes  already  described. 
(See  p.  98.)  Other  cells  resemble  the  giant  cells,  and  are  probably 
identical  with  the  mveloplaxes  of  osseous  absorption,  and  in  this  locality 
are  also  called  osteoclasts.  Through  the  secretory  and  phagocytic  action 
of  the  leukocytes  and  osteoclasts  the  dead  bone  is  separated  from  the 
living,  and  constitutes  the  sequestrum.  In  the  mean  time  suppurative 
processes  may  have  communicated  with  the  exterior  and  formed  sinuses, 
through  which,  if  the  piece  of  dead  bone  be  small,  it  may  escape.  Com- 
monly, the  surgeon  \ssists  nature  by  removal  of  the  sequestrum.  Oc- 
casionally, the  dead  i-.ass  is  surrounded  by  fibrous  or  osseous  tissue;  in 
other  words,  a  form  of  healing-in  may  occur. 

If  the  infection  is  not  arrested,  destruction  of  tissue  along  the  line  of 
separation  continues  after  exfoliation  of  the  dead  bone  has  taken  place, 
and,  as  rapidly  as  granulation  tissue  is  formed,  it  is  liquefied  by  the 
contained  bacteria  and  cells;  and,  in  this  way,  the  tendency  toward 
repair  is  constantly  opposed  by  the  necrotic  processes  contingent  upon 
the  presence  of  microorganisms.  This  constitutes  what  is  called  caries 
or  ulceration  of  bone.  The  c  ..^racter  of  the  pus  produced  by  such  an 
infection  depends  largely  up(,,  ^e  bacteria  present.  In  some  cases  the 
pus  is  abundant,  thin,  and  ,  a  in  pus-cells.  This  process  is  called 
caries  humida.  In  other  instances  the  amount  of  inflammatory  exudate 
may  be  small  and  the  discharge  quite  inconspicuous,  to  a  certain  extent 
justifying  the  name  commonly  applied — caries  sicca,  or  dry  caries. 

Regeneration  of  Bone. — During  or  after  the  separation  of  the  seques- 
trum, and  as  soon  as  the  activity  of  the  infection  will  permit,  the  ad- 
jacent osseous  tissue  begins  repair  by  the  production  of  new  bone.  The 
new  bone  is  commonly  evolved  from  the  periosteum,  and  therefore 
forms  around  the  sequestrum;  the  latter  may  be  covered,  except  that 
here  and  there  are  small  openings  through  which  the  pus  escapes ;  the 
persistence  of  the  suppuration  is  due  to  the  continuance  of  a  low  order 
of  infection,  probably  perpetuated  by  the  irritation  of  the  dead  bone. 
The    newlv    formed   bone    surrounding   the    sequestrum,    is    called    the 


1 


Hon  i;s    and    |i  h  n  i  s. 


815 


involucnim.  The  dead  bone  acts  as  an  irritant,  and  by  its  removal  and 
the  dismtection  of  tlie  area  involved,  or  sometimes  as  a  result  of  victory 
of  the  phagocytes  over  the  bacteria,  repair  proceeds  by  the  production 
of  new  osseous  tissue,  which  eventually  replaces  that  destroyed  by  the 
processes  of  necrosis  and  caries.  The  newly  formed  bone  is  never 
uniform,  smooth,  and  regular,  like  the  normal,  but  uneven  and  clumsy, 
and  but  a  crude  reproduction  of  the  destroyed  tissue. 

Chronic  Nonsuppurative  Inflammation  of  Bone. — In  osteomyelitis, 
both  acute  and  chronic,  and  in  caries  and  necrosis  the  lesion  is  usually 
due  to  bacteria,  the  specific  action  of  which  is  to  induce  sui)i)uration  or 
some  necrotic  and  degenerative  change,  such  as  caseation.  There  can  be 
no  doubt  that  in  bone  a  chronic  productive  process  occurs  which  is 
comparable  to  interstitial  fibroses  observed  in  other  organs.  The 
ditTerence,  however,  Hes  in  the  fact  that  the  interstitial  tissue  of  bone 
consists  of  a  calcified  matrix,  while  in  other  organs  it  is  composed  of  a 
fibrillated  structure.  This  particular  type  of  inflammation  is  prone  to 
occur  in  connection  with  syphilis,  often  when  syphilitic  processes  are 
latent,  and  is  frequently  associated  with  the  chronic  productive  peri- 
ostitis alreadv  described.  (See  Fibrous  Periostitis,  p.  804.)  It  is 
present  to  a  varying  degree  in  the  neighborhood  of  suppurative,  necrotic, 
and  infectious  lesions  involving  the  bone  or  paraosteal  structures;  it 
also  develops  around  bone  abscesses;  in  other  words,  chronic  productive 
osteitis  appears  to  result  from  the  presence  of  irritants  not  of  a  kind  or 
not  sutftcientlv  active  to  produce  suppuration. 

Morbid  Anatomy. — The  affected  bone  usually  increases  in  size  by 
apposition  of  new  osseous  or  osteoid  tissue  from  and  under  the  periosteum. 
At  the  same  time,  in  the  long  bones— as.  for  example,  the  femur — the 
marrow  cavitv  is  encroached  upon  and  may  be  entirely  replaced  by  new 
osseous  tissue.  (See  Fig.  400.)  The  new  tissue  i'  ^ommonly  hard  ;  the 
old  bone  also  becomes  dense.  The  density  is  sometimes  sufliciently 
intense  to  preclude  incision  by  a  chisel  or  saw,  and  as  such  masses  occur 
around  sequestra,  thev  frequently  give  rise  to  great  di faculty  during 
operations  for  the.  renioval  of  dead  bone.  On  account  of  the  extreme 
induration  of  the  bone  the  disease  has  received  the  name  osteosclero- 
sis. Bv  reason  of  its  apparent  inflammatory  origin  it  has  been  called 
condensing  osteitis.  (See  Figs.  399  and  400.)  In  inflammations, 
attended  bv  resorption  of  the  osseous  tissue  surrounding  the  Haversian 
canals  and' the  production  of  infiamnv  ry  elements  in  the  Haversian 
lymph  spaces,  the  bone  is  made  abno  .ly  porous  and  the  condition  is 
called  rarefying  osteitis.  In  bones  so  .cted  the  marrow  is  abnormally 
soft  and  red,  and  unusuallv  vascular. 

Osteitis  deformans'  is  adisease  of  unknown  origin,  usually  occurring 
after  middle  life  and  manifested  by  great  thickening  of  the  skull  and  the 
long  bones  with  marked  softening  and  proportionately  diminished 
resistance  to  pressure.  The  Haversian  canals  are  enlarged,  the  contents 
cellular,  and  the  new  bone  formed  on  the  periphery  of  the  old  is  also 
.  architectural! V  imperfect.  Much  of  the  new  osseous  growth  remains 
uncalcified.  The  cranium  is  broadened,  the  femur  is  curved  outward, 
and  the  tibia  is  arched  anteriorly;  the  bones  of  the  forearm  bend  toward 

'Vincent  Th^se  de  Paris.  1004-  Sonnebrrg.  Inaug.  Diss..  Leipzig.  1004. 
Willard  and  Andnis.  "Medicine."  1905.  p.  59  Shattuck.  "Boston  Med.  and 
Surg.  Jour.,"  Jan.  12.  1905,  p.  43- 


8i6 


SPECIAL    PATHOLOGV. 


the  dorsal  aspect,  and  the  clavicles  thicken  and  may  be  curved.     In 
Sommer's  case  the  ribs  were  widened.     It  is  not  universally  agreed  that 


i„ 


Fig.  399. — Exterior  of  Femur,  Showing  Result  of 
Chronic  Osteitis  Associated  with  Chronic 
Productive  Periostitis. 

The  growth  of  osteophytes  over  its  surface  is  well  ex- 
hibited. The  bone  also  shows  the  usual  deform- 
ity — great  thickening,  irregularity, — and  presents 
the  marked  density  with  which  these  conditions  are 
commonly  associated. 


Fig.  400 — Femur.  Longitudinal  Section  of  Bone 
Shown  in  Figure  399. 

It  will  be  observed  that  the  lesion  is  restricted  to  about 
two-thirds  of  the  bone.  The  marrow  cavity  has 
been  obliterated  by  the  progressive  osteosclerosis. 
The  induration  of  the  bone  was  such  as  to  require 
the  use  of  a  lapidary's  saw  for  making  the  section. 


the  process  is  inflaminatory ;    some  believe  that  it  is  trophic;    Fournier 
thinks  it  is  a  manifestation  of  syphilis. 


HONKS     A.\I>    JOINTS.  817 

Tuberculosis'  of  bone  may  bt-  iiianiffsted  as  an  acute  niiliarv  process 
constitutinji  a  part  of  a  general  liematoj^enous  (miliary)  infection.  In 
this  form  it  is  sometimes  termed  acute  tuberculous  osteomyelitis.  The 
miliary  tubercles  disseminated  throu!.,'h  the  bone  iikhiow  histoio^'icallv 
resemble  the  same  ]>rocess  occurring  elsewhere.  The  n;ost  frequent 
form  of  osseous  tuberculosis  is  chronic  in  character,  and  is  the  commonest 
of  all  diseases  of  llu-  bones.  The  lesion  produced,  commonlv  known  as 
chronic  tuberculosis  of  bone,  may  begin  in  the  i)eriosteum,  bone-marrow, 
synarthrosis,  epiphyseal  disc,  or  epiphysis.  The  bacilli  most  frefjuently 
reach  the  bone  through  the  circulation.  Lexer,  Konig,  and  others, 
have  shown  that  tuberculosis  of  bone  arises  as  a  result  of  a  tuberculous 
infarct,  and  Mliller  produced  such  a  process  by  the  intravascular  injec- 
tion of  tubercle  bacilli.  Invasion  may  also  occur  from  infection  of  con- 
tiguous structures,  and  possibly  through  the  lymphatics.  The  lesion  is 
most  fre(iuently  located  in  or  near  the  epiphyses,  through  involvement 
of  which  extension  to  the  adjacent  joint  commonly  occurs,  constituting 
the  usual  source  of  tuberculous  arthritis.  As  a  result  of  proliferation  of 
the  fixed  connective-tissue  cells,  as  well  as  of  leukocytic  invasion,  and 
more  or  less  effort  at  peripheral  vascularization,  the  formation  of  granu- 
lation tissue  is  brought  about.  Absorption  of  the  adjacent  bone  pro- 
gresses with  advance  of  the  tuberculous  new-formation  ;  Rutizkv, 
Ribbert,  and  others  believe  that  osteoclasts  are  not  necessar\-  to  the 
absorption  of  bone  in  the  presence  of  granulation  tissue.  Certainly, 
along  the  lines  of  osseous  invasion  in  tuberculosis  there  is  evidence 
clearly  indicating  that  decalcification  and  removal  of  the  bone  matrix 
without  the  presence  of  osteoclasts  are  in  progress.  In  rare  instances 
the  process  becomes  quiescent,  with  condensation  of  the  surrounding 
tissue,  constituting  a  form  of  healing-in  closely  allied  to  that  alreadv 
described  on  page  151.  Early  in  the  process,  as  a  result  of  the  specific 
poison  produced  by  the  tubercle  bacillus,  marked  changes  occur  in  the 
newly  formed  vessels,  followed  by  caseation  beginning  at  or  near  the 
center  of  the  diseased  area.  Such  caseous  areas  increase  in  size  bv 
confluence  of  adjacent  masses,  extension  into  and  absorption  of  the 
surrounding  bone,  and  eventually,  in  many  cases,  jierforation  of  the 
periosteum,  and  the  induction  of  a  paraosteal  tuberculosis,  therebv 
inducing  what  is  often  called  a  cold  abscess  ;  the  manifestation  in  this 
form  is  usually  observed  in  connection  with  tuberculosis  of  the  hi]) 
(coxalgia),  knee  (tumor  albus,  or  white  swelling),  vertebra?  (Pott's 
disease),  etc.  Necrosis  of  relatively  large  parts  tjf  the  affected  bone 
sometimes  occurs.  The  necrotic  mass  most  frequently,  although  not 
always,  involves  the  whole  or  a  part  of  the  ejiiphysis.  Destruction  of 
the  adjacent  bone  anri  invasion  of  the  articular  surface  and  joint  are 
often  observed,  destroying  the  function  of  these  structures.  As  a 
result  of  the  destruction,  erosion,  or  softening  of  the  bone,  distortion 
and  deformity  commonly  occur.  A  notable  example  of  deformity 
arising  from  this  cause  is  seen  in  the  spinal  column,  where  softening  of 
the  bodies  of  the  vertebrjp  gives  rise  to  posterior  arching  or  angular 
displacement  (kyphosis).  When  the  articular  surface  is  reached,  its 
destruction   is   almost  inevitable,   and,   under  the   most  favorable   cir- 

'  Moret.  Thtise  de  Paris.  1904.  Lexer.  "Arch.  f.  klin.  Chir.,"  1003.  Bd.  I.xxi, 
H.  I.     Hehlc.    "Wien.  klin.  Woch.,"     Sept.  22.  1904,  p,  loir. 

5.? 


8i8 


SPECIAL    PATHOLOGY. 


cumstances,  there  is  probably  nothing  better  to  be  expected  than  per- 
manent ankylosis  in  the  joint  so  affected. 

Even  in  its  most  chronic  form  tuberculosis  of  bone  presents  at 
least  two  distinct  dangers:  (i)  As  in  the  septic  osteomyelitis  already 
described,  general  dissemination  of  the  microbe  may  occur;  in  the 
former  condition  the  result  is  septicemia  or  pyemia,  and  in  the  disease 
under  consideration  acute  miliary  tuberculosis  is  produced.  In  other 
cases  the  secondary  manifestations  may  be  restricted  to  the  lungs.  (2) 
Infection  by  pyogenic  bacteria  adds  danger  by  augmenting  the  toxicity 
of  the  absorbed  poison,  or,  rather,  by  adding  new  absorbable  bodies, 
increasing  the  rapidity  of  the  osseous  destruction  and  rendering  less 
efficient  the  protective  and  recuperative  powers  of  the  patient. 

Syphilis  of  bone,  as  in 
other  tissues,  induces  a 
number  of  lesions,  many 
of  which  are  so  dissimilar 
as  to  render  it  quite  im- 
possible to  establish  any 
characteristic  relation  be- 
tween them.  Some  of  the 
lesions  of  syphilis  are  prob- 
ably due  to  lessened  resist- 
ance on  the  part  of  the 
economy,  giving  rise  to  the 
occurrence  of  bacterial  in- 
fections that  of  themselves 
induce  changes  in  nowise 
syphilitic. 

In  congenital  syphilis 
the  bones  at  birth,  or 
shortly  afterward,  show 
quite  characteristic  alter- 
ations at  or  near  the  epi- 
physeal line.  Such  changes 
are  best  exhibited  in  a 
longitudinal  section  of  the 
lower  end  of  the  femur. 
The  epiphyseal  line  is 
broadened  and  somewhat 
irregular,  the  irregularity 
being  more  marked  on  the  articular  side  than  toward  its  apophysis. 
Calcification  in  the  neighboring  areas  is  irregular,  and  proliferative 
changes  in  the  adjacent  bone  and  perichondrium  (syphilitic  osteochond- 
ritis) or  periosteum  occur,  sometimes  inducing  a  slight  thickening, 
which,  in  advanced  cases, may  even  resemble  rickets.  In  other  instances 
the  irregular  epiphyseal  line  assumes  a  grayish  or  bluish-white  hue  that, 
with  the  beginning  of  fatty  changes,  becomes  faintly  yellow.  Spontane- 
ous separation  of  the  epiphysis  (epiphyseolysis)  may  occur,  but  is  infre- 
quent.    The  epiphysis  is  usually  easily  detached. 

Histologically,  irregular  proliferation  of  the  cartilage  cells  can  be 
recognized,  with  an  associated,  unevenly  distributed  calcification,  and, 
later,  fattv  degeneration  in  the  newly  formed  elements.     The  prolifera- 


FiG.  401  — Femur,  Head  and  Neck;  Beginning  Tuberculosis. 

A.  Small  area  of  caseation  in  epiphysis  just  under  articular  carti- 
lage, called  subchondral.  5,  B.  Same  in  epiphyses  at  point  of 
junction  with  shaft;  intraosseous.  C.  Subperiosteal.  (After 
McArdle  (redrawn)  "Trans.  Royal  Acad,  of  Med.  in  Ireland," 
vol.  vii,  1889,  p.  140.) 


BOXES    A\n    JOINTS.  S  i  i; 

live  chanijes  in  the  periosteum  and  perichondrium,  previously  relerred 
to,  with  the  associated  enhirt;ement,  have  led  some  observers  U)  rej^ard 
such  alterations  as  manifestations  of  associated  syi>hilis  and  rickets, 
and  may  have  been  resi)onsible  for  the  belief  that  rickets  is  truly  an 
evidence  of  syphilis — a  view  that  has  now  been  discarded. 

Aiiiidrcd  syphilis  induces  no  conspicuous  bone  lesion  prior  to  the 
ajipearance  of  the  tertiary  stage.  During  the  secondary  stage  there  is 
probably  some  disturbance  of  the  marrow,  in  common  with  the  evident 
hyperplasia  of  other  blood-making  tissues,  notably  the  lymph-nodes 
and  spleen.  In  acquired  syphilis,  gummata  develop  most  commonly  in 
the  periosteum;  rarely  as  central  lesions.  Structurally,  they  do  not 
differ  from  gummata  occurring  elsewhere.  Degenerative  and  necrotic 
processes  involving  the  gumma  and  extending  to  the  overlying  tissue 
may  lead  to  external  evacuation,  followed  by  pyogenic  infection. 
Rarely,  pyogenic  infection  precedes  the  mucous  or  hyaline  degenerative 
change  observed  in  the  syphiloma.  Caseation  sometimes  occurs. 
Under  appropriate  treatment,  and  even  without  medication,  more  or 
less  absorption  may  take  place,  which,  associated  with  an  osseous  over- 
growth, gives  rise  to  osteophytic  enlargement,  irregularities  of  the  sur- 
face, osteosclerosis,  etc.  (See  Fibrous  Periostitis,  p.  804,  and  Chronic 
Osteitis.  ]).  815;   also  Figs.  399  and  400,  p.  816.) 

Actinomycosis  of  bone  is  rare  in  man;  when  present,  the  bones 
usually  involved  are  the  jaw,  bodies  of  the  vertebrae ,  ribs,  or  sternum. 
Occurring  in  the  jaw,  infection  probably  takes  place  through  a  tooth  or 
tooth-socket.  While  the  proliferative  and  necrotic  changes  of  actinomy- 
cosis are  in  progress  in  the  center  of  the  bone,  associated  with  resorption 
of  the  adjacent  osseous  tissue,  subperiosteal  apposition  not  infrequently 
occurs,  thereby  increasing  the  size  of  the  bone.  Suppuration,  resulting 
from  the  activity  of  the  fungus  or  from  concurrent  infection  by  pyogenic 
organisms,  commonly  occurs.  The  teeth  loosen  and  often  fall  out. 
The  tissue  necrosis  may  extend  through  the  oral  mucosa;  less  frequently 
an  external  opening  is  formed.  The  discharge  commonly  contains  the 
fungus,  which  can  usually  be  demonstrated,  except  when  late  secondary 
or  mixed  infection  produces  such  an  excess  of  pus  as  to  render  the  fungus 
difficult  to  find.  (For  Demonstration  of  the  Fungus  see  page  167.) 
Encapsulation,  similar  to  that  observed  in  tuberculosis,  is  infrequent, 
and  the  disease  rarely,  if  ever,  assumes  a  quiescent  stage. 

Leprosy  of  the  bone  is  manifested  occasionally  as  distinct  leprous 
nodules  occurring  in  the  medulla,  and  may  closely  resemble  tuberculosis. 
Xecrosis  and  more  or  less  active  inflammatory  ])rocesses  are  occasionally 
j)rescnt.  particularly  in  the  digits. 

Glanders  sometimes  attacks  a  bone.  Usually,  it  is  the  periosteum 
that  suffers,  except  in  the  septicemic  form  of  the  disease,  when  micro- 
organismal  invasion  of  the  medulla  may  occur. 

Fractures. — The  term  fracture  is  applied  to  solutions  in  the  con- 
tinuity of  l)one  or  cartilage.  This  definition  includes  separation  of  the 
epiphysis,  which,  surgically,  is  grouj)ed  with  fractures. 

Canscs. — Certain  factors  are  recognized  as  predisposing;  for  example, 
the  position  and  function  of  bones  as  well  as  their  shape  and  structure. 
Round  bones  are  less  liable  to  fracture  than  the  long  and  flat  bones, 
and  the  long  bones  of  the  extremities  are  more  subject  to  injur\',  and 
hence   are   more   frequently   fractured,   than   the   bones   of   the   trunk. 


820  SPECIAL    PATHOLOGY. 

Atrophic  processes  and  diseases  associated  with  rarefaction,  increase  the 
fragility,  and  hence  favor  the  occurrence  of  fracture.  The  bones  are  also 
weakened  by  rickets;  by  cellular  tumors  that  invade  the  marrow;  bv 
chronic  infections,  such  as  syphilis;  by  tuberculosis  under  certain 
circumstances;  and  by  other  diseases  similarly  influencing  the  density 
or  chemistry  of  the  bone. 

The  exciting  cause  is  nearly  always  violence.  This  may  be  direct, 
as  blows  upon  the  bones,  or  indirect,  as  when  the  clavicle  is  fractured  by 
a  fall,  the  force  having  been  transmitted  to  the  injured  bone  through 
the  bones  of  the  arm  and  hand ;  in  a  similar  way  the  base  of  the  skull  is 
sometimes  fractured  as  a  result  of  a  fall,  the  individual  landing  upon  the 
feet  or  in  a  sitting  posture.  Fractures  resulting  from  muscular  action  are 
typified  in  the  fracture  of  the  patella  occurring  during  the  act  of  kicking. 
Fractures  resulting  directly  from  disease  are  sometimes  spoken  of  as 
pathologic. 

The  lijic  of  fracture  may  be  transverse,  oblique,  longitudinal,  or  spiral; 
it  may  be  regular  or  irregular.  It  may  traverse  the  bone  in  one  direction, 
constituting  a  complete  fracture,  or  it  may  be  a  fissure,  not  extending 
through.  Bending,  with  fracture  on  one  side  {grcenstick  fracture),  occurs 
in  young  bone.  Detachment  of  bony  prominences,  such  as  the  mal- 
leolus or  trochanter,  is  sometimes  observed.  In  the  skull,  fracture 
associated  with  inward  displacement  of  a  fragment  is  called  a  depressed 
fracture.  When  the  bone  at  one  point  is  broken  into  a  number  of  frag- 
ments, the  fracture  is  said  to  be  comminuted;  when  broken  in  a  number 
of  places,  or  when  a  number  of  bones  are  broken,  the  fractures  are  said 
to  be  mtiltiple.  A  fracture  communicating  with  the  external  air  through 
a  wound  in  the  skin  or  mucosa  is  said  to  be  compound .  Certain  con- 
current conditions  constitute  complications,  and  such  fractures  are 
spoken  of  as  complicated  fractures.  Associated  injury  of  nerves  or  vessels 
and  extension  of  a  fracture  into  the  joint  are  examples  of  immediate 
complications;  sepsis,  faulty  or  imperfect  union,  and  tumor  formation 
at  the  point  of  fracture  constitute  remote  or  secondary  complications. 

As  a  rule,  the  fragments  of  the  fractured  bone  do  not  immediately 
resume  their  normal  relation  one  to  another,  and  hence  deformity 
occurs.  One  or  both  fragments  may  show  longitudinal  rotation  {rotary 
deformity)  in  different  directions  or  to  different  degrees  in  the  same 
direction.  Bending  at  the  point  of  fracture  {angidar  deformity)  is 
frequently  present.  Lateral  displacement,  overlapping,  and  separation 
of  the  fragments  are  not  infrequent.  The  rapidity  and  completeness  of 
the  reparative  process  are  favored  by  an  accurate  coaptation  of  the 
fragments.  That  this,  however,  is  not  absolutely  necessary  is  indicated 
by  figure  402. 

Repair  of  Bone.^ — Immediately  following  the  injury  an  abundant 
extravasation  of  blood  occurs;  this  collects  around  the  fragments, 
between  the  ends  of  the  compp,ct  portion  of  the  bone,  and  invades,  to  a 
certain  extent,  the  marrow.  Following  the  hemorrhage  the  initial 
hyperemia  of  repair  begins.  This  hvperemia  is  most  marked  in  the 
periosteum  and  adjacent  marrow,  although  all  the  surrounding  tissues 
show  it  to  a  moderate  degree.  From  the  hyperemic  areas  leukocytic 
infiltration  takes  place — the  leukocytes  removing  the  cellular  detritus 

'  Kraft,  "Ziesrler's  Beitr.,"  vol.  i,  p.  85.  Grohe,  "Arch.  f.  klin.  Chir.."  1904, 
Bd.  72,  H.  3.     Matsuoka,  "Virchow's  Arch.,"  1904.  Bd.  175,  p.  32. 


BONHS     AM)    JOINTS. 


821 


rcsultiU}.,'  Iroin  ihc  (k'StructiDn  of  lissuc  and  the  d:sintej.,'ratioii  ol  tlu- 
extruded  erythrocytes.  Within  from  forty-eight — according  to  Kraft, 
inside  of  forty-eight  hours — to  seventy-two  hours  after  the  injury  pro- 
Hferative  changes  take  ])hice  in  the  connective-tissue  cells,  ])articularly 
those  of  the  periosteum  and  the  bone-marrow,  although  similar  evidences 
f)f  cell  activity  are  to  be  rccognizefl  in  the  endo- 
thelium of  the  capillaries.  This  forms  the  ger- 
y  minal  or  reparative  tissue,  certain  cells  of  which 

^  (iliroiuirohlast.s)  arise  from  the  genetic  layer  of  the 

^  periosteum  and  from  the  medullary  cavity  and 

produce  a  matrix  of  temporary  cartilage;  from 
the  same  tissues  are  produced  other  cells,  the 
function  of  which,  later,  is  the  completion  of  os- 
seous formation ;  these  are  called  ostcobhists.  The 
mass  of  new  tissue  is  known  as  chondroid  or  os- 
teoid tissue,  and  constitutes  what  clinicians  call 
callus.  Structurally,  the  callus  is  more  or  less 
uniform,  but  its  position  has  led  to  a  descri])tion 
of  three  different  parts:  The  external,  circumfer- 
ential, encircling,  or  ensheathing  callus  is  that 
surrounding  the  bone;  the  internal,  medullar)', 


'If 


Fig.      432. — FRAfTI-RK      OF       THK 

Fkmcr,  Siiuwino  Over- 
lapping OF  THK  FrACMKNTS 
WITH  Rotatory  UispI-ACE- 
MKNT  or  the  I.OWER  Frac- 
MKNT,  AND  .\TTKMPTED 
I   NIoN  I.V  THIS   I'O-ilTION. 


■fj^* 


Fig.  403. — Ten-day-old  Fractvre.— (5'-Amauj.) 
m.  m.  UoncmaiTow.     P,  P.   I'jirtly  dctachc-d  (icriostcuni.     t",  C',  C  Uclxjsit 
(if  ostt-oiil  .infl  (h(in(lr<>i<l  tissuo  umicr  ihc  fxTi(»lrum  rind  oxtrniline  lic- 
iwet-n  the  ends  of  the  two  Innmenis  and  into  the  mctlulla— the  callus. 


or  pin  callus  occupies  the  central  canal  of  the  two  fragments;  while  the 
callus  between  the  compact  ])ortion  of  the  two  ends  is  called  the  intermedi- 
arv  or  ring  callus.  The  matrix  produced  by  the  chondroblasts  is  essentially 
a  cartilaginous  or  chondroid  tissue ;  it  is  at  least  a  ])roduct  of,  if  not  a  part 
of.  their  cvtoplasm,  and  is  shortly  transformed  into  a  marrow-like  struc- 


822  SPECIAL    PATHOLOGY. 

ture  bv  the  entrance  of  young  blood-vessels.  The  latter  are  produced  by 
budding  projections  from  the  nearest  vascular  twigs.  (See  Development 
of  New  Blood-vessels,  p.  304.)  The  final  step  in  bone  production  consists 
in  calcification  of  the  osteoid  matrix.  New  marrow  is  formed  by  the 
projection  of  blood-vessels  bringing  with  them  a  mantle  of  marrow- 
cells.  From  these,  and  possibly  from  the  proliferation  of  adjacent  cells 
with  the  abundant  growth  of  new  blood-vessels,  the  marrow  cavity  is 
reestablished. 

Absorption  of  irregular  and  useless  spicula  begins  early  in  the 
process,  and  is  carried  on  by  the  leukocytes  and  osteoclasts  already 
mentioned.  After  a  time,  varving  in  different  cases,  removal  of  the 
ensheathing  or  temporary  callus  takes  place.  This  is  accomphshed 
through  the  intervention  of  the  osteoclasts  and  chondroclasts,  and 
requires,  not  uncommonly,  many  months  for  its  completion.  Wide 
separation  of  fragments,"  defective  immobihzation,  the  presence  of 
muscle  or  other  soft  tissue  between  the  fragments,  and  inherent  deficient 
reparative  power  on  the  part  of  the  tissues  may  prevent  complete 
union. ^  The  degree  of  faulty  union  varies.  Sometimes  after  weeks 
there  has  been  no  perceptible  effort  at  repair;  in  other  cases  fibrous 
tissue  firmly  joins  the  two  ends,  constituting  fibrous  union,  which  later, 
with  rounding-off  of  the  ends  of  the  bone,  terminates  in  the  formation  of 
a  false  joint  {pseudarthrosis).  Excessive  callus-formation  may  lead  to 
the  coalescence  of  the  reparative  tissues  arising  from  fractures  of  parallel 
bones  at  the  same  level,  and,  later,  may  firmly  unite  all  the  fragments, 
constituting  a  svnostosis. 

Rickets^  ;  Rachitis  ;  Rachitismus  ;  Morbus  Anglicus. — Rickets  is  a 
disorder  of  nutrition  in  which  the  process  of  growth  in  the  bones,  muscles, 
mucous  membranes,  and  many  other  tissues  is  profoundly  influenced. 
The  disease  is  not  primarily  one  of  bone.  The  changes  seen  in  the  bones 
are  dependent  upon  defective  nutrition  during  the  period  of  most 
active  osseous  growth. 

Etiology. — Rickets  is  a  disease  of  childhood,  usually  developing  toward 
the  end  of  the  first  year,  and  nearly  always  before  the  end  of  the  second 
or  third  year,  although  rare  instances  are  reported  in  which  the  disease 
showed  its  first  manifestations  as  late  as  the  ninth  year.  Neither 
syphilis,  unsanitary  surroundings,  disorders  of  the  digestion,  nor  hered- 
ity are  sufficient  causes,  although,  with  the  exception  of  the  last  named, 
they  may  intensify  the  activity  of  the  process.  As  the  disease  is  not  re- 
stricted to  the  human  family,  but  also  occurs  in  monkeys  and  in  Hons' 
whelps,  certain  experimental  observations  have  been  made.  The 
experiments  of  Cheadle  and  Bland-Sutton  seem  to  indicate  that,  at 
least  in  lions,  the  morbid  condition  may  be  avoided  by  the  use  of  a  diet 
rich  in  cream,  proteids,  and  earthy  phosphates.  The  necessity  for  fat  in 
the  diet  seems  to  be  thoroughly  established,  and  the  fact  that  children 
become  rickety  on  a  diet  containing  fat  is  presumed  to  depend  upon  the 
presence  of  associated  digestive  disturbances  that  prevent  the  emulsi- 
'  For  recent  studies  on  conditions  causing  non-union  or  malicious  union,  see 
Comil  and  Coudrav,  "Revue  de  Chir.,"  July,  1904.  _^ 

^Sinnhuber  "Zeit.  f.  klin.  Med.,"  Bd.  54,  Nos.  i  and  2.  SpiUman.  Arch, 
de  Med.  des  Enfants,"  May,  1901.  Edlessen,  Kassowitz  and  others,  "Centralbl. 
f.  inn.  Med.,"  Sept.  6,  1902.  Pfaundler,  "Jahrbuch.  f.  Kinderheilk.,"  1904,  Bd. 
60.  Nathan,  "Med.  News,"  Feb.  20,  1904,  p.  391.  Freeman,  "Arch,  of  Pediatrics," 
April,  1904. 


BONES     AND    JOINTS.  82.? 

fication  and  (.onsequent  absorption  of  this  body;  therefore  changes  in 
the  diet  after  the  occurrence  of  catarrhal  i)rocesses  in  the  ahmentary 
canal  often  fail  to  modify  the  disease.  The  beliefs  that  it  is  an  infection 
(Edlessen),  an  intoxication  (Kassowitz),  and  that  it  de])ends  ujjon  dis- 
ease of  the  thymus  (Memlcl)  rest  upon  evidence  which  is  not  conclusive. 
There  is  a  ijeneral  conviction  that  it  depends  upon  dietetic  errors  or 
digestive  disturbances,  but  exactly  how  these  factors  operate  remains 
undetermined. 

Morbid  Anatomy.— \  conspicuous  and  usual  change  is  the  develoj)- 
ment  of  the  rachitic  rosary,  which  consists  of  an  enlargement  a])pearing 
at  the  junction  of  the  ribs  and  costal  cartilages,  usually  more  marked  on 
the  inner  than  on  the  external  surface,  and  commonly  cons])icuous  at 
the  junction  of  the  fifth  and  sixth  ribs  with  their  respective  cartilages. 
This  enlargement  has  been  recognized  in  the  fetal  skeleton,  and  is  some- 
times present  at  birth.  The  craiiiotahcs  of  Elsasser  consists  of  absorp- 
tion and  thinning  of  the  cranial  bones,  most  marked  in  the  ]jarietal 
and  occipital  regions.  The  marginal  membranous  portions  of  the  bone 
do  not  show  the  normal  progressive  ossification.  Associated  with  the 
absorption  of  the  inner  table  and  the  thinning,  there  also  occur  hyper- 
plastic changes,  swellings,  or  bosses  over  the  frontal,  parietal,  or  occipital 
bones.  The  sutures,  excepting  the  mediofrontal,  show  delayed  union, 
and  the  anterior  fontanel  often  remains  open  until  the  end  of  the 
second  year  or  even  later.  The  teeth  appear  late  and  frequently  not  in 
their  proper  order:  they  become  carious  early.  In  addition  to  the  ra- 
chitic rosary,  already  mentioned,  the  chest  shows  flattening  on  the  sides, 
and  the  sternum  is  thrust  forward  (piiicon-breast).  Posterior  and 
lateral  curvature  of  the  spine  occur.  The  iliac  crest  is  sometimes 
thickened  and  the  pubic  arch  may  be  narrowed.  Juxta-epiphyseal 
enlargements  similar  to  those  observed  on  the  ribs,  appear  in  the  long 
bones,  particularly  the  radius,  ulna,  tibia,  and  femur.  The  periosteum 
seems  more  vascular  than  normal,  and  strips  off  with  unusual  readiness. 
The  underlying  bone  is  commonly  soft,  and  frequently  bends;  green- 
stick  fractures  may  occur. 

Histologically,  there  is  evidence  of  "excessive  preparation  for  bone 
formation  which  does  not  occur"  (Jenner).  Osteoporosis,  depending 
upon  lacunar  absorption,  is  present.  Unusual  periosteal  production 
of  osteoid  tissue  gives  rise  to  osteophytes  that,  with  the  advent  of 
recovery,  are  converted  into  bone,  thus  perpetuating  the  deformity 
produced  by  their  growth.  The  line  of  calcification  in  the  juxta-epij)hy- 
seal  cartilage  is  irregular,  poorly  marked,  or  may  be  absent.  There  is  an 
abundant  production  of  osteoid  matrix,  into  which  medullary  vessels  are 
projected  without  the  usual  accompanying  deposit  of  bone. 

In  addition  to  the  osseous  changes  already  mentioned,  the  ligaments 
of  the  joints  are  lax  and  frequently  give  way.  The  muscles  usually 
show  deficient  and  imperfect  striation.  and  during  life  are  weak.  The 
liver  and  spleen  are  not  infrequently  enlarged,  and  commonly  show 
increase  in  fibrous  tissue.  More  or  less  evidence  of  associated  catarrhal 
inflammation  of  tlie  muco.sa>  is  usually  present. 

Tumors  of  Bone. — Primary  epithelial  neoplasms  do  not  occur  in 
normal  bone;  the  comj)lex  developmental  processes  occurring  in  the 
maxillae  are  sometimes  attended  by  the  presence  of  epithelial  vestiges 
from   which    carcinoma  occasionallv    arises.      Secondar\'  cancer  of   the 


824 


SPFXIAL    PATHOLOGY 


bones  may  be  due  to  direct  extension  or  to  lymphatic  involvement  of 
osseous  tissues  within  the  lymph  area  draining  a  primary  cancerous  focus. 
Herbert  Snow  has  particularly  investigated  this  question,  and,  although 
his  views  have  been  criticized,  appears  to  have  demonstrated  that 
cancerous  foci  may  lie  dormant  in  the  bone-marrow  for  months. 
When  active,  they  give  rise  to  rapid  absorption  of  bone,  softening,  and 
frequently  fractures.  Metastasis  of  th^^roid  tissue  to  bones  is  mentioned 
on  page  784.  Myxoma  of  bone  is  rare;  Soubeyran^  has  been  able  to 
collect  six  cases  of  pure  myxoma;  most  tumors  of  this  nature  are  myxo- 
sarcomata.  Katholitzky  has  recorded  an  instance  of  lymphangiomatous 
involvement  of  bone.  Angiomata  of  bone  have  been  described,  and 
extremely  vascular  masses  called  bone  aneurysms  sometimes  occur; 
Gaylord-  has  collated  the  reported  cases  of  the  latter  group  and  records 

an  original  observation;  he 
believes  such  masses  are  usu- 
ally sarcomatous.  Chondro- 
mata  are  not  infrequent 
tumors  of  bone;  they  de- 
velop from  the  periosteum 
or  the  epiphyseal  junctions 
and  are  generally  believed  to 
arise  from  vestiges  of  em- 
bryonal cartilage;  in  some 
cases  they  are  multiple.  Sar- 
coma originates  in  the  peri- 
osteum or  in  the  interior  of 
the  bone;  any  type  of  cell 
may  be  present;  giant-cell 
sarcomata  frequently  in- 
volve the  maxillae  and  are 
the  least  malignant.  Occa- 
sionally sarcoma  of  bones  is 
congenital;  tumors  of  this 
type  may  begin  in  the  me- 
dulla and  cause  extensive 
osseous  resorption  terminat- 
ing in  fracture  without  mani- 
festing any  external  evidences  of  their  presence;  they  sometimes 
follow  injury.  An  important  but  rather  infrequent  tumor  of  bone 
is  one  arising  in  the  marrow,  apparently  belonging  with  the  sarco- 
mata, and  known  as  the  myeloma^  ;  the  condition  is  also  called 
myelomatosis  and  Kahler's  disease.  The  affection  during  life  is  often 
diagnosed  osteomalacia.  In  one  type  of  the  morbid  process  the  bone 
alone  is  involved,  and  in  another  metastases  to  the  lymph-nodes  and 
other  structures  occur.  When  the  bodies  of  the  vertebrae  are  involved, 
kypho.sis  results.     The  cells  composing  the  tumor  are  round  or  poh^he- 


FiG.  404. — Sarcoma,  Mixed-cell  with  Calcification  of 
Part  of  the  Intercellular  Matrix;  Osteosarcoma. 

A.  Calcified  area  in  osteoid  matrix.  B.  Osteoid  tissue  wliich,  in 
some  areas,  gives  rise  to  an  alveolar  arrangement.  C-  Osteo- 
blastic cell. 


1  "Revue  de  Chir.,"  April  10,  1904,  p.  5S9. 

^  "Annals  of  Surgery,"  June,  1903,  p.  834. 

^  Vignard  and  Gallavardin,  "Revue  de  Chir.,"  Jan.  10,  1903.  Weber,  Hutch- 
i.son  and  Macleod,  "Amer.  Jour,  of  Med.  Sci.,"  Oct.,  1903.  Lindemann,  "Deut. 
Arch.  f.  klin.  Med.,"  1904,  Bd.  81.  Meltzer,  "Med.  Record,"  June  18,  1904,  p. 
9S9.     Jellinek,  "Virchow's  Arch.,"  1904,  Bd.  177,  p.  96. 


BONES    AND    JOINTS.  825 

dral,  and  resemble  the  ])lasma  cell  (p.  ,^0.3).  Usually  the  growth  de- 
velops primarily  in  the  marrow  of  the  vertebra;,  hbs,  and  sternum,  but 
eventuallv  affects  the  marrow  of  all  the  bones.  The  affection  is  also 
characterized  by  the  ])resence  in  the  urine  of  a  peculiar  proteid  called 
Hence-Jonos  albumin. 

Cysts  of  bone'  may  result  from  necrotic  and  licjuefactive  changes  in 
tumors  (p.  371),  occasionally  develop  from  embryonal  vestiges  (den- 
tigerous  cysts),  and  are  sometimes  due  to  parasites  (hydatid).  The 
osseous  system  is  rarely  the  seat  of  dermoid  cysts. 

THE  JOINTS. 

A  joint  IS  composed  of  the  articular  ends  of  two  or  more  bones;  of 
the  capsule,  ligaments,  or  other  structures  binding  the  bones  together 
and  retaining  them  in  their  proper  relations  one  to  the  other;  and  of  the 
svnovial  membrane,  the  function  of  which  is  to  lubricate  the  articulating 
surfaces.  The  ends  of  the  bones  entering  into  the  articulation  are 
commonly  covered  by  articular  cartilages,  and  may  be  further  protected 
bv  intermediary  structures  not  properly  belonging  to  either  bone.  The 
capsule  and  ligaments  are  composed  of  fibrous  tissue  more  or  less  rich  in 
elastic  elements,  dense  and  firm,  offering  certain  protection  to  the  joint 
and  resisting  intra-articular  accumulations.  The  synovial  or  serous 
membrane  of  the  joint  possesses  an  outer  layer  of  elastic  fibers  and 
tibrillar  ti.ssue.  continuous  with  that  of  the  adjacent  structures,  and  an 
exposed  stratum  of  flattened  endothelial  cells. 

Malpositions  and  malformations  of  the  joints  may  be  congenital  or 
ac(]uired.  The  congenital  malformations  are  usually  dependent  upon 
developmental  arrest,  or  abnormal  pressure  involving  particularly  the 
articular  surfaces,  and  are  manifested  by  such  deformities  as  club-foot, 
knock-knee,  club-hand,  etc.  The  acquired  malpositions  and  malfor- 
mations are  either  the  result  of  disease  that  more  or  less  profoundly 
alters  the  bone,  or  of  trauma,  relaxation  of  the  ligaments,  or  unusual  or 
abnormal  muscular  contraction  or  other  applied  force  leading  to  altered 
relations  between  the  articular  surfaces  and  constituting  a  lesion  called 
a  luxation,  or  dislocation. 

Fatty,  hyaline,  and  mucoid  degenerations  occur  in  the  synovial 
membrane,  and  occasionally  in  the  articular  cartilage.  The  hyaline 
material  mav  resemble  lardacein,  even  to  the  extent  of  yielding  the  ap- 
propriate reactions.  Fat  accumulates  in  the  synovial  fringes,  and 
later  the  >ame  mav  be  converted  into  cartilage  or  chondroid  substance. 

Metaplasia  of  the  cartilage  into  fibrous,  mucoid,  or  osteoid  tissue 
occasionally  occurs,  and  in  rare  instances  it  may  be,  in  part  at  least, 
converted  into  a  marrow-like  substance. 

Infiltrations  into  Joint  Structures. — Calcareous  iufiltration  not  in- 
fre(iuentlv  follows  rejiarative  processes  in  the  neighborhood  of  a  joint 
and  inflammations  of  the  joint  capsule  and  synovial  meniV)rane.  par- 
ticularly when  chronic,  and  also  occurs  as  a  result  of  chronic  infection, 
notablv  tuberculosis,  either  of  the  joint  or  of  an  adjacent  structure. 
The  condition  is  sometimes  noted  in  old  age  independent  of  evident  gross 
lesions  of  inflammation. 

'  Turner  "Edinburgh  Med.  Jour."  Nov.,  1003.  Beck.  "Arch.  f.  klin.  Chir." 
1003.  Bd.  l.\x,  H.  4.     Bloodgood,  "Jour.  Amer.  Med.  Assoc."  Oct.   15.  1004.  p. 

I  124- 


826  SPECIAL    PATHOLOGY. 

Hemorrhage  into  the  joint  (hemarthron)  or  into  any  structure  of  the 
joint  is  frequently  associated  with  the  presence  of  pi-gment  held  in  the 
matrix  of  the  cartilage  and  fibrous  tissue  as  well  as  in  the  capsule  of  the 
normal  cartilage  cell.  1  have  discussed  the  hemarthrosis  of  hemophilia 
on  page  263.  Reference  has  been  made  to  the  uratic  deposits  occurring 
in  the  cartilages  in  gout.     (See  p.  238.) 

Loose  Bodies  in  the  Joints. — These  are  occasionally  seen  in  the  joints 
of  the  elbow,  wrist,  hip,  shoulder,  and  ankle,  but  in  "from  eighty-live  to 
ninetv  per  cent,  of  the  cases  the  knee-joint  is  affected.  Their  presence 
in  arthritis  deformans  will  be  referred  to  when  discussing  that  affection. 
They  mav  result  from  detachment  of  the  articular  cartilage,  or  may 
consist  of' a  fragment  of  bone  or  synovial  fringe  that  has  become  cartil- 
aginous, fibrous,  or  hpomatous,  or  they  may  be  produced  by  the  exfolia- 
tion of  fibrinous,  calcareous,  or  inflammatory  masses.  Loose  bodies  are 
usually  small  and  irregular,  rarely  attaining  the  size  of  two  or  three 
centirneters.  They  are  sometimes  multiple;  Thomson^  removed  a  pint 
of  loose  bodies  from  the  knee-joint.  The  structure  is  largely  dependent 
on  the  origin,  as  indicated  by  the  foregoing  hst  of  causes.  Occasionally, 
a  loose  body  may  be  attached. 

Inflammations  of  Joints.- — Theoretically,  it  is  possible  for  an  in- 
flammatory process  to  be  restricted  to  any  one  of  the  tissues  entering 
into  the  formation  of  the  joint,  or  it  may  involve  a  number  or  all  of  the 
articular  structures.  Inflammation  of  the  cartilage  is  called  articular 
chondritis ;  inflammation  of  the  synovial  membrane,  synovitis ;  in- 
flammation of  the  joint  capsule  and  ligaments,  parasynovitis  ;  while 
inflammatory  processes  involving  all  these  structures  are  grouped  under 
the  name  of  panarthritis.  Chronic  inflammatory  processes  or  inflam- 
mations of  a  low  grade  may  be  restricted  to  one  of  the  foregoing  struc- 
tures, but  joint  inflammations  are  rarely  simple  processes,  and  usually 
include  more  or  less  involvement  of  all  the  structures. 

Inflammation  is  sometimes  restricted  to  a  single  joint  (monarticular 
arthritis,  monarthritis),  or  a  number  of  joints  may  be  simultaneously 
affected,  or  in  quick  succession  (polyarticular  arthritis,  or  polyarthritis). 

Acute  simple  serous  synovitis  is  an  inflammatory  process  not  due  to 
pus-producing  organisms,  or  at  least  to  pyogenic  bacteria  of  such  viru- 
lence as  to  lead  to  the  accumulation  of  polymorphonuclear  leukocytes 
(pus) ;  whatever  the  cause  may  be,  it  gives  rise  to  a  more  or  less  abundant 
serous  or  synovial  accumulation  in  the  joint  cavity  or  adjacent  bursje, 
or  both. 

Etiology. — Such  injuries  as  contusion,  sprain,  pinching  of  the  synovial 
folds,  loosening  of  articular  cartilages,  and  loose  bodies  in  the  joints  may 
be  taken  as  types  of  the  purely  local  causes.  A  similar,  although  pos- 
sibly not  identical,  inflammatory  process  is  induced  by  the  presence  in 
the  "circulation  of  irritants,  either  bacterial  or  chemic  or  possibly  both. 
The  joint  inflammation  of  acute  rheumatism^  partakes  of  many  of  the 
characters  of  an  acute  serous  synovitis,  and  is  clearly  an  infection  (p. 
112).     The  inflammatory  process  in  gonorrhea  is  usually  associated  with 

^  "Lancet,"  March  16,  1901. 

^  Guyot,  "L' Arthritis  Maladie  generale,  Microbienne  et  Transmissible,"  2e  ed., 
Paris,  1905. 

3  Walker  and  Ryffel,  "Brit.  Med.  Jour.,"  Sept.  19,  1903,  p.  659.  Poynton. 
"Brit.  Med.  Jour.,"  May  14,  1904;   also  "Practitioner,"  June,  1904,  p.  864. 


BONES    AND    JOINTS.  827 

characters  of  an  acute  serous  synovitis,  and  is  clearly  an  infection  (]>. 
107).  The  gonococcus  commonly  causes  an  abundant  migration  and 
accumulation  of  polymorphonuclear  leukocytes,  and  hence  justly  the 
process  should  be  consitlered  with  the  sui)[)urative  form  of  arthritis, 
although  cases  essentially  serous  in  nature  do  occur. 

Morbid  Anatomy. — The  process  may  be  monarticular  or  polyarticular. 
It  is  most  frequent  in  the  large  joints  possessing  complicated  internal 
structures,  and  particularly  those  subjected  to  the  greatest  strain  an<l 
most  liable  to  injury.  Such  joints  are  those  of  the  knee,  ankle,  elbow, 
and  wrist.  The  initial  manifestations  are  usually  in  the  synovial  mem- 
brane. There  is  probably  at  lirst  a  scantiness  in  the  synovial  secretion, 
associated  with  hyperemia  of  the  membrane,  the  bright  red  surface  of 
which  contrasts  strongly  with  the  pearly-white  articular  cartilages. 
The  first  tiuid  extruded  is  usually  quite  clear,  but  later  is  cloudy  from 
the  addition  of  migrated  leukocytes  and  desquamated  endothelial  cells. 
Erythrocytes  are  occasionally  present,  particularly  in  the  earlier  stages. 
The  synovial  intiammation  partakes  of  all  the  characters  and  variations 
occurring  in  inflammation  of  serous  membranes,  and  hence  mav  be 
serous,  dry,  flbrinous,  or  serofibrinous.  (See  Inflammation  of  the  Serous 
Membranes,  p.  461.)  The  amount  of  fibrin  varies;  occasionally,  the 
disease  runs  its  course  wit^hout  the  presence  of  fibrin  in  the  fluid  evacu- 
ated by  operation.  On  the  other  hand,  extensive  fibrinous  deposits 
sometimes  occur,  and  these,  going  on  to  organization,  form  adhesions, 
thicken  the  synovial  membrane,  and,  with  added  connective-tissue 
elements  in  the  capsule  and  lessened  secretion,  terminate  in  a  form  of 
fibrous  ankylosis.  Ankylosis  is  more  likely  to  occur  in  the  dry  or  fiVjrin- 
ous  type  of  this  disea.se.  Occasionally,  a  serous  accumulation  ])ersists 
for  a  long  time  in  the  joint,  constituting  a  form  of  eft'usion  called  hydrops 
arthrosis.  In  the  dry  form,  and  occasionally  in  the  serous  form,  when 
associated  with  fibrinous  deposits,  loose  masses  of  fibrin  are  found ; 
sometimes  these  are  attached  to  the  long,  thread-like  fimbriae  of  the 
synovial  membrane.  Under  more  favorable  conditions  the  serum  is 
often  absorbed,  the  fibrin,  if  small  in  amount,  liquefies  and  is  removed 
by  the  vessels  and  lymphatics,  and  the  joint  returns  to  the  normal; 
subsequently,  such  joints  usually  possess  a  rather  high  degree  of  sus- 
ceptibility to  irritation. 

Acute  Suppurative  or  Purulent  Arthritis.' — As  elsewhere,  suppuration 
within  a  joint  can  be  produced  by  the  injection  of  purely  chemic  bodies: 
that  it  is  ever  engendered  in  this  way,  except  experimentally,  does  not 
seem  probable.  Infection  by  any  of  the  pyogenic  bacteria  may  give  rise 
to  a  suppurative  arthritis;  as  causes,  the  pyococci  should  be  first  men- 
tioned; the  gonococcus,  pneumococcus.  Bacillus  coli  communis,  typhoid 
bacillus,  and  occasionally  other  organisms,  may  induce  a  purulent 
arthritis.  The  infection  sometimes  reaches  the  joint  through  a  wound 
communicating  with  the  surface.  In  other  cases  a  peri-articular 
suppurative  process  involves  the  articular  structures.  Occa.sionally. 
suppurative  foci  in  or  near  the  articular  end  of  the  bone  penetrate  the 
joint.  (See  Fig.  398,  p.  813.)  In  other  cases  the  joint  is  infected 
through  the  blood;  as  examples  of  hematogenous  infection  may 
be   cited    suppurative  forms  of   gonorrheal  rheumatism,  and  the  joint 

'  Marsh.  "Brit.  Med.  Jour.,"  Dec.  13.  1002.  p.  1831.  von  Bruns.  "Berl.  klin. 
Woch.  '  July  4,  1904.      Ta.shiro.  "Zicgler's  Beitr.."  1003.  Bd.  34,  p.  540. 


828  SPECIAL    PATHOLOGY. 

complications  of  pnetimonia,  septicemia,  pyemia,  typhoid  and  puer- 
peral sepsis. 

Morbid  Anatomy. — Like  the  acute  simple  form,  the  disease  may  be 
monarticular  or  polyarticular.  While  it  is  not  improbable  that  the 
affection  begins  as  a  synovitis,  in  a  large  number  of  cases  it  quickly 
becomes  a  panarthritis. "  The  initial  stage  of  the  process  closely  resembles 
that  observed  in  the  acute  serous  synovitis.  The  hyperemia  is  usually 
more  marked  and  the  leukocytic  migration  far  in  excess  of  that  usually 
seen  in  the  synovial  inflammation  described.  In  the  latter  condition 
the  hyahne  cell  is  usually  most  abundant,  while  in  the  suppurative 
form  "the  polvmorphonuclear  is  the  predominating  leukocyte.  The 
distention  of  'the  joint  may  be  marked.  Erosions  in  the  cartilage 
occur,  sometimes  associated  with  exfoliations  (necrosis)  of  considerable 
size.  Occasionally,  the  whole  epiphysis  may  be  detached,  particularly 
when  the  original'focus  was  in  the  bone.  Necrotic  spots  appear  in  the 
joint  capsule;  these,  when  extensive,  lead  to  its  disintegration,  with- 
drawing the  normal  support  of  the  joint  and  permitting  luxation  {patho- 
logic luxation);  later,  peri-articular  suppuration  is  induced,  which  often 
involves  the  adjacent  tendons,  tendon-sheaths,  and  bursae,  burrowing 
along  the  course  of  such  structures  or  presenting  at  the  surface  as  a  peri- 
articular  abscess.  The  extent  of  damage  to  the  joint  is  largely  depen- 
dent upon  the  activity  of  the  process,  but  more  particularly  upon  the 
length  of  time  it  is  allowed  to  progress  without  evacuation  of  the  in- 
flammatory accumulation.  The  early  withdrawal  of  the  infection  favors 
the  progress  of  repair;  if,  however,  it  be  permitted  to  persist,  erosion 
of  the  articular  ends  of  the  bone  occurs,  with  the  destruction  of  the 
synovial  membrane  and  joint  capsule,  leaving  Httle  better  to  be  hoped 
for  than  a  more  or  less  firm  fibrous  ankylosis  in  which  extensive  cal- 
careous infiltration  takes  place,  resulting  in  what  is  practically  a  bony 
ankvlosis. 

Gouty  Arthritis.^ — The  articular  inflammation  occurring  in  gout  is  in 
part  a  serous  svnovitis  associated  with  the  precipitation  of  sodium 
biurate  upon  and  in  the  articular  cartilages,  and  also,  although  not  to  the 
same  extent,  in  the  joint  capsule  and  hgaments  and  synovial  membrane, 
and  occasionally  in  the  peri-articular  structures  as  well.  Late  in  the 
process  the  peri-articular  deposit  is  constant.  The  acicular  crystals  are 
deposited  in  the  cartilaginous  matrix  and  in  the  capsules  of  the  cartilage 
cells,  as  well  as  upon  the  free  surface.  The  cartilage  near  and  upon  the 
adjacent  bone  usually  escapes.  The  deposit  may  occur  in  normal 
cartilage,  and  the  late  degenerative  processes,  terminating  in  erosion, 
exfoliation,  or  necrosis,  are  truly  secondary  to  the  irritation  of  the  urate 
present.  From  the  experiments  of  Garrod  and  from  other  studies  it 
would  appear  that  the  uratic  infiltration  comes  from  the  synovia  rather 
than  from  the  osseous  or  cartilaginous  tissues  themselves. 

That  the  synovial  membrane  is  not  the  tissue  essentially  at  fault 
is  shown  by  the  fact  that  deposits  also  occur  in  the  eyehd,  ear,  and  nose. 
The  clinical  notes  justify  the  belief  that  the  deposits  occur  only  before 
and  during  a  paroxvsm.  Associated  with  the  infiltration  by  the  biurate, 
or  probably  secondary  to  the  necrosis  that  accompanies  it,  deposition 

*  Sympositim  on  Gout,  "Practitioner,"  July,  1903,  pp.  i  to  106.  Futcher. 
"Jour.'Amer.  Med.  Assoc,"  Nov.  26,  1904,  p.  1507.  Rosenbach,  "Virchow's 
Arch.,"  1905,  Bd.  179,  p.  359- 


HONKS    AND    jdlNTS.  829 

ot  calcium  carbonate  ami  iihosphalc  also  takes  place.  These  sometimes 
induce  peri-articular  enlarj,'enient,  constitutinjj  the  so-called  tophi. 
The  ^outy  inflammation  is  most  frequent  in  the  metatarsophalanj^eal 
joint  of  the  ^reat  toe.  When  the  deposit  reaches  the  surface,  infection 
followed  by  supjutration  occasionally  ensues.  The  discharj^e  ccnnmonly 
contains  the  needle-like  crystals  of  sodium  biurate.  (See  Urii-  Acid 
Deposits,  p.   2_vS. ) 

Osteoarthritis';  clu\'nic  arthritis:  arthritis  dcfornuDis;  rhcunuitoid 
arthritis;  dry  arthritis:  trophic  arthritis:  spondylitis  dcjoruians  (vertebra?), 
are  all  synonyms  indicating,'  the  protean  manifestations  of  the  disease, 
or  expressions  of  the  various  views  that  have  been  held  as  to  its  cause. 
The  etiology  of  the  affection  remains  undetermined;  it  has  been  suf(- 
gested  that  it  is  (i)  primarily  a  disease  of  the  nervous  system,  (2)  an 
infection.  Those  who  incline  toward  the  bacterial  origin  of  deforming 
arthritis  are  undecided  as  to  whether  it  is  a  specific  infection — due  to  a 
single  organism — or  can  be  produced  by  any  one  of  a  number  of  bacteria. 
The  suggestion  has  been  made  that  it  is  an  intoxication;  this  view, 
however,  has  not  been  regarded  with  favor.  Osteoarthritis  mav  be 
monarticular  or  polyarticular,  and  may,  in  certain  stages  of  its  evolution, 
resemble  acute  rheumatism  and  gout.  In  the  monarticular  form  the 
hip,  knee,  shoulder,  and  elbow  most  frequently  suffer.  The  polyarticular 
manifestation  is  a  disease  of  the  smaller  joints  of  the  extremities  and  of 
the  vertebra?  (spondylitis  deformans).  The  inception  of  the  disease 
frequently  occurs  earl\'  in  adult  life,  and  is  usually  preceded  bv 
trauma,  sometimes  by  rheumatism.  It  is  a  panarthritis,  usually  begin- 
ning in  the  synovial  membrane  or  in  articular  cartilages  by  ])roliferation 
of  the  cartilage  cells  and,  later,  leading  to  the  formation  of  a  superficial 
fibrillated  matrix;  as  the  fibrillation  is  particularly  marked  on  the  sur- 
face, the  cartilage  is  thereby  given  a  velvety  aspect.  Absorption, 
necrosis,  and  exfoliation  of  the  proliferated  cartilage  appear  later.  From 
the  margin  of  the  cartilage  the  process  extends  to  the  synovial  mem- 
brane— if  this  structure  has  not  been  attacked  earlier — the  connective 
tissue  of  which  becomes  cellular  and  elaViorates  a  chondroid  or  osteoid 
matrix,  in  which  calcific  dej)Osits  form.  The  villi  of  the  synovial  mem- 
brane become  exul)erant,  and  not  uncommonly  loaded  with  fat.  con- 
stituting the  so-called  aborescent  lipoma.  As  a  result  of  myelogenous 
absorption  and  lacunar  atro])hy.  the  density  of  the  articular  end  of  the 
bone  is  lessened,  and,  later,  gelatinoid  or  mucoid  areas  develop  in  its 
interior.  Excavations  occur  on  the  articular  surface  that,  with  lateral 
extensions  from  the  ])eriphery  of  the  articular  cartilages,  entirely  destroy 
the  architecture  of  the  joint.  Osteophytic  growth  from  the  bottom  of 
the  acetaltulum.  with  lateral  extensions  from  the  head  of  the  femur, 
entirely  change  the  character  of  the  joint,  the  acetabulum  becoming 
the  ball  and  the  femur  forming  the  socket.     Such  alteration  in  the  joint 

'  SchuUer,  "Berl.  klin.  Woch  ,"  1900,  Nos.  5,  6,  7.  Curcio,  "Gaz/.  degii  Os- 
pedali  e  delle  Clin.,"  Oct.  30,  1904.  Ruhrah.  "Amer.  four,  of  Med.  Sci,"  Nov., 
1903.  Ed.sall  and  Lavenson.  "Amer.  Jour,  of  Mod.  Sci,"  Dec,  1903.  p.  991. 
McCrac,  "Jour.  Amer.  Med.  Assoc.,"  Oct.  S.  1004,  p.  1027.  Bannatyne,  "Rheu- 
matoid Arthriti.s:  Its  Path<)loj;n>-,  Morbid  Anatomy,  and  Treatment,"  3c  ed..  1904. 
London.  Goldthwait,  "Boston  .Med.  and  Surg.  Jour.."  Nov.  17,  1004.  Richard- 
son, "Boston  Med.  and  Surg.  Jour.,"  March  9.  1905,  p.  263:  see  also  a  number  of 
papers  on  Chronic  Joint  Disease  in  same  journal,  Nov.  17,  1904.  McCarthy,  '  N.  Y. 
Med.  Jour,"  April  S,  1905,  p.  681. 


830  SPECIAL    PATHOLOGY. 

is  not  at  all  characteristic  or  constant,  but  is  mentioned  as  illustrating 
the  remarkable  deformity  with  which  the  process  may  be  associated. 
Detachment  of  portions  of  osteophytic  growth  and  loose  cartilages  with 
separation  of  the  enlarged  iimbnse  give  rise  to  loose  bodies  in  the  joint. 
The  extensive  production  of  osteophytes  and  fibrous  tissue  usually  gives 
rise  to  fixation  or  even  to  ankylosis,  while  the  osseous  resorption  favors 
the  occurrence  of  luxation  or  weakens  the  bone  in  the  neighborhood  of  the 
ioint,  permitting  fracture.  Atrophy  of  muscles  and  wasting  of  adjacent 
structures  make  more  evident  the  articular  deformity. 

Neuropathic  Diseases  of  Joints/ — Spinal  and  neurogenous  arthro- 
pathies are  forms  of  joint-change  commonly  associated  with  locomotor 
ataxia,  with  syringomy,eha,  and  less  frequently  with  compression, 
concussion,  and  other  lesions  of  the  spinal  cord,  including  degenerative 
change  in  the  anterior  horns.  The  disease  is  monarticular  in  about 
eightv  per  cent,  of  the  cases,  and  usually  involves  the  larger  joints, — 
namelv,  the  knee,  hip,  shoulder,  or  elbow, — although  it  is  occasionally 
seen  in  the  smaller  articulations  of  the  hand  and  foot,  and  very  excep- 
tionally in  the  spine.  In  some  cases  osteophytic  growths  occur,  usually 
beginning  in  the  cartilage  and  cellular  elements  of  the  capsule  and  peri- 
articular tissues.  This  constitutes  the  so-called  hypertrophic  form. 
In  the  atrophic  form  degeneration  and  absorption  of  the  articular  surface 
and  part  of  the  adjacent  bone  occur,  with  relaxation  of  the  hgaments, 
permitting  or  favoring  luxation.  The  head  of  the  bone — as,  for  example, 
the  femur — mav  be  completely  absorbed.  Serous  efTusion  into  the  joint 
is  not  infrequently  present;  except  in  the  earlier  stages,  it  is  rarely 
marked.  The  disease  was  studied  by  Charcot,  and  is  frequently  spoken 
of  as  Charcot's  disease  of  the  joints.  The  investigations  of  Wilde  indicate 
that  the  joint  lesion  starts  from  an  injury ;  changes  in  the  sensory  nerves 
render  the  patient  less  susceptible  to  pain,  the  absence  of  which  causes 
neglect  and  perpetuates  the  alterations  in  the  articular  structures  and 
contiguous  bones. 

Tuberculosis  of  joints,  also  called  articular  tuberculosis,  tumor  albus, 
white  swelling,  scrofulous  or  strumous  joint  disease,  fungous  disease  of 
the  joint,  caseous  arthritis,  tuberculous  abscess  of  the  joint,  cold  abscess 
of  the  joint,  and  by  other  names  indicating  either  the  etiology  or  ana- 
tomic changes,  results  from  infection  of  one  or  more  of  the  articular 
structures  by  the  tubercle  bacillus.  The  condition  is  most  frequent  in 
children — over  eighty  per  cent,  of  the  cases  occurring  before  the  fifteenth 
year.  The  disease  commonly  attacks  the  hip,  knee,  or  ankle,  although 
the  shoulder,  wrist,  and  elbow  occasionally  suffer;  a  process  practically 
identical,  affecting  the  vertebrae,  is  called  Potfs  disease  of  the  spine. 
The  disease  is  nearly  always  monarticular;  to  this,  however,  there  are 
occasional  exceptions.  A  history  of  trauma  is  frequently  present;  the 
injury  mav  induce  an  inflammation  that  later  becomes  infected  by  the 
tubercle  bacillus;  it  is  also  probable,  however,  that  trauma'  acts  by 
irritating  or  breaking  open  a  latent  or  quiescent  area  of  tuberculosis  in 
the  adjacent  bone.  It  is  usually  held  that  the  tubercle  bacilH  reach  the 
area  involved  through  the  circulation,  coming  from  a  primary'  lesion 

1  Wilde,  "Deut.  Zeit.  f.  Chir.,"  Oct.,  1902,  Bd.  65.  Bressaud,  "Arch.  Gen. 
de  Med.,"  1903,  No.  52.  Kollarits,  "Neuro.  Centralbl.,"  April  i,  1904,  p.  304 
Frank,  ''Centralbl.  f.'d.  Grenzgehiet.  der  Med.  u.  Chir.,"   Bd.   vii.   No.    17,   1904. 

2  Petrov,  "Zentralbl.  f.  Chir.,"  Nov.  26,  1904. 


HONlvS    AND    JOINTS.  831 

elsewhere,  as,  c.  t^.,  a  latent  tuberculosis  of  the  broiuhial  j^'lands,  or  pos- 
sibly mesenteric  lymph-nodes.  As  already  indicated  (j).  817),  the  initial 
lesion  of  the  process  is  usually  in  the  atJjacent  epiphysis,  from  which  it 
extends  to  the  involved  joint,  cortstitutmg  the  so-called  osteopathic 
variety  of  the  disease.  In  other  cases  the  disease  appears  to  arise  in  the 
synovial  membrane;  in  other  words,  it  is  a  primary  involvement  of  the 
joint,  and  is  calleil  arthropathic. 

Morbid  A}iato}ny. — Recent  studies  seem  to  indicate  that  we  are 
justified  in  recognizing  at  least  two  forms  of  articular  tuberculosis;  one 
IS  the  old  familiar  type  attended  by  extensive  caseation  and  osseous 
absorption,  and  properly  called  caseous  tuberculosis.  In  the  second 
variety  cheesy  masses  are  not  produced,  although  hyperplasia  of  the 
synovial  membranes  and  fibrous  ankylosis  frequently  occur;  this  type 
mav  be  called  chronic  fibrous  or  ankylosing  arthritis. 

Chronic  Caseous  Tuberculosis  of  Joints. — Whether  involving  the 
ioint  from  adjacent  bones  or  beginning  as  a  chronic  synovitis,  the 
process  rapidly  becomes  a  panarthritis.  The  disease  is  occasionally 
preceded  bv  a  stage  of  hydrops  arthrosis.  The  abundant  production 
of  granulation  tissue  occurs  not  only  from  the  synovial  membrane, 
but  the  fungoid  mass  may  be  projected  from  the  tuberculous  bone, 
thus  filling  the  joint  with  granulation  tissue  containing,  in  its  earlier 
progress,  "numerous  tubercles  in  various  stages  of  evolution.  In  this 
tuberculous  tissue  caseation  rapidly  ensues,  distending  the  joint  by 
accumulated  caseous  detritus.  The  joint  capsule  is  more  or  less  rapidly 
invaded;  and  further  extension  of  the  process,  along  the  line  of  least 
resistance,  frequently  occurs.  Like  other  forms  of  tuberculosis,  the 
lesion  is  sometimes  arrested,  and  healing-in  may  occur  at  any  stage  of 
its  evolution.  In  the  majority  of  cases,  however,  destruction  of  the 
joint  takes  place.  The  articular  extremity  is  usually  riddled  by  perfor- 
ations from  which  the  granulation  tissue  projects,  or  such  openings 
communicate  with  the  caseous  areas  in  the  adjacent  zone.  Epiphyseal 
separation  is  sometimes  observed.  With  healing-in,  extensive  calcare- 
ous infiltration  takes  place,  terminating  in  permanent  ankylosis. 

The  dangers  of  this  form  of  tuberculous  arthritis  are  twofold.  In  the 
first  place,  the  local  lesion,  as  a  result  of  the  hematogenous  dissemination 
of  the  tubercle  bacillus,  may  give  rise  to  general  miliary  tuberculosis. 
Extensions  along  the  bone  sometimes  lead  to  tuberculous  osteomyelitis, 
caries,  and  necrosis;  and  disastrous  complications  follow  infection  by 
pvogenic  organisms.  The  weak  protective  powers  i)resent  in  the  diseased 
tissues  favor  inoculation  by  pyogenic  bacteria,  and  in  this  way  there  is 
added  to  the  local  tuberculosis  one  or  more  of  the  dangers  incident  to 
acute  suppurative  osteomyelitis. 

Chronic  fibrous  tuberculous  arthritis'  is  more  likely  to  affect  a  number 
of  joints  simultaneouslv  or  m  succession  than  the  typical  caseous  fomv 
In  this  tvpe  of  the  affection  the  lesion  resembles  the  chronic  hyperplastic 
tuberculosis  of  other  tissues  (p.  153),  and  in  some  cases  possesses  the 
clinical  characters  of  arthritis  defomians.  Caseation  is  inconspicuous 
or  absent,  the  articular  and  para-articular  fibrous  tissues  are  thickened, 
serous  exudates  into  the  joint  occur,  and  connective-tissue  metaplasia 

'  Ed.sall  and  Lavenson.  "  Amer.  Tour  of  Med.  Sci.."  Dec.  iqo.i.  Levison. 
"Jour.  Amer.  Med.  Assoc."  Jan.  23.  1904-  Poncet  and  I^enche.  "Rev.  de  Chir.." 
Jan.  10.  1905,  p.  I . 


832  SPECIAL     PATHOLOGY. 

of  the  cartilage,  and  subsequent  cicatrization,  terminate  in  ankylosis. 
The  danger  of  systemic  infection  is  much  less  than  in  the  caseous  form  of 
the  affection;  it  is  probable  that  many  cases  of  fibrous  joint  tuberculosis 
are  mistaken  for  chronic  rheumatism,  arthritis  deformans,  and  other 
affections,  some  of  which  are  clearly  non-tuberculous. 

Syphilis  of  the  joints^  occurs  in  both  the  inherited  and  acquired  forms 
of  the  affection.  It  may  be  manifested  by  a  hydrops  arthrosis,  chronic 
serous  synovitis  with  the  accumulation  of  considerable  fluid  in  the  joints, 
or  a  chronic  fibrous  ankylosing  inffammation  with  connective-tissue 
metaplasia  of  the  articular  cartilages.  Fournier  has  described  a  de- 
forming type  of  syphilitic  arthritis  resembling  arthritis  deformans. 
Gummata  sometimes  develop  in  the  synovial  membrane  (gummatous 
synovitis),  or,  extending  from  the  epiphysis,  may  involve  the  articular 
cartilage;  in  either  of  these  forms  the  resemblance  to  tuberculosis  is 
clinically  sufficiently  marked  to  justify  the  term  pseudo-white-swelling 
sometimes  given  to  the  affection.  Syphilitic  inflammation  of  the  joints 
is  often  a  polyarthritis. 

Ankylosis  is  the  name  given  to  that  condition  in  which  a  joint 
becomes  useless  by  reason  of  fixation.  The  name  literally  indicates 
angular  deformity,  which  may  or  may  not  be  present.  When  the  fixa- 
tion is  dependent  upon  lesions  around  the  joint,  upon  fibrous  changes  in 
the  joint  capsule,  or  upon  muscular  contraction  and  similar  conditions, 
it  is  said  to  be  a  false  or  pseudo-ankylosis .  On  the  other  hand,  when  the 
fixation  arises  as  a  result  of  structural  changes  in  the  articular  surfaces, 
leading  to  osseous  or  calcific  union  between  the  bones  entering  into  the 
joint,  the  condition  is  called  trite  ankylosis.  Such  ankvlosis  commonly 
follows  protracted  inflammatory  processes  affecting,  the  joint,  suppura- 
tive arthritis,  tuberculosis,  and  similar  inflammatory  or  necrotic  processes. 

Morbid  Anatomy. — The  alterations  observed  in  the  joint  depend 
largely  upon  the  cause.  Theoretically,  in  false  ankylosis  the  articular 
surfaces  are  normal.  There  is  usually  considerable  increase  in  the  fibrous 
tissue  of  the  capsule,  which  may  be  also  calcareous.  Further,  the  capsule 
adapts  itself  to  its  long-continued  quiescent  position,  and,  with  the 
removal  of  the  cause,  if  such  be  possible,  considerable  time  is  necessary 
for  the  reestablishment  of  pliability  and  elasticity  in  the  altered  liga- 
ments. In  true  or  osseous  ankylosis  the  formation  of  new  bone  or 
extensive  calcific  deposits  in  granulation  tissue,  gives  rise  to  fixation. 
Fractures  involving  joints  may,  in  the  process  of  uniting,  permanently 
fix  the  articular  surfaces.  Extensive  calcareous  infiltration  of  in- 
flammatory products  and  inefficient  attempt  at  osseous  repair  may 
entirely   destroy  the   articular  structures. 

*  Morestin,  "Arch.  Gen.  de  Med.,"  1901,  vol.  5.  Hippel,  "Munch,  med. 
Woch.,"  Aug.  4,  1903,  p.  1321;  also  Jordon,  same  journal,  p.  1324.  Paton,  "Brit. 
Med.  Jour.,"  Nov.  28,  1903,  p.  1389.  Fletcher,  "Lancet,"  Nov.  19,  1904.  Dunlop, 
"Edinburgh  Med.  Jour.,"  Dec,  1904. 


(•ii.\rTi:R  XVI. 

THE  NERVOUS  SYSTEM.' 

General  Considerations. — Aiintoniy<^iiid Histology. — It  is  not  within  tlu- 
proviiux'  ol  this  ixMik  to  discuss  in  a  detailed  or  minute  manner 
the  anatomv  of  the  nervous  system,  and  those  who  desire  such  knowl- 
edge are  referred  to  anatomies  and  special  text-books  on  the  subject. 

The  nervous  svstem  is  composed  of  (i)  the  brain  and  spinal  cord, 
which  together  constitute  the  central  nervous  system,  and  (2)  the  periph- 
eral nervous  system,  consisting  of  multitudes  of  nerve-tibers  that  are 
projected  in  small  bundles,  known  as  nerves,  from  both  the  brain  and 
cord  to  the  various  parts  of  the  body;  in  addition  to  the  foregoing, 
there  is  what  is  known  as  (3)  the  sympathetic  nervous  system,  which, 
although  probably  developed  independently,  is  to  be  regarded  as  having 
a  direct  relation  with  the  cerebrospinal  system. 

The  brain  and  cord  are  covered  by  three  connective-tissue  investing 
membranes,  collectively  known  as  the  meninges;  these  are  in  intimate 
relation  with  the  structures  that  they  inclose,  and  are  to  a  certain  ex- 
tent influenced  bv  many  of  the  diseases  of  the  brain  and  cord,  which 
structures  are  also  alTe'cted  in  a  number  of  lesions  beginning  in  the 
overlving  membranes. 

The  covering  directly  in  contact  with  the  surfaces  of  the  brain  and 
cord  is  called  the  pia  mater;  next  to  this  is  a  layer  of  extremely  deli- 
cate tissue  directlv  continuous  with  the  foregoing,  and,  therefore,  to  be 
regarded  as  reallv  a  part  of  it,  known  as  the  arachnoid,  the  two  struc- 
tures constituting  the  pia-arachnoid;  and.  finally,  covering  the  inner 
surface  of  the  skull  and  lining  the  bony  wall  of  the  spinal  canal  is  a 
ver\'  dense,  comparatively  thick  membrane,  which  has  received  the 
name  dura  mater.  The  membranes  around  the  cord  are  continuous 
with  those  covering  the  brain,  of  which  they  are  merely  prolongations; 
these  membranes,  though  becoming  much  thinner,  and  in  part  losing 
their  identitv,  arc  further  projected  as  coverings  of  the  nerves  passing 
from  the  brain  and  cord;  the  dura  becomes  the  epineurinm;  the  arach- 
noid, the  perineurium;  and  the  pia.  the  cndoneurium.  Although  it 
should  be  clearly  understood  that  the  several  membranes  constituting 
the  meninges  are  respectively  the  same  in  both  the  brain  and  cord,  it 
is  equally  important  to  know  that  they  differ  frOni  one  another  in  several 
minor  particulars. 

Histology  of  the  Membranes.— The  pia  and  arachnoid  are  composed 
of  delicate  bundles  of  tiV)rous  tissue,  upon  which  lie  many  small,  flattened 
cells;  the  outer  surface  of  the  arachnoid  is  covered  by  a  continuous 
layer  of  large  polvgonal.  but  extremely  thin,  endothelium.  Processes 
from  the  pia  penetrate  the  substance  of  both  the  brain  and  cord; 
these  processes  carr>-  blood-vessels,   and  enter  into  intimate  relation 

'  For  method  of  examination  see  pp.  21  to  25. 
54  833 


834  SPECIAL    PATHOLOGY. 

with  the  pecuUar  supporting  structure  of  the  central  nervous  system, 
known  as  the  neuroglia.  From  the  surface  of  the  arachnoid,  especially 
on  each  side  of  the  superior  longitudinal  fissure,  bulbous  projections 
occur;  these  penetrate  the  dura,  and  are  called  the  Pacchionian  bodies. 
Both  the  pia  and  arachnoid  are  extremely  vascular;  the  blood-vessels 
are  particularly  numerous  in  those  prolongations  of  the  former  that 
enter  the  ventricles  and  are  called  the  velum  interpositum  and  the 
choroid  plexus.  The  velum  interpositum  and  the  choroid  plexus  are 
covered  by  cuboid  epithelial  cells,  which  in  the  new-born  are  ciliated. 

Both  the  inner  and  outer  layers  of  the  dura  are  composed  of  com- 
pact bundles  of  fibrous  and  elastic  tissues— those  in  the  outer  being 
placed  transversely  to  those  on  the  inner  coat.  This  coat  contains  only 
a  few  blood-vessels. 

The  brain  comprises  those  parts  of  the  central  nervous  system  within 
the  cranial  cavity;  they  are  the  cerebrum,  the  cerebellum,  the  pons 
varolii,  and  the  medulla  oblongata — the  last  of  which  passes  into  the 
spinal  canal,  and  becomes  continuous  with  the  spinal  cord.  The  brain  as 
a  whole  is  oval  in  form;  the  upper  surface,  although  very  uneven,  pre- 
sents a  fairly  regular  convexity,  while  the  under  surface  is  somewhat 
flattened  and  is  much  more  irregular  in  appearance.  The  average 
weight  of  the  adult  brain  in  man  is  somewhere  near  1350  gm.  to  1400 
gm.,  and  in  woman,  1235  gm.  to  1275  gm.  While  it  is  true  that  con- 
siderable variation  from  the  foregoing  in  either  direction  is  not  incon- 
sistent with  perfect  health  and  even  with  great  intellectual  activity, 
the  brains  of  idiots  and  of  the  intellectually  feeble  are,  as  a  rule,  con- 
siderably below  the  average  weight.^ 

The  spinal  cord  extends  from  the  upper  border  of  the  atlas  to  the 
bodv  of  the  second  lumbar  vertebra,  where  it  terminates  in  a  slender, 
somewhat  conic  body  called  the  filum  terminale.  The  latter  is  sur- 
rounded by  a  number  of  nerve  bundles  known  as  the  cauda  equina. 
The  cord  is  about  forty-five  centimeters  long  and  weighs  about  thirty 
grams.  As  a  whole,  it  is  irregularly  cyHndric  in  form,  tapering  at  its 
lower  end,  and  forming  what  is  called  the  conus  niedullaris.  Antero- 
posteriorly  it  is  somewhat  flattened;  in  the  lower  cervical  and  upper 
lumbar  regions  it  swells  slightly,  producing  two  areas  of  increased  size, 
known  as  cervical  and  lumbar  enlargements  respectively.  It  is  divided 
in  front  by  a  groove,  called  the  anterior  median  fissure;  and  behind  by 
a  septum,  termed  the  posterior  median  septum  (posterior  median  fissure 
of  some  authors).  Two  quite  distinct  furrows  are  situated  on  the  pos- 
terior aspect  of  the  cord  at  the  points  of  exit  of  the  posterior  nerve-roots, 
which  is  a  little  external  to  the  median  septum;  these  depressions  are 
called  the  posterolateral  grooves.  Anterior  fissures  corresponding  to 
the  point  of  origin  of  the  anterior  nerve-roots  are  described  by  some 
authors;  recent  researches  into  the  location  of  the  different  functional 
tracts  of  the  cord  go  to  show  that  the  anterior  and  motor  columns  are 
physiologically  identical;  and,  further,  as  there  is  no  sui^cient  anatomic 
reason  for  the  belief  in  a  distinct  fissure  along  the  line  of  exit  of  the 
anterior  roots,  its  description  seems  unnecessary. 

1  For  more  specific  statements  as  to  brain  weight  see  Marchand,  "Abh.  d. 
math.  phys.  Classe  d.  Konigl.  Sachsischen.  Ges.  d.  Wissensch.,"  Bd.  xxvii,  1902. 
No.  iv,pp'.  393-482.  Spitzka,  "  Phila.  Med.  Jour.,"  May  2,  1903;  also  "Science," 
Sept.  18,  1903,  p.  371. 


TIM-;     NKKVOUS    SYSTEM.  835 

The  nerves  arisiiiy,'  from  ihc  1  train  and  spinal  c(;nl  consist  of  a  nun;- 
ber  of  separate  huntlles  of  nerve-tibers,  each  of  which  is  incased  in  a 
sheathing  of  fibrous  tissue,  and  all  the  bundles  are  connected  an«l  sur- 
roundcil  l»v  an  outer  layer  of  fibrous  tissue  which  becomes  continuous 
witli   the   iicii,dib<>riiiv(  slnuturcs. 

Histology  of  the  Nervous  System.'  -The  entire  nervous  system,  in 
both  nuin  and  lower  animals,  consists  of  multitudes  of  extremely  delicate 
fibrils  which  unite  to  fomi  a  sinj^^le  element  (the  neuron),  made  u])  of  a 
cell — the  ncrrc  icll  or  iia)iiilio)i  cell — and  numerous  processes,  one  of 
which,  in  certain  varieties  of  the  cell,  becomes  the  axis-cylinder  of  a 
nerve,  and  in  this  form  extends  to  the  point  of  peripheral  distribution; 
notwithstanding  that  these  cells  are  all  fundamentally  identical,  certain 
later  differentiations  occur,  giving  rise  to  morphologic  and  tinctorial 
differences,  justifying  their  division  into  a  number  of  \arieties  The 
nerve  elements  proper  are  united  by  a  tissue  called  the  neuroglia. ■'  The 
neuroglia  consists  of  numerous  small  cells  between  which  are  multitudes 
of  hbrils  that  in  the  adult  probably  have  no  connection  with  the  cells; 
the  relation  between  the  hbrils  and  cells  is.  however,  so  intimate  that 
the  former  have  been  generally  described  as  processes  of  the  latter,  and 
together  they  are  spoken  of  as  moss  or  spider  cells,  depending  upon  their 
individual    peculiarities. 

The  structures  composing  the  neurons  and  also  the  neuroglia  fibers 
and  cells  are  believed  to  V>e  derived  from  the  epiblastic  tissues  of  the 
bodv,  and  should  be  looked  upon  as  but  modified  epithelial  cells.  Al- 
though not  of  connective-tissue  origin,  the  neuroglia  in  pathologic  pro- 
cesses affecting  the  central  nervous  system  comports  itself  in  a  manner 
resembling  the  changes  occurring  in  fibrous  tissue  which  constitutes 
the  interstitial  structure  of  other  organs;  when  inflammation  or  de- 
generation destroys  the  functionally  higher  tissue — ganglion  cells  and 
fibers — the  neuroglia  increases  in  a  way  corresponding  to  the  increased 
connective  tissue,  for  example,  in  the  heart  after  destructive  meta- 
morphoses of  the  cardiac  muscle.  The  processes  affecting  the  central 
nervous  system,  and  included  under  the  general  term  sclerosis,  are 
constantlv  associated  with  the  disappearance  of  the  elements  that  enter 
into  the  formation  of  neurons  an<l  more  or  less  hyperplasia  of  the  sus- 
tentacular  tissue — the  neuroglia. 

Ganglion  cells  are  found  principally  in  the  gray  matter  of  the  central 
nervous  svstem,  but  are  also  present  in  the  sympathetic  ganglia,  in  the 
ganglia  occurring  in  the  course  of  cerebrospinal  nerves,  and  in  the  organs 
of  special  sense.  The  cells  vary  in  size  from  4  w  to  135  ;/.  There  are  a 
few  oval  or  spindle-sha})ed  ganglion  cells,  but  the  vast  majority  possess 
irregular  forms  due  to  the  abundant  processes  that  emanate  from  them. 
Cells  possessing  a  single  process  are  called  unipolar  (occur  in  man  in  the 
olfactory'  mucous  membrane);  if  two  processes  are  present,  they  are 
termed  bipolar;  and  if  more  than  two,  niulti polar.  The  processes  pro- 
jecting from  one  end  of  a  ganglion  cell,  after  proceeding  a  short  distance. 

'  For  recent  studies  dealing  with  the  tiner  histolnjn,-  of  the  central  nervous 
svstem.  consult,  Dejerine.  "Revue  Xeuroloj;.,"  Ntarch  15.  1004,  p.  205.  Bethe, 
■  Deut.  med.  Woch.,"  Aug.  11,  1904.  Azoulay.  "La  Presse  M6d.,*  July  23,  1904. 
and  .Vup.  24.  1Q04. 

*  For  recent  views  as  to  the  origin  and  nature  of  neuroglia  see  Hardesty.  "  Amer. 
lour,  of  Anatomv."  Julv  i,  1904.  vol.  x.  No.  3. 


836  SPECIAL    PATHOLOGY. 

break  up  into  numerous  smaller  branches,  known  as  dendrites,  which 
again  subdivide,  and  their  smallest  extensions  exhibit  multitudes  of 
minute  projections  termed  gcmmuke;  the  former  have  not  inaptly  been 
compared  to  the  limbs  of  a  tree,  and  the  latter  to  the  leaves.  From 
some  other  part,  usually  the  other  end  of  the  nerve-cell,  another  process 
passes  out,  which  may  continue  as  an  axis-cylinder  of  a  nerve-fiber,  or, 
after  going  a  short  distance,  may  turn  on  itself  and  divide  into  a  number 
of  processes  resembling  the  dendrites  arising  from  other  parts  of  the  cell. 
Cells  the  processes  of  which  become  axis-cylinders  are  called  cells  of  the 
first  type,  and  those  whose  processes  fail  to  form  axis-cylinders  are  termed 
cells  of  the  second  type.  All  the  peculiarities  of  the  ganglion  cells  so  far 
mentioned  can  be  brought  out  with  distinctness  only  by  the  method  of 
preparation  devised  by  Golgi.  This  method,  as  slightly  modified  by 
Berkley,  is  as  follows: 

To  get  good  results  the  tissue  must  be  perfectly  fresh.  It  should 
be  hardened  in  Miiller's  solution  (see  p.  31)  until  it  becomes  sufficiently 
hard  to  admit  of  fairly  thin  sections  being  cut;  this  requires,  at  ordinary 
temperatures,  about  three  weeks.  The  fluid  should  be  abundant  and 
should  be  changed  daily  for  the  first  few  days.  The  tissue  is  then  cut 
into  pieces  not  exceeding  three  millimeters  in  thickness,  and  placed  in 
the  following  solution,  which  should  be  freshly  prepared: 

Bichromateof  potassium,  3  per  cent,  solution  in  water,  100  parts. 
Osmic  acid  (OsO^) ,  i  per  cent,  solution  in  water, ....      30 

After  three  days  remove  the  specimens  and  imbibe  the  excess  of  the 
foregoing  solution  with  filter-paper;  wash  for  a  few  minutes  in  a  weak 
solution  of  silver  nitrate  in  water.  The  tissue  is  now  placed  in  the 
following  solution: 

Phosphomolybdic  acid,  10  per  cent,  solution  in  water,    2  drops. 
Silver  nitrate,  i  per  cent,  solution  in  water, 60  c.c. 

This  mixture  should  be  prepared  just  before  being  used.  In  the 
mixture  the  tissue  should  remain  undisturbed  for  two  or  three  days, 
or,  if  desirable,  it  may  be  kept  indefinitely  by  adding  a  few  drops  of  the 
silver  nitrate  solution  at  the  expiration  of  the  time  mentioned.  During 
the  process  of  preparation  it  is  perhaps  better  to  keep  the  jars  containing 
the  mixture  in  the  dark.  Impregnation  goes  on  best  at  about  25°  C. 
After  the  foregoing  the  tissues  are  placed  in  absolute  alcohol  for  an  hour 
and  are  then  quickly  embedded  in  celloidin.  (See  p.  42.)  Sections  are 
examined  without  staining.  By  this  method  the  nerve-cell  and  its 
processes  are  impregnated  with  the  silver  salt  and,  though  unstained,  are 
rendered  a  uniform  brownish-black  color.  The  impregnation  is  at  best 
very  capricious — some  of  the  cells  darkening  intensely  and  others  in  the 
immediate  vicinity,  not  at  all.  The  neuroglia  cells  and  the  fibrils 
around  them  are  also  tinged.  Golgi's  method  is  useful  only  as  a  stain 
for  the  outlines  of  the  cells  and  their  processes,  and  it  therefore  becomes 
necessary  to  employ  other  means  if  it  is  desired  to  study  the  mternal 
structure  of  these  bodies. 

The  ganglion  cells  have  no  distinct  cell-membrane.  They  possess  a 
reticular  protoplasm  that  stains  with  acid  dyes;  the  greater  number  of 
the  ganglion  cells  contain,  within  the  reticulum,  a  substance  that  takes 


THE    NERVOUS    SYSTEM.  S;?7 


I ut>ir 


,  ..  .-  lives  intcnsrlv.  These  basophilic  masses  arc  called  the  tigroid 
substance  or  bodies  of  Nissl.  In  the  great  majority  of  nerve-cells  tlic 
nuclei  do  not  take  basic  stains,  althou.gh  they  contain  a  delicate  reticu- 
lum and  a  nuclear  wall,  both  of  which  are  acidophilic.  As  a  result  of 
this  peculiarity,  when  the  tissues  are  stained  in  the  usual  way,  the  nu- 
cleus api)ears  as  an  almost  unstained  or  but  lit^htly  tinged,  round  space. 
Within  the  nucleus  is  a  nucleolus  that  stains  intensely  with  basic  dyes. 

Xissl  classifies  nerve-cells  into  {a)  karyochromes,  or  cells  the  nuclei 
of  which  take  basic  stains;  and  (b)  somatochromes,  or  cells  only  the 
protoplasm  of  which  takes  the  basic  dye.  Tlie  lonner  are  comparatively 
rare,  but  are  found  in  the  olfactory  lobe,  the  cerebellum,  and  the  retina. 
The  latter  have  been  subdivided  into  several  diflferent  varieties,  depend- 
ing upon  the  arrangement  of  Nissl's  basophilic  or,  as  they  are  also  called, 
chromophilic  or  tigroid  bodies:  (i)  Arkyochromcs,  or  cells  in  which 
the  chromophilic  substance  is  arranged  in  rows;  (2)  stichochromcs,  or 
cells  in  which  the  chromophilic  substance  is  arranged  more  or  less 
regularlv  throughout  the  cell;  (3)  gryochromcs,  or  cells  in  which  the 
chromophilic  substance  occurs  in  tine  granules;  (4)  arkystichochromes,  or 
cells  in  which  some  combination  of  the  preceding  is  present.  The 
chromophilic  substance  is,  as  a  rule,  tolerably  uniformly  distributed 
throughout  the  cell;  it  is,  however,  worthy  of  note  that  just  beneath 
the  point  where  the  axis-cylinder  process  emerges  from  the  cell  this 
substance  is  largelv  absent.'  In  conclusion,  it  should  be  noted  that  in 
many  ganglion  cells  there  are  small  collections  of  yellowish-brown 
pigrnent,  situated  in  the  protoplasm  just  outside  of  the  nuclear  wall; 
the  quantity  of  this  pigment  increases  with  age  and  under  pathologic 
conditions. 

Method  of  Demonstration. — The  method  first  employed  for  the  pur- 
pose of  demonstrating  the  previously  mentioned  peculiarities  of  ganglion 
cells  was  that  of  Xissl.  Blocks  of  tissue  not  over  one  centimeter  in 
thickness  are  hardened  in  ninety-six  per  cent,  alcohol.  The  hardened 
tissue  is  removed  from  the  alcohol'and  gently  blotted  with  bibulous  paper; 
dip  the  piece  of  tissue  in  thick  celloidin  (p.  42)  and  attach  it  to  a  block 
prepared  as  directed  (p.  42).  Do  not  embed.  Harden  the  celloidin  in 
ninetv  per  cent,  alcohol  and  section  with  knife  wet  in  alcohol  of  the 
same  strength.  (Directions  for  cutting  celloidin  sections  see  p.  43.) 
Preserve  sections  in  ninety  per  cent,  alcohol.  The  stain  used  is  a  soapy 
solution  of  methylene-blu'e  (methylene-blue.  B. patent),  and  had  best  be 
purchased  as  prepared  bv  Grubler,  who  has  placed  it  on  the  market  under 
the  name  'Soapv  Solution  of  Methylene-blue  "  (Nissl).  The  sections  are 
placed  in  this  solution  and  heated  until  bubbles  form;  they  are  then 
washed  in  a  mixture  composed  of  anilin  oil  (10  parts)  and  ninety-six 
per  cent,  alcohol  (go  parts)  until  ditTercntiation  is  completed.  The 
sections  are  now  placed  on  the  slide,  blotted  with  filter-paper,  and 
cleared  in  oil  of  cajuput.  Wash  off  the  oil  with  l)enzin  and  mount  in 
a  solution  of  colophony  in  benzin;  the  cement  is  applied  and  is  gently 
warmed  in  order  to  vaporize  the  benzin;  if  the  benzin  inflames,  blow  out 
the  flame  and  continue  the  warming;  finally,  when  the  benzin  has  been 
expelled,  applv  a  cover-glass. 

In  the  hands  of  the  author  the  following  method  has  given  better 
and  more  uniform  results:  Fix  the  tissues,  which  should  be  as  fresh  as 
possil)lc.  in  mercury  bichlorid  .solution  (p.  34).  embed  in  paraffin  (p.  35), 


838  SPECIAL     PATHOLOGY. 

section,  and  cement  to  the  slide  in  the  usual  way;  remove  the  paraffin, 
wash  in  alcohol  followed  by  water,  and  stain  sections  for  from  five  to 
thirtv  minutes — twelve  to  twenty-four  hours  will  do  no  harm — in  the 
following  solution: 

Toluidin-blue i -5   gm- 

Carbolic  acid,  5  ])er  cent,  solution  in  water 100. o  c.c. 

This  solution  keeps  indefinitely.  After  staining,  thoroughly  wash  the 
section  in  water  and  differentiate  in  styrone  (p.  49),  Unna's  glycerin-ether 
mixture  (p.  49),  water  containing  one  per  cent,  acetic  acid,  or  alcohol; 
again  wash  with  water,  quickly  dehydrate  in  ordinary  alcohol,  and  clear 
in  cedar  oil.  The  chromophilic  substance  is  stained  a  dark  blue,  the 
intensity  of  which  depends  on  the  extent  to  which  the  differentiation 
has  been  carried.     (See  Remarks  on  Staining,  pp.  48  to  50.) 

Thionin  is  chemically  closely  related  to  toluidin  blue  and  may  be 
used  in  the  same  manner;  the  following,  however,  is  recommended:  Fix 
blocks  of  tissue,  not  over  i  cm.  in  thickness,  in  ten  per  cent,  aqueous 
solution  of  formahn  for  twenty-four  hours,  dehydrate  as  directed  on 
page  35,  infiltrate  in  celloidin  (p.  42),  and  section  as  usual.  The  sec- 
tions are  transferred  to  water,  from  which  they  are  placed  in  a  one 
per  cent,  aqueous  solution  of  thionin  for  from  one  to  five  minutes;  wash 
in  water  until  the  excess  of  dye  is  removed  and  differentiate  in  a  mix- 
ture composed  of  anilin  oil  10  c.c.  and  absolute  alcohol  90  c.c.  As 
soon  as  the  section  becomes  a  pale  blue,  wash  rapidly  in  ninety-five 
per  cent,  alcohol,  clear  in  xylol,  and  mount  in  balsam.  The  color  re- 
actions in  the  stainable  substances  are  practically  the  same  as  those 
given  above  for  toluidin  blue. 

Neurofibrils.^ — The  studies  of  Bethe,  Apathy,  Simarro,  Cajal,  and 
others  have  shown  that  important  components  of  the  neurone  are  ex- 
tremely delicate  fibrils,  some  of  which  are  within  the  ganglion  cells 
and  are  projected  into  the  axis-cylinders;  other  fibrils  are  pericellular. 
Of  a  number  of  methods  that  have  been  recommended  for  the  demon- 
stration of  these  bodies,  the  following  (Cajal)  has  been  found  acceptable  ; 
Harden  specimens  about  3  mm.  in  thickness  in  100  c.c.  of  alcohol  con- 
taining I  c.c.  of  ammonia  for  from  twxnty-four  hours  to  three  days: 
wash  in  distilled  water,  transfer  to  1.5  per  cent,  aqueous  solution  of 
nitrate  of  silver  for  from  three  to  five  days  at  30°  C.  to  35°  C.  Com- 
plete the  reduction  of  the  silver  by  allowing  the  specimens  to  remain 
for  twenty-four  hours  in  a  mixture  composed  of  formalin  5  c.c,  pyro- 
gallic  acid  2  gm.,  distilled  water  100  c.c.  Infiltrate  in  paraffin  or  cel- 
loidin and  section;  dehydrate  the  sections,  clear  with  xylol,  and  mount 
in  balsam.     The  impregnated  fibrils  are  black  or  brownish-black. 

Myelin  stains:  In  the  great  majority  of  instances  the  processes  of 
the  nerve-cells  that  become  axis-cylinders  of  nerves,  in  a  short  distance 
after  passing  from  the  cells,  are  enveloped  by  a  stratum  of  a  peculiar 

^  Cajal,  "C.  R.  See.  de  Biol.,''  1903,  tome  v,  p.  1565;  and  Feb.  27,  1Q04,  p. 
368;  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.. "  1904,  No.  3,  p.  122;  also  "Traba- 
jos  del  laboratorio  de  inve-stigaciones  de  la  Universidad  de  Madrid,"  Dec.  28,  1903, 
pp.  129-221.  Chilesotti.  "Zeit.  f.  Wissensch.  Mikros.  u.  f.  Mikroscopische  Tech- 
nik,"  Dec.  2,  1902,  p.  161.  Marinesco,  "Revue  Neurolog.,"  May  15,  1904,  p.  405. 
Biart,  "Med.  Record,"  August  6,  1904,  p.  217.  Bielchowsky,  "Jour.  f.  Psychol, 
u.  Netirol.,"  1904,  Bd.  3,  fasc.  4,  p.  30. 


THE     NEK  vol's    SYSTEM.  A  l,i) 

substance,  nearly  related  to  fat.  an«l  known  as  myelin  or  tlie  white  .siib- 
sUoHc  of  Sclnvinni.  After  this  substance  surrounds  the  axis-cylintler 
it  is  difficult  so  to  stain  the  latter  that  it  can  be  differentiated  from  the 
tissues  with  which  it  happens  to  be  in  contact.  As  the  myelin  sheath 
accompanies  it  almost  to  its  termination,  attention  has  been  directed 
to  staining  this  covering  rather  than  the  axis-cyliniler  itself;  coloration 
of  the  mvelin  sheath  is  accomplished  in  a  most  beautiful  manner  l)y  the 
methods  of  Wcigcrt  or  some  motlitication  of  his  jjrocesses. 

Blocks  of  tissue  i  cm.  to  2  cm.  in  ma.ximum  diameter  are  hardened 
m  Muller's  fluitl  until  they  acquire  a  dark  brown  color;  this  generally 
takes  from  six  to  eight  weeks,  and  may  be  slightly  hastened  by  keeping 
the  tissues  warm  (30°  C.  to  35°  C.)  and  frecjuently  changing  the  solution. 
Rinse  off  the  excess  of  Muller's  fluid,  dehydrate  (p.  35),  and  infiltrate 
with  celloidin  (p.  44).  The  sections  should  be  relatively  thick,  20  » 
to  30  «;  thev  are  rinsed  in  water  and  transferred  to  stain  possessing 
the  following  composition:  Dissolve  10  gm.  of  hematoxylin  (cr\'stals 
or  powder)  in  go  c.c.  of  absolute  alcohol;  prepare  the  stain  to  be  used 
bv  adding  10  c.c.  of  the  alcoholic  solution  of  hematoxylin  to  90  c.c.  of 
water  containing  i  c.c.  of  a  saturated  afjueous  solution  of  carbonate 
of  lithium.  The  alcoholic  solution  of  hematoxylin  should  have  been 
ripened  by  exposure  to  the  light  for  at  least  two  weeks;  the  saturated 
aqueous  solution  of  carbonate  of  lithium  may  also  be  kept  on  hand, 
but  the  final  stain  must  be  freshly  prepared  from  the  stock  solutions. 
Sections  are  left  in  the  stain  for  twenty-four  hours,  after  which  they 
are  removed  and  thoroughly  washed  in  water.  The  differentiation 
is  accomplished  in  a  solution  composed  of  borax  2  gm..  ferricyanid  of 
potassium  2.5  gm.,  water  100  c.c.  which,  for  the  beginner,  had  best  be 
diluted  with  an  equal  volume  of  water.  The  sections  are  lightly  agi- 
tated in  the  differentiating  solution  until  the  white  and  gray  substances 
are  clearly  differentiated,  the  length  of  time  necessary  varying  accord- 
ing to  the  strength  of  the  differentiating  solution  used.  The  sections 
are  then  washed  through  several  changes  of  water,  dehydrated  in  ninety- 
five  per  cent,  alcohol,  cleared  in  a  mixture  called  carl)olxylol, — whi(^h 
consists  of  carbolic  acid  cr\'stals  r  part,  xylol  3  parts, — and,  finally, 
they  are  mounted  in  balsam.  When  stained  by  the  method  just  given, 
all  parts  of  the  section  not  colored  by  the  hematoxylin  are  yellowish, 
and  if  it  is  especially  desired  to  photograph  the  specimen.  Pal's  method 
of  decolorization  may  be  used.  The  tissue  is  prepared  by  the  method 
given  al>ove.  and  the  sections  cut  and  stained  with  the  hematoxylin-car- 
bonate  of  lithium-water  mixture  as  already  directed.  They  are  then 
washed  in  water  and  transferred  to  a  solution  composed  of  potassium 
permanganate  0.25  gm.  and  water  100  c.c.  in  which  the  gray  substance 
turns  a  brownish-yellow.  The  time  re(|uired  for  this  stage  is  usually 
brief,  varying  between  thirty  seconds  and  five  minutes.  The  .sections 
are  at  once  transferred  to  a  solution  consisting  of  oxalic  acid  i  gm.. 
sulphid  of  potassium  i  gm..  water  200  c.c  In  a  few  seconds  the  gray 
matter  becomes  colorless  and  the  specimen  should  lie  (juickly  placed 
in  water,  several  changes  of  which  are  necessary  to  remove  the  last 
traces  of  the  differentiating  solution.  Finally  each  section  is  dehy- 
drated in  ninety-five  per  cent,  alcohol,  cleared  in  carbolxylol  and  mounted 
in  balsam.  By  the  foregoing  myelin  sheath  stains  this  sul)Stance, 
when  normal,  is  tinged  a  deep  purple  or  almost  black,  and  the  presence 


840  SPECIAL    PATHOLOGY. 

of  degenerative  or  necrotic  processes  is  indicated  by  the  absence  of, 
or  abnormality  in  the  myeHn  reaction. 

In  addition  to  the  purely  nervous  elements  of  the  central  nervous 
system,  there  is  a  supporting  structure,  as  has  been  before  remarked, 
known  as  the  neuroglia.  This  consists  of  numerous  small  cells,  termed 
glia  cells,  and  a  tangled  mass  of  fibrils  that  closely  surround  the  cells 
and  the  various  nerve  elements;  it  is  not  probable  that  these  fibrils 
are  really  connected  with  the  glia  cells.  The  latter  are  seen  after  pre- 
paring tissues  in  the  ordinary  way,  but  the  fibrils  are  brought  out  only 
by  special  methods, ^  of  which  that  devised  by  Mallory  is  recommended. 
The  first  step  in  this  process  is  the  preparation  of  phosphotungstic 
hematoxylin,  which  is  made  by  dissolving  o.i  gm.  of  hematoxylin  in 
80  c.c.  of  water,  using  heat  if  necessary,  and,  when  cool,  adding  20  c.c. 
of  a  10  per  cent,  aqueous  solution  of  phosphotungstic  acid  (Merck). 
It  is  usually  necessary  to  ripen  this  mixture  artificially  by  the  addition 
of  0.2  c.c.  of  hydrogen  peroxid.  The  tissues  are  fixed  in  10  per  cent, 
aqueous  solution  of  formalin  for  four  days  and  are  then  placed,  for  an 
equal  length  of  time,  in  a  saturated  aqueous  solution  of  picric  acid. 
From  the  latter  mixture  they  are  transferred  to  a  five  per  cent,  aqueous 
solution  of  bichromate  of  ammonium,  in  which  they  should  remain 
from  three  to  four  weeks  at  room-temperature  or  four  to  six  days  at 
37°  C;  dehydrate  as  directed  on  page  35  and  imbed  in  celloidin  (p.  42). 
The  sections  are  transferred  to  a  solution  consisting  of  potassium  per- 
manganate 0.5  gm.,  water  100  c.c,  for  twenty  to  thirty  minutes;  they 
are  then  washed  in  water  and  placed  in  a  five  per  cent,  aqueous  solu- 
tion of  oxalic  acid  for  from  one  to  two  hours.  Wash  thoroughly  in 
water  and  stain  in  the  phosphotungstic  acid  hematoxylin  for  from  one 
to  two  days,  wash  lightly  in  water  and  transfer  to  a  freshly  prepared 
twenty  per  cent,  alcoholic  solution  of  ferric  chlorid  for  from  ten  to 
twenty  minutes.  The  latter  solution  must  be  removed  by  thorough 
washing  in  several  changes  of  water,  dehydrate  in  ninety-five  per  cent, 
alcohol,  clear  in  oleum  origani  cretici  and  mount  in  xylol  balsam.  The 
neuroglia  fibers  are  stained  a  transparent  blue  and  the  nuclei  and  any 
fibrin  present  are  similarly  tinged. 

The  white  substance  of  the  central  nervous  system  consists  of  axis- 
cylinders  surrounded  by  myelin,  and  imbedded  in  neuroglia.  The  gray 
matter  is  composed  of  ganglion  cells  and  their  processes,  bound  together 
by  neuroglia.  The  ganglion  cells  of  the  gray  substance  show  certain 
pecuHarities  in  different  situations;  as  examples  of  this  may  be  cited 
the  arrangements  and  especial  characteristics  of  the  cells  of  the  gray 
matter  of  the  cerebrum,  of  the  cerebellum,  and  of  the  spinal  cord.  In 
the  cerebral  cortex  the  gray  matter  begins  just  beneath  the  pia.  The 
outer  layer  of  this  structure  contains  only  protoplasmic  processes, 
derived  from  the  underlying  pyramidal  cells,  and  neurogha,  and  is 
called  the  molectdar  layer;  immediately  beneath  this  is  the  layer  of 
small  pyramidal  ganglion  cells.  Underlying  and  adjacent  to  the  last- 
named  stratum  is  another  layer,  also  resembling  the  first,  but  the  ganglion 
cells  are  longer  than  in  the  layer  last  referred  to,  and  are  called  the  large 
pyramidal  cells.  Still  deeper,  and  forming  the  deepest  stratum  of  gray 
matter,  is  a  fourth  layer,  in  which  the  nerve  cells  are  irregular  in  form, 

■^  V  Mallorv  and  Wright,  "Pathological  Technic,"  1904,  pp.  348  to  353.     See  also 
Bartel,   "Zeit.  f.  jWissen.   Mikro.,"  Aug.   i,   1904,  p.   18. 


THE    NERVOUS    SYSTEM.  84I 

and  are  hence  termed  polyntorphoK^.  From  most  ot  these  cells  axis- 
cylinders  of  nerves  arise. 

The  outer  part  of  the  gray  matter  of  the  cerebellar  cortex  is  also 
termed  the  molecular  layer.  In  it  are  two  kinds  of  nerve-cells — the  small, 
occupying  the  outer  part  of  the  layer,  and  the  large  or  basket  cells,  lying 
more  deeply.  Beneath  the  molecular  layer  is  a  very  thin  stratum 
containing  the  cells  oj  Pnrkinje.  These  cells  are  very  large,  and  send  off 
abundant  protoplasmic  processes;  they  are  unique  in  that  they  are  the 
only  ganglion  cells  in  the  cerebellum  from  which  arise  axis-cylinders  that 
become  nerves.  Beneath  the  molecular  layer  is  a  granule  layer  contain- 
ing numerous  cells,  some  of  which  are  slightly  larger  than  others.  The 
nuclei  of  these  cells  stain  intensely,  and  hence  belong  to  the  group  of  cells 
called  karyochromes. 

The  anterior  cornua  in  the  spinal  cord  also  contain  numerous  large 
multipolar  ganglion  cells.  From  the  seventh  cervical  to  the  third 
lumbar  segments  a  group  of  nerve-cells  hes  in  the  inner  part  of  the  neck 
of  the  posterior  horn  and  constitutes  the  column  oj  Clarke.  The  neuroglia 
cells  are  very  numerous  immediately  around  the  central  canal  of  the  cord, 
which  area  is  often  called  the  substantia  gelati)iosa  centralis. 

The  arteries  of  the  central  nervous  system  are  abundantly  supplied 
with  elastic  tissue,  the  contractility  of  which,  under  normal  conditions, 
is  not  lost  with  age;  for  this  reason  it  is  thought  that  ordinarily  the  mind 
does  not  correspondingly  fail  along  with  the  strength  and  other  bodily 
functions  in  old  age. 

The  nerves  passing  from  the  brain  and  cord  consist  of  numerous 
bundles  of  nerve-fibers  inclosed  in  a  common  sheath  of  fibrous  tissue, 
called  the  epineurium.  The  individual  bundles  are  surrounded  by  a 
sheath,  continuous  with  the  foregoing,  termed  the  perineurium;  the 
last-named  structure  sends  processes  between  the  nerve-fibers,  which 
support  the  blood-vessels,  and  constitute  the  endoneurium.  Around 
each  individual  nerve-fiber  there  is  a  delicate  connective-tissue  mem- 
brane, known  as  the  primitive  sheath,  within  which  is  the  myelin  cover- 
ing that  surrounds  the  axis-cyhnder.  It  should  be  remembered,  how- 
ever, that  the  myelin  sheath  is  not  present  in  the  nerves  of  the 
svmpathetic  system,  and  is  occasionally  absent  in  the  cerebrospinal 
nerves.  When  the  myelin  sheath  occurs,  it  is  interrupted  at  regular 
intervals;  such  interruptions  are  known  as  the  constrictions  or  nodes  of 
Ranvier:  at  these  points  the  axis-cylinder  and  the  primitive  sheath 
come  directlv  in  contact.  When  nerves  branch,  they  always  do  so  at 
these  constrictions.  Just  before  the  nerve  ends  the  myelin  sheath 
terminates,  and  the  axis-cyhnder  is  continued  onward  inclosed  only  in 
its  primitive  sheath. 

MALFUR.MATlU.Nb  OF  THE  BRAI.X   A.ND  MM.XAL  i»'i<l^ 

The  brain  and  spinal  cord  take  their  origin  from  the  formation 
and  subsequent  invagination  and  closing-over  of  a  depression  in  the 
superior  germinal  layer,  known  as  the  medullary  groove.  After  closing, 
this  groove  forms  a  cylindric  canal,  known  as  the  medullary  tube  {neural 
tube),  the  walls  of  which  are  formed  by  the  invaginated  epiblastie  tissues 
from  the  superior  germinal  layer  ju.st  mentioned.  This  tube  occupies 
the  position  in  the  embryo  corresponding  to  that  of  the  future  spinal 


842 


SPECIAL    PATHOLOGY. 


cord  and  brain.  The  cord  is  formed  from  the  posterior  part  of  the  tube, 
while  the  brain  is  developed  from  three  saccular  dilatations,  known  as 
vesicles,  which  form  toward  its  anterior  end;  the  first  and  third  of  these 
vesicles  are  each  later  subdivided  into  two,  making,  in  all,  five  vesicles, 
from  which  the  different  parts  of  the  brain  take  their  origin.  The 
epiblastic  tissues  constituting  the  covering  of  the  medullary  tube 
especially  multiply,  so  that  the  walls  of  the  tube  are  greatly  thickened 
and  the  developmg  cells  become  specialized  into  the  pecuHar  component 
elements  that  go  to  make  up  the  central  nervous  system.  This  thicken- 
ing encroaches  on  the  lumen  of  the  tube,  but  a  small  canal  in  the  center, 
and  much  larger  cavities  in  the  brain,  persist  throughout  life;  the  former 

is  called  the  central  canal 
of  the  cord,  and  the  latter 
are  known  as  ventricles. 
These  cavities  are  all  lined 
by  epithelial  cells,  which 
in  early  life  are  ciliated. 

In     normal     develop- 
ment      the       medullary 
groove  is  entirely  cut  off 
from    the    superior    ger- 
minal layer,  from  which 
it  springs.    It  occasionally 
occurs  that  the  groove  is 
not  closed,  and  a  part  or 
even  all  of  it  remains  pa- 
tent ;  under  these  circum- 
stances neither  the  bony 
arches  of  the  vertebrae  nor 
the   posterior    and  upper 
cranial  bones  develop  in 
the    situation   where    the 
groove  fails  to  close.     In 
these  cases  malformations 
of  the  brain  or  cord  result, 
the  character  of  which  de- 
pends   on    the    situation, 
kind,   and  extent  of  the 
areas   of   the  groove   not 
closed  over.     We  possess 
no    accurate   information 
as  to  the  cause  of  these 
conditions;  the  general  aspects  of  teratogenesis  are  discussed  on  page  60. 
Craniorrhachischisis   Totalis,  i— When    the    entire   medullary  groove 
remains  patent,  neither  the  skull  nor  the  vertebrae  close  posteriorly; 
the  resulting  condition  is  called  craniorrhachischisis  totahs.     A  fetus  that 
at  birth  presents  this  malformation  is  found  to  possess,  on  the  dorsal  sur- 
face of  its  trunk,  a  wide,  shallow  depression,  uncovered  by  skin,  occupying 
the  median  line,  which,  passing  upward,  becomes  expanded  over  the 
posterior  part  of  the  head.     In  the  median  Hne  of  this  fissure,  flattened 
>  Given,  "Proceed.  Path.  Soc.  of  Phila.,"  June,  1902.  n.  s.,  vol.  v,  p.  266.     Vur- 
pas  and  Le'ri,  "C.   R.  Acad,  des  Sci.,"  July  20.  1903. 


Fig.  405. — Ckani(irkha(  HisrHisis  Totalis. 

There  is  a  small  amount  of  brain  substance  present  and  a  few  shred;^ 

of  nervous  tissue  in  the  spinal  grove. 


THE     NERVOUS    SYSTEM.  S43 

out  over  the  bodies  of  the  vertebnc.  are  found  varying  amounts  of  a 
dehcate,  soft,  and  very  vascular  tissue,  consisting  of  the  rudiments 
of  the  brain  and  cord;  in  rare  instances  no  nervcnis  tissue  can  be  dem- 
onstrated. In  many  cases,  however,  the  anterior  part  of  the  brain  is 
fairly  well  developed.  The  external  surface  of  the  fissure  is  covered  by 
columnar  epithelium,  which  is  continuous  on  each  side  with  the  sr|ua- 
mous  epithelium  of  the  skin,  and  corresponds  to  the  epithelial  lining  of  the 
central  canal  of  the  cord  and  the  ventricles  of  the  brain.  Between  the 
rudimentarv  nerve  substance  and  the  bodies  of  the  vertebra"  arc  the 
highlv  vascular  tissues  of  the  pia  and  arachnoid,  and,  still  more  deeply,  a 
fibrous  membrane — the  dura;  between  the  arachnoid  and  dura  there  is 
often  a  flattened  cavity,  containing  fluid,  and  corresponding  to  the  sub- 
dural space.  In  total  craniorrhachischisis  the  eyes  project  prominently 
from  the  flattened  skull,  but  generally  neither  they  nor  the  nose  are 
greatlv  displaced.  The  spinal  column  is  always  abnormally  curved 
forward. 

Much  commoner  than  failure  of  the  entire  medullary  tube  to  develo]j 
are  limited  defects  restricted  to  small  areas  of  either  the  cranial  or  spinal 
portions.  These  local  anomalies  can  be  more  easily  understood  from 
an  examination  of  the  spinal  malformations;  and  as  they,  in  a  way,  lead 
up  to  the  more  complex  but  analogous  condition  occurring  in  the  brain, 
thev  will  be  first  considered. 

Rhachischisis  Totalis  (Holorrhachischisis). — In  case  the  entire  spinal 
portion  ot  thc,gr<n)ve  remains  ]Kitent  the  condition  that  results  is  known 
as  rhachischisis  totalis.  With  the  exception  of  the  fact  that  the  brain  is 
not  involved,  this  condition  differs  in  no  way  from  eraniorrhachischisis 
totalis,  and  a  sej^arate  deseri])tion  is  therefore  unnecessar)'. 

Rhachischisis  Partialis  (Merorhachischisis). — When  only  a  part  of  the 
spinal  portion  of  the  medullary  tube  fails  to  close,  the  resulting  condition 
is  called  rhachischisis  partialis ;  this  is  most  frequent  in  the  sacrolumbar 
and  cervical  regions,  but  the  intermediate  parts  are  also  occasionally 
affected.  As  in  total  rhachischisis,  the  rudimentary  spinal  cord  is 
exposed — owing  to  a  failure  of  development  on  the  part  of  the  vertebral 
arches — in  the  situations  where  the  groove  remains  patent,  and  the 
anatomy  of  the  condition  is  essentially  that  of  the  more  pronounced 
malformations.  The  spinal  cord  in  the  affected  area  is  spread  out  on 
the  vertebral  bodies,  forming  an  irregular  layer  of  soft,  red,  and  very 
vascular  tissue,  which  connects  the  two  ends  of  the  normal  cord,  or,  in 
some  instances,  forms  the  termination  of  the  cord  below;  in  many  cases, 
however,  this  intervening  rudimentary  substance  is  present  to  a  very 
limited  degree,  or  may  be  entirely  ab.sent.  When  nervous  structures 
are  present,  they  are  covered  by  columnar  epithelial  cells,  and  lie  upon 
a  membrane  that  corresponds  to  the  pia  of  the  normal  cord.  The 
edges  of  this  pial  membrane  are  usually  exposed  at  the  lateral  margins 
of  the  spinal  sul)stance,  and.  therefore,  intervene  l^etween  the  latter 
and  the  skin  of  the  back.  Near  the  upper  or  lower  margin  of  the  de- 
fective cord,  or  at  both  points,  there  is  a  small  depression,  which  cor- 
responds to  the  closed  end  of  the  central  canal  of  the  normal  cord  beyond. 
Between  the  pia.  on  which  the  undeveloped  cord  lies,  and  the  bodies  of 
the  vertebrae  are  the  arachnoid  and  dural  membranes,  with  the  inter- 
vening spaces  tilled  with  liijuid.  as  in  the  normal  vertebral  canal. 

Myelomeningocele. — When    the    condition   just    described    exists    in 


844  SPECIAL    PATHOLOGY. 

infants  or  children,  especially  if  it  be,  as  is  generally  the  case,  toward 
the  lower  end  of  the  spinal  column,  the  subarachnoid  space  frequently 
dilates  as  a  result  of  the  long-continued  pressure  of  the  contained  fluid  on 
the  delicate  pia,  which,  with  the  rudimentary  cord,  forms  the  external 
wall  of  the  cavitv.  In  the  beginning  the  structures  just  mentioned, 
with  a  few  delicate  strands  of  tissue  from  the  arachnoid,  fomi  the  entire 
outer  wall  of  the  tumor,  but  as  the  swelling  increases  the  neighboring 
skin  becomes  a  part  of  its  external  support.  This  condition  is  tech- 
nically known  as  myelomeningocele.  When  the  myelomeningocele 
is  situated  at  the  end  of  the  cord,  the  tumor  shows  on  its  convex  surface 
a  slight  depression,  which  corresponds  to  the  closed  end  of  the  central 
canal  of  the  cord  previously  referred  to. 

Meningocele. — This  is  another  variety  of  malformation  closely  resem- 
bling in  appearance  the  one  just  considered ;  it,  however,  differs  from  mye- 
lomeningocele, in  that  it  appears  not  to  depend  on  an  abnormal  develop- 
ment of  the  medullarv  part  of  the  tube,  but  is  due  to  a  deficiency  of  the 
bony  wall  of  the  vertebral  column.  Under  these  circumstances  there  is 
sometimes  formed  a  saccular  tumor,  the  walls  of  which  are  composed  of 
the  external  laver  of  the  arachnoid  and  the  dura,  external  to  which  are 
the  soft  parts 'covering  the  particular  area  involved.  Meningocele  is 
most  frequent  in  the  sacral  region,  where  defects  in  the  vertebrae  are 
most  common.  In  rare  instances  the  defect  is  in  the  body  of  the  verte- 
brae, in  which  case  the  sac  projects  forward;  it  is  thus  possible  for  the 
tumor  to  protrude  into  the  abdominal  cavity. 

Myelocystocele  (Hydromyelocele). — When  there  are  deficiencies  in 
the  vertebrse,  saccular  tumors  are  in  rare  instances  developed  having 
their  origin  in  accumulations  of  fluid  in  the  central  canal  of  the  cord.  In 
their  outward  appearance  they  closely  resemble  meningocele,  but,  of 
course,  differ  in  that  the  inner  wall  of  the  tumor  is  composed  of  the 
compressed  substance  of  the  cord.  Myelocystocele  in  most  instances 
occurs  in  connection  with  lateral  clefts  in  the  vertebrae,  and  defects  in 
their  bodies  are  also  often  present.  Shortening  of  the  trunk  is  a  frequent 
consequence.  When  there  is  no  defect  in  the  vertebral  column,  the  cen- 
tral canal  is  sometimes  dilated  as  a  result  of  increased  amounts  of  fluid 
within  (salpingomyelus  ;  hydromyelia)  ;  the  dilatation  may  be  diftuse. 
Meningocele  and  myelocystocele  sometimes  occur  together;  the  con- 
dition is  known  as  myelocystomeningocele. 

Spina  bifida  is  the  common  clinical  term  for  designating  any  of  the 
foregoing  conditions  associated  w^ith  the  formation  of  tumor-Hke  rnasses. 
In  the  condition  called  spina  bifida  occulta^  there  is  no  external  evidence 
of  the  partial  absence  of  the  bony  wall  nor  any  protrusion.  The  con- 
dition is  sometimes  associated  with  an  abundant  growth  of  hair  (hy- 
pertrichosis sacralis),  usually  situated  in  the  sacral  area. 

Malformations  of  the  spinal  cord  without  accompanying  defects  in  the 
vertebrae  are  quite  unusual,  and  are  rarely  of  a  pronounced  character. 
However,  the  cord  is  sometimes  abnormally  short  and  slender  (micro- 
myelia),  and  occasionally  exhibits  partial  duplications  (diastemato- 
myelia).     Asymmetries  also  occur. 

Defects  in  the  nerve-roots  are  comparatively  infrequent. 

Primary  defective  development  of    the  nerve-tracts  has  also  been 

'  Schein,  "Budapest!  Orv.  Ujsag."  1904,  No.  7:  also  "  Gyog^-aszat, "  1904, 
No.  29.     Voelcker.  "Miinch.  med.  Woch.,"  Oct.   13,  1903,  p.  1802. 


THE    NERVOUS    SYSTEM. 


845 


observed;  this  is  of  interest,  in  that  it  may  lietonie  the  starting-point 
of  (iisease  in  later  life. 

An  anomalous  condition  of  the  si)inal  cord,  known  as  heterotopia,  is 
occasionallv  observed;  in  this  abnormality  the  ^^ray  substance  docs  not 
bear  its  normal  relation  to  the  white  matter,  but  is  more  or  less  scattered 
through  it. 

The  malformations  of  the  brain  in  general  corres])onfl  to  those  oc- 
curring in  the  cord;  the  causes,  however,  of  the  various  defects  are  not 
so  well  understood.  In  addition  to  craniorrhachischisis,  which  has  been 
described,  there  is  no  doubt  that  many  of  the  other  cerebral  malfor- 
mations owe  their  origin  to  permanent  patency  of  the  medullary  groove; 
it  is  equallv  clear  that  others  result  from  fluids  accumulating  in  the  cranial 


l-"iG.  406.— Spina  Buipa. 


eavitv  of  the  embryo,  and  causing  rupture  of  the  bony  walls.  There  are 
doubtless  also  other  causes  that  occasionally  produce  these  conditions, 
the  real  nature  of  which,  however,  is  largely  a  matter  of  conjecture. 

Cranioschisis  is  a  condition  produced  by  the  .same  cause  as,  and  closely 
related  to,  craniorrhachischisis,  and  corres[)onds  in  the  brain  to  rhachis- 
chisis  of  the  cord.  Here,  also,  the  cranial  vault  is  to  a  greater  or  less 
extent  absent,  and  on  the  basal  bones  lies  a  reddish  mass  of  tissue,  which 
may  contain  rudimentarv  brain  substance,  or.  more  rarely,  none  at  all 
(anencephalia).  This  reddish  mass  is  covered  l)y  columnar  epithelium, 
which,  as  in  rhachischisis,  becomes  continuous  with  the  surrounding  skin. 
The  base  of  the  skull  is  very  small,  while  the  jaw  and  eyes  project  promi- 
nently, giving  to  the  head  a  ver>'  characteristic  appearance;  for  this 
reason  it  is  sometimes  spoken  of  as  cat-head  or  toad-head. 


846  SPECIAL    PATHOLOGY. 

It  occasionally  happens  that  one  or  more  of  the  gyri  fail  in  a  greater 
or  less  degree  to  develop,  leaving,  at  the  point,  a  depression  that  may 
extend  to  the  ventricle.  These  cavities  of  the  cerebral  cortex  are  most 
common  in  the  central  and  parietal  lobes.  They  have  received  the 
name  of  porencephalia.'  Cavities  very  similar  to  these  may  occur  in 
the  cerebral  cortex  as  the  result  of  disease;  such  condition  is  termed 
pseudoporencephalia. 

Circumscribed  errors  in  development  occur  in  the  skull  analogous  to 
those  that  are  seen  in  the  spinal  column,  but  differing  from  them  in  some 
minor  details.  They  are  most  frequent  in  the  median  line,  and  in  the 
majority  of  instances  are  situated  in  the  posterior  portion  of  the  skull. 

Encephalomeningocele  corresponds  to  myelomeningocele;  it  consists 
of  a  saccular  tumor  of  varying  size  projecting  from  the  skull  at  some 
point — usually  the  occipital  region.  On  section  its  walls  are  found  to 
consist  of  the  outer  layer  of  the  arachnoid,  the  dura,  and  the  skin  and  a 
hernial  projection  of  brain-substance,  which  at  the  apex  of  the  tumor  is 
closely  adherent  to  the  meningeal  coverings,  these  being,  in  turn,  firmly 
united  to  the  skin;  a  small  scar,  or,  sometimes,  a  minute  mass  of  reddish 
tissue,  representing  the  point  where  the  medullary  groove  failed  to  close, 
or  was  last  obliterated,  will  usually  be  found  on  the  external  surface  of 
the  skin,  corresponding  to  the  point  of  adhesion  of  the  membranes  below. 
More  or  less  fluid  is  present  in  the  sac,  usually  between  the  brain  and 
the  adjacent  wall. 

Meningocele. — Should  brain-substance  be  entirely  absent  from  such 
a  saccular  tumor  as  has  just  been  described,  the  condition  is  called 
meningocele. 

Encephalocele. — The  term  encephalocele  is  used  to  designate  those 
saccular  tumors  springing  from  the  skull  that  contain  brain  substance  as 
well  as  the  meninges,  but  no  fluid.  They  are  closely  allied  to  the  con- 
ditions previously  referred  to. 

Accumulations  of  fluids  not  infrequently  occur  in  the  ventricles  of  the 
brain  corresponding  to  myelocystocele,  salpingocele,  and  hydromyelia; 
the  condition  is  known  as  congenital  internal  hydrocephalus.-  This 
abnormality  is,  as  a  rule,  not  compatible  with  health  or  long  life,  but 
infants  so  afflicted  not  infrequently  Hve  for  a  number  of  years,  and 
complete  recovery  sometimes  occurs.  When  an  infant,  Thackeray  is 
said  to  have  been  hydrocephahc,  and  the  recent^  examination  of  the 
brain  of  Menzel,  the  great  German  painter,  has  shown  that  he,  Hke 
Helmholtz,  had  hydrocephalus.  This  condition  is  associated,  when  at 
all  extreme,  with  enlargement  of  the  skull,  greatly  interfering  with  the 
normal  ossification  of  the  bones  composing  it;  in  some  instances  the  intra- 
cranial pressure  becomes  so  great  that  rupture  occurs,  though  immediate 
death  does  not  necessarily  result.  It  has  been  mentioned  that  some  of  the 
malformations  of  the  brain  are  brought  about  by  such  a  rupture  occurring 
/;/  titer o. 

Small  portions  of  the  ventricles  of  the  brain  are  sometimes  separated 
from  the  main  cavities  by  adhesions.  When  this  happens,  the  isolated 
cavity  becomes  greatly  distended,  as  a  result  of  accumulations  of  fluids 

'See  Shirres,   "  Studies  from  the  Royal  Victoria  Hospital,  Montreal,"  vol.  i. 
No.  2,  Jan.,  1902. 

^  See  Spiller,   "  Amer.  Jour,  of  Med.  Sci.,"  July,   iqoa. 

'Berlin  Correspondent  of  "Brit.   Med.  Jour.,"   Feb.    iS,   1905,  p.  384. 


THE  N'EKVorS  SYSTEM.  847 

within;  portions  of  the  fourth  ventricle  iind  the  posterior  horns  of  the 
lateral  ventricles  most  frequently  exhibit  this  abnormality.  A  like 
process  sometimes  orrurs  in  the  fifth  ventricle. 

Cyclopia  (Synophthalmia). — When  arrest  of  development  involves  the 
anterior  part  of  the  brain  and  frontal  area  of  the  skull,  a  malformation 
known  as  cvclopia  s.  metimes  occurs,  mainly  characterized  by  the  fact 
that  there  is  onlv  one  optic  nerve,  both  eyes  beins;  fused  into  one  organ 
that  usuallv  occupies  a  cavity  in  the  center  of  the  forehead;  all  the  face- 
bones  except  the  upper  jaw  may  be  absent.  (See  p.  564. )  The  nose  often 
fails  to  develop;  when  present  it  is  malformed,  and  occu])ies  a  position 
above  the  eve.  Sometimes  the  anterior  portion  of  the  brain  fails  to  divide 
into  two  normal  hemispheres,  and  the  ventricle  is  occasionally  so  dilated 
that  the  l)rain  appears  as  a  large  cyst  (cyclocephalia).  In  less  severe  forms 
of  this  condition  the  two  eyes  may  be  fused  in  i)art  only,  or  may.  without 
union  of  anv  kind,  occupy  the  same  cavity. 

Arhinencephalia. — This  condition,  with  the  exception  that  the  no.se 
is  always  absent,  and  also  the  olfactory  bulbs,  is  practically  identical  with 
cvclopia ;  it  has  been  shown,  however,  that  arhinencephalia  may  exist  with- 
out very  marked  malformation  of  the  eyes.  This  abnormality  is  often 
accompanied  bv  cyclocephaHa ;  absence  of  olfactor\-  nerves;  fissure  of 
the  upper  lip  and  palate;  defective  development  of  the  intermaxillary 
lione  and  nasal  septum;  malformations  of  the  heart,  great  vessels,  and 
auricular  appendages;  umbilical  hernia;  supernumerary  fingers  and  toes; 
and  defects  of  the  diaphragm. 

Microcephaly  may  be  associated  with  arhinencephalia.  It  is  char- 
acterized bv  the  following  peculiarities:  the  brain  is  very  small;  its 
convolutions  are  poorly  outlined  and  much  less  numerous  than  usual ; 
ever>-thing  about  the  brain  attests  the  fact  that  it  is  undeveloped;  the 
skull  is  small  and  its  bones  exhibit  many  abnormalities  of  ossification,  or 
numerous  Wormian  bones  may  be  present.  If  any  or  all  of  the  ventricles 
are  dilated,  the  condition  is  known  as  hydromicrocephaly. 

Partial  hypoplasia  of  the  brain  may  also  occur,  it  is  most  common 
in  the  cerebrum  and  cerebellum,  though  it  may  involve  other  parts  of  the 
central  nervous  system.  If  the  gyri  are  abnormally  small  and  numerous, 
the  condition  is  called  microgyria. 

Hypertrophy  of  the  brain  may  occur,  but  the  condition  is  rare.  Under 
these  circumstances  the  normal  elements  present  in  the  lirain  are  to  a 
greater  or  less  extent  increased  in  number. 

Heterotopia'  of  the  gray  matter  is  a  condition  analogous  to  that 
observed  in  the  cord:  the  gray  matter  is  present  here  and  there  in  the 
white  substance,  giving  it  a  mottled  appearance. 

DISEASES  OF  THE  MEMBR.ANES  OF  THH  HK.MN  .\XD  SPL\.\L  CORD 
Diseases  of  the  membranes  of  both  the  l)rain  and  cord  will  be  con- 
sidered together,  for  not  only  are  they  practically  identical  in  their 
anatomv,  and  verv  closely  related  by  continuity  of  surface,  but  they  are 
affected  alike  in  disease,  and  oftentimes  simultaneously.  As  the  dura 
may  be  diseased  and  the  membrane  that  lies  internal  to  it  may  be  to  all 
intents  and  purposes  normal,  and  vice  versa,  it  b.-.omfs  nrct-<^:irv  to 
consider  their  pathologic  conditions  separately 

•Alice  Hamilton.  "  .\mer    Jour   of  Anat  ."  Scjii 


848  SPECIAL    PATHOLOGY. 

The  cerebrospinal  fluid  surrounds  the  brain  and  cord  and  occupies 
the  normal  cavities  of  these  organs;  normally  it  is  clear,  alkahne  in 
reaction,  possesses  a  specific  gravity  of  1.005  to  i.oio,  and  contains 
traces  of  proteids  and  hydrocarbons.  Recent  studies  in  cyst  diagnosis^ 
have  shown  that  a  microscopic  examination  of  this  liquid  may  be  of 
great  aid  in  diagnosis,  and  that  under  a  number  of  conditions  the  pres- 
sure is  raised.  When  hemorrhage,  either  traumatic  or  pathologic  in 
origin,  involves  the  brain  or  meninges,  erythrocytes  can  usually  be 
demonstrated  in  the  cerebrospinal  flmd.  The  lymphocytes  are  increased 
in  chronic  inflammations  and  tumors,  and  polymorphonuclear  leukocytes 
are  particularly  abundant  in  cerebrospinal  meningitis  and  other  infec- 
tions of  the  meninges  in  which  pyogenic  bacteria  are  present.  It  may  be 
possible  to  demonstrate  specific  organisms  in  the  cerebrospinal  fluid: 
the  effort  is  always  worthy  of  trial  in  suspected  epidemic  meningitis, 
tuberculous  meningitis,  and  other  inflammations  affecting  the  meninges. 
The  parasite  believed  to  be  the  cause  of  syphiHs  (p.  174)  and  the  try- 
panosoma  of  sleeping  sickness  (p.  183)  have  been  found.  The  pressure 
under  w^hich  the  fluid  exists  is  raised  in  certain  forms  of  uremia,  in 
eclampsia,  and  in  some,  but  not  all,  inflammatory  conditions;  nor- 
mally this  pressure  is  between  65  mm.  and  100  mm.  of  water,  and  under 
pathologic  conditions  the  tension  may  rise  to  500  mm.  or  600  mm.,  and 
occasionally  higher. 

The  Dura  Mater. 

Circulatory  Disturbances. — Active  hyperemia  occurs  in  the  dura  in  the 
first  stages  of  inflammation.  Passive  hyperemia  would  be  induced  by 
obstruction,  from  any  cause  whatsoever,  of  the  larger  veins  or  sinuses. 
Hemorrhages  are  usually  the  result  of  injur^^  but  may  occur  in  scurvy, 
and,  occasionally,  in  infectious  diseases.  Sinus  thrombosis-  of  the  cere- 
bral' dura  is,  on  the  whole,  an  infrequent  condition.  It  may  result 
from  infective,  inflammatory,  or  neoplastic  processes  involving  the 
sinuses,  in  which  case  it  is  said  to  be  secondary.  The  most  important 
and  probablv  the  most  frequent  form  of  the  affection  is  that  accompany- 
ing suppurative  lesions  of  the  middle  ear  or  mastoid  and  is  manifested 
by  a  thrombosinusitis  which  often  gives  rise  to  embolic  processes  (see 
thrombosis,  p.  270).  In  individuals  debilitated  by  disease,  and  especially 
in  the  young  and  aged,  the  formation  of  thrombi  within  the  sinuses 
occasionallv  occurs. 

Inflamrnations  of  the  dura,  or  pachymeningitis,  may  be  acute  or 
chronic,  and  suppurative,  fibrinous,  or  productive  in  character. 

Suppurative  pachymeningitis  is  the  most  frequent  variety  of  inflam- 
mation of  the  dura;  it  may  be  acute  or  chronic.  It  is,  in  the  majority 
of  instances,  secondary  to  suppurative  disease  of  the  middle  ear,  but  may 
occur  after  injury  or  disease  of  the  skull  or  vertebrae.  This  form  of 
meningitis  is  sometimes  caused  by  suppuration  of  thrombi  in  the  various 
sinuses,  and  is  rarely  secondary  to  inflammations  of  the  pia  and  arachnoid. 

The  membrane  is  swollen,  owing  to  the  presence  of  increased  amounts 
of  fluid,  and  is  somewhat  reddened.     Microscopically,  the  tissues  are 

1  See  references  on  p.  291,  where  the  subject  of  cytodiagnosis  is  discussed, 
also  consult  Erl,  "Dublin  Med.  Jour.,"  Dec,  1903.  Also  Gordon,  "  Amer.  Med. 5, 
Julv  22,  1905. 

'2  See  Spiller  and  Camp,  "Jour.  Amer.  Med.  Assoc.      Sept.  24,  1904,  p.  68. 


TIIR    NERVOUS    SYSTKM.  849 

found  to  contain  man\'  jJohinorphoiuKlcar  Icukoivtcs,  swollen  ton- 
nectivt'-tissue  colls,  and  \ar\  in,i(  luiinlicrs  of  bacteria. 

Chronic  internal  pachymeningitis '  is  a  |jetuliar  varic-ty  of  inJlam- 
mation  affecting  the  dura  of  the  cranial  cavity;  its  causes  are  not 
understood.  Of  the  dura  the  inner  surface  alone  is  involved,  and  in 
some  instances  the  inflammation  extends  to  the  j)ia  and  arachnoid; 
the  contiguous  bones  of  the  skull  are  sometimes  diseased.  Sometimes 
the  entire  surface  of  the  cranial  dura  is  aflccted,  and  occasionally  the 
condition  is  restricted  to  one  or  more  small  areas,  on  one  or  both  sides  of 
the  brain.  In  the  beginning  stages  of  the  disease  there  forms,  on  the 
internal  surface  of  the  dura,  a  thin  false  membrane,  consisting  of  lihrin, 
in  which  are  many  connective-tissue  cells  and  a  few  leukocytes.  At 
a  later  stage  the  fibrinous  mass  is  permeated  by  blood-vessels;  these 
vessels  verv  frequontlv  rupture,  giving  rise  to  hemorrhage,  and  justifying 
the  name  hemorrhagic  pachymeningitis,  which  is  generally  employed  to 
designate  this  comlition.  The  hemorrhages  are  usually  small,  Ijut  some- 
times are  sufficiently  large  to  exert  considerable  pressure  on  the  brain; 
when  profuse,  they  produce  tumor-like  masses  called  hematomata.  At 
a  later  stage  more  or  less  fibrous  tissue  is  formed  in  the  false  membrane, 
and  the  condition  assumes  the  form  of  a  productive  inflammation. 
Sometimes  the  false  membrane  is,  in  a  manner,  absorbed,  but  the  fibrous 
tissue  remains  as  a  scar.  Discoidal  cysts  containing  blood,  or,  in  old 
cases,  almost  clear  serum,  are  occasionally  observed.  Barratt  does  not 
believe  that  the  process  is  of  bacterial  origin,  but  that  it  depends  upon 
abnormal  formation  of  fibrin  wdthin  the  vessels,  the  walls  of  which 
subsequently  weaken  and  permit  hemorrhage.  Pressure  gives  rise  to 
cortical  atrophy  and  sometimes  cellular  infiltration.  The  disease  is  most 
common  among  the  insane,  and  occurs  in  men  about  twice  as  often  as  in 
women.  If  the  condition  Ije  once  inaugurated,  complete  recover)' 
l)robably  never  occurs;  periods  of  improvement,  followed  by  exacerba- 
tions, commonh'  oc-cur. 

Tuberculosis  of  the  dura  is  secondary  to  tuberculosis  of  the  inner 
membranes,  or  follows  tuberculosis  of  the  bones  of  the  skull  or  vertebrae. 
The  tuljercles  present  the  same  nodular  characters,  with  areas  of 
caseation,  that  are  seen  in  tuberculosis  of  other  parts  of  the  body. 

Syphilis  of  the  dura  alone  is  (juite  rare.  It  occurs  as  local  thicken- 
ings of  the  nicmhranc,  composed  of  collections  of  lymphoid  and  plasma 
cells,  and  an  increase  in  the  amount  of  fibrous  tissue;  at  a  later  stage 
calcareous  deposits  sometimes  fonn  in  these  areas.  The  blood-vessels 
generally  show  evidence  of  endarteritis.  Within  the  affected  tissue 
small  masses  of  caseous  material  are  occasionally  observed. 

Tumors. — Endothelioma  is  the  most  frequent  tumor  of  the  dura  and 
occasionally  attains  considerable  size.  Spindle-cell  sarcoma  and  other 
forms  of  sarcoma  are  sometimes  seen.  Psammoma,  fibroma,  and 
secondan,'  carcinoma  occur;  osteomata  and  enchondromata  have  been 
reported. 

'  Barratt,  'Brain,"  1902,  Part  II,  p.  iSi.  Munro.  "Chicago  Clin.  Recorder," 
Dec,  1902,  p.  381.  Courtney,  "The  Alienist  and  Neurologist."  Feb..  IQ03. 
Hertle,  "Wien.  klin.  Woch.,"  Aug.  6.  1903.  p.  919.  Fischer.  "Zeit.  f.  Heilk.," 
1904,    Bd.    xx\  .    II.  10. 

55 


s50  special  pathology. 

The  Pia  and  Arachnoid. 

Circulatory  Disturbances. — Active  hyperemia  is  produced  b}'  any 
irritant  acting  on  the  membranes.  It  is,  therefore,  of  course,  always 
jirescnt  in  the  V)eginning  of  inflammations. 

Passive  hyperemia  is  the  result  of  thrombosis  of  any  of  the  large 
intracranial  vessels,  and  is  also  produced  by  tumors  and  exudations 
pressing  upon  and  obstructing  the  veins.  Under  these  conditions  the 
hyperemia  may  be  more  or  less  localized.  A  more  general  condition  of 
hyperemia  of  the  passive  kind  is  caused  by  obstructive  diseases  of  the 
heart  or  lungs  that  interfere  with  the  onward  flow  of  the  blood. 

These  abnormal  states  of  the  membranes  are,  of  course,  identified 
by  the  fact  that  there  is  more  blood  present  within  the  meningeal  vessels 
than  is  normal.  The  recognition  of  these  conditions,  even  postmortem, 
is  often  difficult,  for  after  death  the  blood  gravitates  to  the  most  de- 
pendent situations.  If,  therefore,  the  head  of  the  subject  be  placed 
lower  than  the  body  for  any  length  of  time,  the  brain,  on  section,  presents 
an  appearance  of  extreme  congestion.  This  may  also  occur  to  a  limited 
degree  if  the  skull  be  opened  before  the  other  cavities  of  the  body.  An- 
emia of  the  meninges  occurs  in  general  anemic  conditions  and  when  there 
is  narrowing  of  the  vessels  that  carry  the  blood  into  the  parts.  In 
cerebral  ischemia  from  any  cause  the  blood  in  the  meninges  is  less  than  in 
health. 

Edema  of  the  brain  occurs  under  those  conditions  in  which  the  walls 
of  the  blood-vessels  become  so  damaged  that  they  permit  the  fluids  of 
the  blood  to  pass  into  the  surrounding  parts  more  rapidly  than  the 
lymphatics  can  remove  them.  It  is  common  in  inflammations,  and 
as  a  result  of  the  pressure  on  the  vessels  by  morbid  growths ;  an  excess 
of  fluid  is  also  present  in  the  meninges  after  death  from  alcoholism, 
nephritis,  and  chronic  cardiac  disease.  The  condition  is  characterized 
by  the  presence  of  swelling,  and  on  section  more  fluid  exudes  than  is 
normally  the  case;  the  membranes  generally  possess  a  translucent, 
gelatinous  appearance.  If  the  ventricular  plexuses — which,  it  will  be 
remembered,  are  but  extensions  of  the  pia — become  inflamed  or  other- 
wise diseased  in  such  a  way  as  to  cause  increased  permeability  of  the 
walls  of  the  blood-vessels  within  them,  it  must  follow  that  the  quantity  of 
fluids  in  the  ventricles  will  be  increased,  causing  distention  and  enlarge- 
ment of  the  ventricles;  the  condition  is  called  acquired  internal  hy- 
drocephalus.^ Inflammatory  thickenings  due  to  tuberculosis,  syphilis, 
or  other  causes  which  affect  the  membranous  roof  of  the  fourth  ventricle 
and  involve  Magendie's  foramen  or  other  foramina  in  such  a  way  as  to 
prevent  fluid  from  escaping  from  the  ventricles,  lead  to  its  accumulation 
in  these  cavities.  Galatts  believes  that  every  instance  of  hydrocephalus 
not  explained  by  some  other  condition  is  due  to  syphilis.  Some  cases 
are  traumatic.  In  this  connection  it  may  be  remarked  that  in  con- 
ditions giving  rise  to  atrophy  or  necrosis  of  any  part  of  the  brain  the 
space  made  vacant  by  the  process  is  filled  with  fluid.  The  condition 
is  termed  hydrops  ex  vacuo. 

Inflammation  of  the  pia  and  arachnoid  is  called  leptomeningitis,  or 
simply  meningitis.     Like  inflammations  of  the  dura,  it  may  be  acute  or 

'Weber,  "Brain,"  Spring,  1902,  p.  145.  Galatts,"  Wien.  klin.  Woch.,"  1904, 
No.  25.  Southard  and  Roberts,  "Jour,  of  Mental  and  Nervous  Diseases,"  Feb., 
1904,  p.   73. 


THE    N'ERVOUS    SYSTEM.  .S51 

i.liro)iic,  and  siippitt\itivc,  lihriiioits,  or  productive.  Kli(jl(jj,'ically  this 
form  of  meninj^itis  may  be  due  to  pyoj^enic  cocci,  tlic  {jncumococcus, 
anthrax  bacillus,  typhoid  bacillus,  colon  bacillus,  influenza  bacillus, 
bacillus  of  tjlanders,  pneumobacillus  of  Friedlander,  Bacillus  pyocyaneus, 
the  tubercle  bacillus,  actinomyces,  and  a  number  of  other  organisms; 
an  acute  menini,Mtis  of  this  type  occasionally  accomjjanies  syphilis. 
Meninijeal  inthimmation  due  to  injury  (traumatic  meningitis)  f»elongs 
with  this  group;  jt  is  clearly  an  infection.  As  in  inllaniniations  of  other 
serosa^  (p.  45()).  the  acute  forms  are  likely  to  l)e  suppurative  or  fil)rinous, 
or  a  combination  of  the  two,  while  in  the  chronic  cases  fibrous  tissue  is 
produced,  and  the  inflammation  is  conser[uently  spoken  of  as  productive. 
In  a  certain  proportion  of  cases  the  membranes  of  the  brain  and  cord  are 
affected,  but  more  freciuently  the  inflammation  is  confined  to  those  of  the 
cranial  cavity:  rarely,  the  diseased  condition  occurs  in  the  membranes 
of  the  cord  only.  There  is  a  form  of  basic  meningitis  largely  restricted 
to  the  posterior  fossa  and  called  posterior  basic  meningitis.  Still  believes 
that  it  is  specific  and  due  to  a  special  ori^aiiism  which  he  describes; 
Koplik'  has  shown  that  it  may  occur  during  epidemic  cerebrospinal 
meningitis  and  be  due  to  the  Diplococcus  intracellularis  meningitidis. 
In  the  great  majority  of  cases  meningitis  may  be  looked  upon  as  merely 
incidental,  it  being  secondary  to  pathologic  conditions  in  other  parts  of 
the  body,  or  due  to  morbific  influences  that  afifect  the  body  as  a  whole. 
The  exception  to  this  is  the  epidemic  form,  which  is  an  entirely  separate 
and  distinct  disease;  this  variety  will  therefore  be  considered  indepen- 
dently. What  we  may  term,  for  convenience,  incidental  nicningitis 
may  be  divided  into  acute  and  chronic  forms. 

The  acute  form  is  more  common  in  children  than  in  adults.  In- 
vestigations within  recent  years  have  shown  that  in  quite  a  number  of  the 
diseases  that  predipose  to  meningitis  the  same  micro-organism  is  re- 
sponsible for  both  conditions.  Belonging  to  this  group  are  the  menin- 
geal inflammations  occurring  in  connection  with  general  tuberculosis, 
typhoid  fever,  erysipelas,  pneumonia,  and  bubonic  plague;  it  may 
result  from  septicemia,  whether  this  comes  from  septic  wounds,  septic 
puerperal  processes,  the  softening  of  clots,  ulcerative  endocarditis, 
malignant  pustule,  abscesses  or  other  internal  suppurations.  To  this 
list  should  be  added  septic  processes  in  the  vicinity  of  the  brain,  where 
there  is  extension  of  the  inflammation  into  the  meninges  from  contiguity 
of  tissue,  such  as  wounds  of  the  scalp,  erysipelas  of  the  scalp  or  nasal 
cavities,  glanders,  actinomycosis,  disease  of  the  internal  ear  or  mastoid, 
septic  inflammations  of  the  eyes,  caries  of  the  cranial  bones  or  vertebrae, 
and  abscess  of  the  brain  or  cord. 

Inflammation  of  the  meninges  also  occurs  in  connection  with  such 
diseases  as  measles,  scarlet  fever,  smallpox,  and  sunstroke.  Excessive 
mental  work  is  alleged  sometimes  to  act  as  an  exciting  cause,  but  this  is 
doul)tful.  Meningitis  may  also,  of  course,  be  the  result  of  injuries  to  the 
skull.  Lastly,  in  a  certain  proportion  of  cases  meningitis  occurs  without 
antecedent  disease.  When  it  results  as  a  complication  of  sujjpurative 
diseases,  the  same  micro-organisms  that  gave  ri.se  to  the  primary  condi- 
tion are  usually  found  in  the  meninges. 

Morbid  Anatomy. — The  inflammation  may  be  limited  to  some  part,  as 
the  meninges  of  the  base,  or  of  the  convexity  of  the  brain,  especially  if  the 
'"Anier.  jour,   of  Med.   Set.."   Feb.,    1005. 


852  SPECIAL    PATHOLOGY. 

lesion  be  due  to  sunstroke  or  to  local  adjacent  disease,  and  occasionally 
these  parts  are  alone  involved,  even  when  the  process  is  the  result  of 
general  conditions.  The  basal  portion,  except  in  tuberculosis,  is  not  com- 
monly the  only  part  affected.  More  frequently,  evidences  of  the  in- 
flammatory process  can  be  seen  over  the  entire  meninges.  In  the  cord 
the  inflammation  is  usually  widespread. 

Adorbid  Avatouty. — The  appearance  of  the  membranes  differs  some- 
what, depending  upon  whether  or  not  the  process  be  of  a  suppurative 
kind.  In  the  former  class  of  cases,  which  usualh^  follow  suppurative 
diseases,  the  membranes  are  distinctly  reddened,  swollen,  and  opaque; 

>^<  


~A 


Fig.  407. — Section  of  Cerebral  Cortex  and  Meninges  from  a  Case  of  Suppurative  Meningitis. 
A.  Pia-arachnoid  infiltrated  with  pus-cells.     B.  Normal  brain-substance  beneath. 

they  are  bathed  in  a  yellowish- white,  yellowish  or  greenish-yellow,  and 
sometimes  fetid  pus.  The  purulent  collections  are  most  numerous  in 
the  sulci  of  the  brain,  and  may  be  seen  around  the  nerve-roots.  The 
inflammation  sometimes  spreads  to  the  dura.  The  external  surface  of 
the  brain  is  usually  reddened,  and  small  areas  of  softening  are  occasion- 
ally seen.  The  lining  membrane  of  the  ventricle  may  also  be  involved 
in  the  inflammatory  process  (internal  meningitis)  ;  the  fluid  is  often 
greatly  increased  in  the  ventricles.  In  case  suppuration  does  not  occur 
the  conditions  are  practically  the  same,  with  the  exception  that  a  serous 
or  serofibrinous  fluid,  which  may  be  slightly  opaque,  is  present  instead  of 
pus.  On  microscopic  examination  the  vessels  of  the  meninges  are  found 
distended  with  blood,  and  the  affected  tissues  are  infiltrated  with  lym- 
phoid cells  and  swollen  connective-tissue  cells ;  in  the  suppurative  variety 
multitudes  of  polymorphonuclear  leukocytes  are  also  found.     The  sub- 


Till-:    NKkVOUS    SYSTKM.  853 

jaic'iit  brain  is  usually  inliltratetl  with  polyniorplionuclear  leukocytes  and 
lymphoid  cells,  and  the  nerve-fibers  frequently  show  evidence  of  de- 
generative chanj^e,  and  are  sometimes  invaded  by  leukocytes.  The 
same  changes  are  found  in  the  nerve-roots.  Nerve  degeneration,  which 
will  again  be  referretl  to,  and  more  fully  described,  is  evidenced  in  these 
situations  by  necrotic  processes  in  the  white  substance  and  the  formation 
of  irregular  masses  or  droplets,  which  may  or  may  not  Ije  united  to  one 
another  by  thin  filaments  of  myelin.  A  part  of  the  white  substance 
imdergoes  a  fatty  change. 

Method  for  Douonstraliufi  Nerve  Degcucralioiis. — This  may  be  done 
by  the  myelin  stains  of  Weigert,  already  referred  to  (p.  838).  A 
better  method  is  the  following,  which  was  devised  by  Marchi': 

Place  the  specimen  in  Muller"s  fluid  (p.  31),  or  the  solution  of  Orth 
(p.  31),  and  allow  it  to  remain  eight  days  or  longer.  Remove,  and  cut 
into  slices  not  more  than  three  or  four  millimeters  in  thickness.  Put 
these  pieces  into  Marchi's  mixture  (p.  244);  let  the  tissue  remain  in  this 
solution  for  at  least  six  or  eight  days.  It  is  then  removed,  passed 
quicklv  through  alcohol,  and  alcohol  and  ether,  and  is  embedded  in 
celloidin  (p.  42).  Examine  the  sections  without  staining.  The  fat  in 
the  degenerated  nerves  is  stained  black,  while  the  normal  nerves  remain 
nearlv  colorless.  This  method  depends  on  the  fact  that  normal  myelin, 
after  remaining  in  Muller's  solution  eight  or  ten  days,  loses  the  property 
of  being  blackened  by  osmic  acid,  while  any  fat  resulting  from  degen- 
eration still  retains  this  quahty. 

The  term  meningismus-  has  been  applied  to  a  condition  in  which 
the  clinical  svnii>toni.s  all  point  to  meningitis  and  the  autopsy  discloses 
no  evidence  of  meningeal  inflammation.  In  some  of  these  cases  bacteria 
which  ordinarily  give  rise  to  inflammation  are  present.  It  is  believed 
that  the  irritation  produced  by  the  bacterial  toxins  induces  clinical 
phenomena  without  at  the  same  time  giving  rise  to  exudates.  The 
condition  has  been  observed  in  typhoid  fever,  pneumonia,  er}'sipelas, 
and  in  epidemic  cerebrospinal  meningitis.  In  some  cases  the  micro- 
organisms have  been  obtained  by  spinal  puncture  during  life,  and  in  other 
instances  thev  have  been  demonstrated  postmortem.  Birnbaum  calls 
this  peculiar  manifestation,  meningeal  sepsis  without  lesions. 

In  tuberculous  meningitis  the  inflammatory  phenomena  vary  with 
the  number  of  tubercles  and  the  resistance  offered  by  the  tissue  to  the 
development  of  the  process.  Occasionally,  only  a  few  small  nodules 
are  found — generally  in  the  basal  meninges  or  in  the  fissure  of  Sylvius. 
Under  these  circumstances  there  is  no  inflammation  worth  mentioning. 
In  rare  instances  localized  collections  of  such  tubercles  are  present  on  the 
convexitv  of  the  brain,  just  in  front  of  the  fissure  of  Rolando;  this 
varietv  of  tuberculosis  is  called  menitigitis  en  plaque.  Sometimes  the 
tuberculous  form  is  quite  acute,  and  proves  fatal  in  a  few  weeks;  the 
exudate  in  these  cases  often  possesses  a  ])eculiar  jelly-like  appearance. 
The  inflammatory  phenomena  are,  however,  rarely  so  marked  as  in  the 
suppurative  forms;  distinct  tubercles  are  not  formed,  or,  if  so,  they  are 

'  For  discussion  for  artefacts  produced  by  the  Marchi  method  see  Stransky, 
■  Neurolog.  Centralbl,"  July  16,  IQ03,  p.  65^'.  Meyer.  "Centralbl.  f.  Nervenheil. 
u.   Psvch.."  Julv,   1Q03,  voi.    14,   N'o.   7. 

'  Bimbaum.  "Munch,  med.  Woch.."  July  21,  1003.  Staubi,  "Deut.  Arch. 
f.  klin.  Med.."  vol.  82.  Xos.   i   and  2. 


854  SPECIAL    PATHOLOGY. 

ver)'  minute.  On  microscopic  examination  the  appearance  is  much  like 
that  of  nonsuppurative  meningitis.  There  are,  however,  more  marked 
changes  in  the  small  blood-vessels  than  are  usually  found  in  the  ordinary 
inflammations.  The  adventitise,  of  the  small  arteries  especially,  are  in  a 
large  degree  replaced  by  Ivmphoid  and  plasma  cells,  and  a  like  con- 
dition of  the  intimse  is  frequently  found.  A  peculiar  change  in  some  of 
the  vessels  is  that  their  intimae  are  pushed  inward  some  distance  from 
the  muscular  coats,  and  the  space  thus  produced  is  filled  with  fluids  and 
a  few  lymphoid  cells.  This  condition  has  also  been  noted  by  Ohlmacher 
in  meningitis  due  to  the  typhoid  bacillus.  The  collections  of  cells 
around  the  blood-vessels  are  beginning  tubercles,  for  bacilli  may  be 
detected  within  them,  and  occasionally  a  giant  cell  is  seen.  In  chronic 
cases  well-formed  tubercles  with  caseous  centers  are  encountered.  If 
the  inflammatory  process  encroaches  on  the  nervous  tissues  beneath, 
more  or  less  degeneration  results,  and  the  parts  are  infiltrated  with 
lymphoid  cells.  Weill  and  Pehu^  believe  that  tuberculous  meningitis  is 
never  primary;  of  the  sixty-eight  cases  which  they  studied  at  autopsy 
there  was  a  notable  adenopathy  (tuberculous)  in  sixty-one,  and  in  the 
other  seven  manifest  tuberculous  lesions  in  other  parts  of  the  body 
were  present.      In  onlv  ten  cases  did  the  viscera  escape. 

Syphilis  of  the  Meninges.- — Gummata  are  sometimes  found  in  the 
pia-arachnoid  ;  they  occur  as  flattened,  pinkish  or  grayish  nodules, 
which  on  section  are  often  found  to  contain  disintegrated  tissue  in 
which  caseous  material  is  frequently  present.  Around  these  nodules 
there  is  always  a  considerable  increase  in  the  amount  of  fibrous  tissue, 
and  the  blood-vessels  show  evidence  of  obliterative  endarteritis.  A 
general  and  more  acute  syphilitic  inflammation  of  the  meninges  of  both 
the  brain  and  cord  is  sometimes  encountered.  The  appearance  of  the 
meninges  is  much  the  same  as  in  the  acute  tuberculous  form,  and  on 
microscopic  examination  but  little  difference  is  found  in  the  histology 
of  the  two  processes;  however,  evidence  of  obliterative  endarteritis  in 
the  syphilitic  form  is  usually  present  and  the  peculiar  giant  cells  of 
tuberculosis  are  absent.  Syphilis  sometimes  produces  a  chronic  infantile 
meningitis,  in  which  the  membranes  are  opaque,  thickened,  and  infil- 
trated with  lymphoid  cells. 

Chronic  alcoholic  meningitis  results,  as  the  name  indicates,  from 
the  prolonged  and  excessive  indulgence  in  alcoholic  beverages.  The 
meninges  of  the  cerebral  convexities  are  chiefly  affected.  The  process  is 
never  very  marked.  The  meninges  are  slightly  opaque  and  thickened, 
especially  over  the  sulci,  and  along  the  sides  of  some  of  the  vessels  there 
may  be  streaks  of  lymph.  The  microscopic  appearances  are  those  of 
nonsuppurative  meningitis,  though  the  inflammatory  phenomena  are  less 
marked.  Chronic  inflammatory  conditions  of  the  meninges  may  also 
result  from  the  pressure  of  tumors,  foreign  bodies,  etc. 

'  "Lyon  Med.,"  Aug.  9,  1903,  p.  228.  For  discussion  of  the  histologic  changes 
of  tuberculous  meningitis  see  Diamond.  "Trans.  Chicago  Path.  Soc,"  May  13, 
1901.  Also  Armand-Delille,  "Role  des  Poison  du  Bacille  de  Koch  dans  la  Menin- 
gite  Tuberculeuse  et  la  Tuberculose  des  Centres  Nerveux,"      Paris,   1904. 

^  Hirschl.  "Wien.  klin.  Woch.,"  April  28,  1904,  p.  465.  Schaffer,  "  Neurolog. 
Centralbl.,"    Nov.    16.    1904,   p.    1026. 


TMK    NfiKVOUS    SVSTKM. 


855 


Cerebrospinal  meningitis'  is  an  atutt-  iiitftlii'U.sdiscasi'.m'tuTallyoi 
ring  in  epidemics,  and  due  to  the  Diplococcus  intraeellularis  meninj^i 
(p.  1 1 1),  also  tailed  the  meningococcus.  Althougli  coniinunicaM'-  ' 
has  been  considerable  doubt  as  to  the  route 
bv  which  infection  occurred.  It  has  gcner- 
ailv  been  held  that  the  meningeal  lesion  is 
due  to  hematogen(JUS  dissemination  of  the 
organism.  The  studies  of  Maragliano  in- 
dicate that  the  meningococcus  enters  the 
cranial  cavity  from  the  nasal  fossa.  Man- 
doul  and  others  have  succeeded  in  cultivat- 
ing an  organism,  lielieved  to  be  the  men- 
ingococcus, from  the  nasal  mucus  in  cases 
of  meningitis,  and  also  in  healthy  individ- 
uals who  have  been  in  contact  with  possi- 
ble sources  of  infection.  Though  not 
limited  to  any  age,  the  disease  is  most 
fre(iuent  in  individuals  under  twenty  years, 
and  is  especially  common  during  child- 
hood and  adolescence. 

Morbid  AnatO}}iy. — In  those  cases  in 
which  death  occurs  within  twenty-four 
hours  the  meninges  are  merely  reddened; 
on  microscopic  examination  a  few  lymph- 
oid cells  may  be  found  in  the  vicinity  of 
the  vessels,  and  here  and  there  small  hemor- 
rhages into  the  tissues  are  observed. 

In  the  later  stages  the  membranes 
are  intensely  injected,  and  are  covered 
by  purulent,  seropurulent,  and  fibrino- 
purulent  exudations.      In  more  advanced 


cur- 
tidis 


Fig.  408.— Spinal  Coru  anti  Mr..NiN(;ES. 
Transverse  section  showing  distribution  of  the  exudates  in  men- 
ingitis. 
A.   Dura.     B.    Position  of    cTudatc  in  external  pachymeningiti^. 
C.  Kxud:i'-  in  1.  r,t,,!n.ningitis. 


iMO.  409— Past  op  Spinal  Coru  anh 
.Meninges,  Dika  I.aiij  Open  on 
PosTEKioH  Si  Ki\<  k;  Case  or  tpi- 

DKMIC  CkRKIIKUSPINAL   MENINGITIS. 

Ihr  cord  ami  ner\c  rmits  arc  covered  l>y 
a  ihiik  sfnipiirulrni  and  tihrinous 
exudate,  whiin.  a.s  the  pia  .ir.uhni>i>l 
arc  more  involved  than  the  ilura,  i- 
clovly  adherent  to  the  cord. 

'Councilman,  .\lallurv  and  WriKlil.  A  KciM^rl  «.f  tho  Statt-  Board  of  Health 
of  Massachusetts,"  iSyS  E.  G.  and  Mary  flainilton  Williams.  •Jour,  of  Trop. 
Med.,"  iQoo.  Nuthall  and  Hunter.  •'Brit.  Med.  Jour."  Sept.  21.  i«)oi.  Jun- 
dell.  'Nordiskt  .Med.  Arkiv,"  Stockholm,  1901.  Bettencourt  and  Franca.  "Zeit. 
f.  Hvg, "  1904,  tome  xlvi.  p.  403.  Rist  and  Paris.  'Arch.  (ien.  de  Med.  Exp.," 
1904',  No.  S,  449.  Mandoul.  "La  Prcsse  Med.,"  Feh  ii,  1905.  p.  89-  Council- 
man,' "Jour.  Amer.  Med  Assoc,"  April  i,  1905.  Maragliano,  "Gaz.  Osped.  c 
delleClin,"  100;.  No.  10      See  also  Meningococcus,  p.  iii. 


856  SPECIAL    PATHOLOGY. 

cases  the  membranes  sometimes  ])resent  the  pecuhar  jelly-Hke  appear- 
ance commonly  observed  in  tuberculous  meningitis;  this  is  due  to 
the  exudate  becoming  more  fibrinous  in  character.  The  lesions  are 
most  marked  at  the  base  of  the  brain  and  along  the  posterior  portion 
of  the  cord;  nevertheless,  all  parts  may  be  affected.  On  the  cere- 
bral convexities  there  is  usually  more  exudate  in  the  vicinity  of  the 
fissure  of  Rolando  than  elsewhere.  On  microscopic  examination  the 
meninges  are  found  greatly  swollen,  containing  many  multinuclear 
leukocytes  and  enlarged  connective-tissue  cells;  fibrin  is  also  present. 
The  blood-vessels  are  often  thrombosed;  around  some  of  the  vessels  a 
few  lymphoid  cells  are  occasionally  present.  Within  the  pus-cells  many 
of  the  specific  micro-organisms  are  found.  Councilman  recommends 
the  following  method  for  demonstrating  them:  Stain  sections  of  tissues, 
which  have  been  fixed  in  corrosive  sublimate  (p.  34)  in  a  saturated 
solution  of  eosin  (p.  50)  in  water,  for  an  hour.  Wash  in  water,  stain  one 
or  two  hours  in  Unna's  alkaline  methylene-blue  (p.  48),  diluted  nine  times 
with  water.  Wash  with  water.  Dehydrate  in  absolute  alcohol,  clear  in 
xylol,  and  mount  in  xylol-balsam.  The  bacteria  and  the  nuclei  are 
stained  blue,  while  the  tissues  in  general  are  reddish.  In  the  chronic 
cases  the  exudation  is  much  less  in  amount,  being  confined  to  small  areas, 
and  consisting  of  degenerated  pus-cells  and  granular  detritus.  The 
chronicity  of  the  process  results  in  the  meninges  becoming  much 
thickened,  from  the  formation  of  new  fibrous  tissue.  In  this  tissue 
lymphoid  and  plasma  cells  are  found. 

In  the  brain  and  cord  the  vessels  are  injected,  and  the  substance  of 
both  of  these  viscera  is  somewhat  softened  and  edematous.  Punctiform 
hemorrhages  are  occasionally  seen.  Both  the  cranial  and  spinal  nerves 
are  swollen,  reddened,  and  often  infiltrated  with  leukocytes. 

Microscopic  examination  of  the  brain  and  cord  shows  the  blood- 
vessels engorged  with  blood;  the  endothelial  cells  are  swollen  and  in- 
creased in  number,  and  mitotic  figures  are  frequently  observed.  The 
lesions  in  the  brain-substance  are  generally  not  found  below  the  mole- 
cular layer,  though  occasionally  they  extend  much  deeper — even  entirely 
through  the  gray  matter.  The  nervous  tissues  are  more  or  less  infil- 
trated with  pus-cells,  and  the  neuroglia  cells  become  swollen  and  mul- 
tiply. The  ganglion  cells  are  seen  in  all  stages  of  degeneration,  from 
sHgiit  irregularities  in  the  chromophilic  substance  to  its  complete  dis- 
appearance, and  the  final  necrosis  and  disintegration  of  the  entire  cell, 
(Toluidin-blue  or  Nissl's  method,  see  p.  837.)  These  changes  are  not  so 
marked  in  the  cord  as  in  the  brain.  Many  of  the  nerve-fibers  in  the 
brain,  cord,  and  nerve-roots  show  degenerative  changes,  demonstrable 
by  the  methods  of  Marchi  or  Weigert.     (See  pp.  853,  838.) 

Tumors  of  the  Pia-arachnoid. — Sarcomata,  either  of  the  ordinary 
types  or  endotheliomata— especially  the  latter — are  the  most  common 
of  the  new  growths  found  in  the  meninges.  They  form  round  or 
flattened,  soft,  grayish  or  grayish-red  tumors,  which  spread  along  the 
meninges  and  penetrate  the  brain-substance  by  means  of  the  fibrous 
bands  projected  inward  from  the  pia.  Microscopically,  they  show  the 
usual  peculiarities  of  sarcoma  or  endothelioma.  They  occasionally 
occur  as  angiosarcoma,  inyxosarconia,  or  augioinyxosarcoma;  very  rarely 
they  are  pigmented. 

Rarer  forms   of  tumors   of   the   meninges   are   myomata,  fibromata, 


THK    NERVOUS    SYSTEM.  857 

lipomata,  clioiuircuiuita,  ostconuiUi,  and  tfratoiiiata.  Secondary  sar- 
comata and  epitheli(iniata  may  also  occur.  Pcnuoid  cysts  are  some- 
times found.  Cysts  ])roduced  by  cchiuococci  and  cysticerci  arc  some- 
times encountered. 


THE   BRAIN. 

Circulatory  Disturbances. — Anemia  of  the  brain  occurs  as  a  result  of 
general  anemia,  whether  the  latter  be  symptomatic  or  essential.  Any 
condition  causing  cerebral  or  meningeal  edema  lessens  the  amount  of 
blood  contained  within  the  cranial  cavity.  Tumors  and  collections  of 
fluid  in  the  brain  may  also  increase  cerebral  tension  and  proportion- 
ately lessen  the  blood-supply.  When  the  blood-pressure  suddenly  falls, 
as  in  shock,  fainting,  and  allied  conditions,  blood-distribution  is  altered 
and  the  brain  receives  less  than  its  normal  quantity.  Cerebral  anemia 
also  results  from  the  exhaustion  following  acute  febrile  diseases,  and  in 
this  form  is  commonly  due  to  cardiac  weakness.  Local  cerebral  anemia 
may  be  due  to  thrombosis,  embolism,  or  obliterative  disease  of  one 
or  more  arteries,  and  may  be  sufficient  to  cause  atrophy  or  necrosis  of 
the  area  supplied  by  the  affected  vessels.  Tumors,  cysts,  meningeal  hem- 
orrhages, and  inflammator\'  exudates  that  locally  increase  the  pressure, 
proportionately  diminish  the  amount  of  blood  in  the  contiguous  brain 
tissue  upon  which  pressure  is  made. 

Morbid  Anatomy. — The  only  macroscopic  evidence  of  general  cerebral 
anemia  is  the  pallor  of  the  brain-substance.  Microscopically,  the 
smaller  vessels  contain  but  little  blood ;  their  walls  may  be  thickened  and 
hyaline.  The  ganglion  cells  often  contain  vacuoles,  the  tigroid  sub- 
stance stains  indifferently  or  is  fragmented  (tigrolysis),  and  in  advanced 
cases  nuclear  changes  are  present.  In  marked  local  anemia  the  struc- 
tural alterations  are  commonly  more  intense  and  will  be  further  dis- 
cussed when  considering  softening. 

Active  hyperemia  of  the  brain  may  be  the  result  of  over-action  of  the 
heart  or  of  dilatation  of  tlie  capillaries  of  the  brain  as  a  result  of  vaso- 
motor disturbance;  a  sudden  contraction  of  the  arterioles  of  other  parts 
of  the  body  may  also  produce  it.  The  hyperemia  is  local  when  a  large 
branch  of  an  artery  becomes  suddenly  obstructed,  thus  causing  more 
blood  to  flow  through  the  neighboring  branches.  The  brain  is  actively 
congested  in  the  beginning  of  inflammatory  conditions,  such,  for  exam- 
ple, as  arise  from  sunstroke;  in  the  earlier  stages  of  acute  meningitis  the 
blood-vessels  of  the  brain-substance  arc  usually  intensely  engorged. 

Morbid  A)iatomy. — The  l)rain  usually  exhibits  more  or  less  redness 
on  examination,  but  attention  should  again  be  called  to  the  fact  that  the 
presence  or  absence  of  unusual  quantities  of  blood  in  the  brain  or  its 
meninges  is  to  be  regarded  as  furnishing  anything  but  relial»le  evidence 
as  to  the  condition  preceding  death,  as  the  position  in  which  the  cadaver 
has  been  allowed  to  remain  affects  very  greatly  the  quantity  of  blood 
in  any  particular  part.  If,  however,  the  hyperemia  be  due  to  inflam- 
mation, the  area  involved  always  shows  some  redness,  especially  if  the 
condition  be  at  all  advanced.  (Jn  microscopic  examination  the  vessels 
are  sometimes  found  distenderl  with  blood,  and,  if  beginning  inflam- 
mation be  present,  the  usual  evidences  in  the  surrounding  tissue  will  be 
apparent. 


S58  SPECIAL    PATHOLOGY. 

Passive  hyperemia  of  the  brain  results  from  thrombosis  of  the  larger 
venous  sinuses,  or  pressure  u]jon  them  by  tumors,  cysts,  extravasations, 
and  exudations;  pressure  on  the  superior  vena  cava  or  the  innominate 
vein  or  thrombosis  of  thes6  vessels,  may  also  occasion  it.  Congestion  of 
this  type  also  occurs  in  those  diseases  of  the  heart  causing  distention  of 
the  venous  system.  It  is  also  observed,  to  a  limited  extent,  during 
violent  muscular  efforts,  and  is  frequently  marked  when  death  has 
resulted  from  suffocation. 

Morbid  Anatomy. — The  remarks  made  concerning  the  anatomic 
appearances  in  active  hyperemia  apply  equally  well  to  the  condition 
under  consideration.  Microscopically,  the  veins  are  usually  dilated, 
and  they  not  infrequently  rupture ;  in  long-standing  cases  blood-pigment 
is  sometimes  present  in  the  walls  of  the  cerebral  vessels.  Edema  of  the 
brain  mav  result  from  either  variety  of  hyperemia,  but  always  occurs 
if  the  passive  form  persists  for  any  length  of  time.  In  this  condition  the 
arachnoid  spaces  are  dilated. 

General  Pathology  of  the  Ganglion  Cells. ^ — Before  considering  those 
changes  in  the  brain  terminating  in  the  formation  of  gross  lesions  of  its 
substance  it  may  be  well  to  call  attention  to  certain  alterations  in  the 
ganglion  cells  that  result  from  a  large  number  of  different  morbific 
influences.  These  changes  are,  for  the  most  part,  of  such  a  delicate 
character  that  they  were  not  recognized  by  the  older  methods  of  research, 
and,  hence,  their  very  existence  was  not  suspected  until  within  the  last 
few  years.  The  exact  nature  of  these  changes  is  not  clearly  understood. 
They  have  been  regarded  as  parenchymatous  inflammations,  occurring, 
as  they  somtimes  do,  simultaneously  with  inflammatory  conditions  of  the 
surrounding  tissue ;  but  as  they  have  been  observed  in  a  large  number  of 
conditions,  clearly  not  inflammatory,  it  is  very  doubtful  if  they  should 
be  so  considered.  All  these  facts  go  to  show  that  they  are  an  invariable 
result  of  all  influences,  whatever  their  character,  that  act  on  the  body  in 
an  injurious  manner,  and  it  would  therefore  seem  much  more  logical 
to  class  them  with  the  degenerations,  or  possibly  beginning  necroses. 
Moreover,  there  is  nothing  in  the  peculiar  character  of  the  changes  that 
could  stamp  them  as  being  of  an  inflammatory  nature. 

Among  the  most  interesting  of  all  the  more  delicate  alterations  that 
have  been  observed  in  ganglion  cells  are  those  described  by  Hodge  as 
occurring  in  the  ganglia  and  central  nervous  systems  of  animals  as 
the  result  of  long-continued  electric  stimulation,  and  also  extreme 
fatigue.  The  following  well-defined  changes  in  the  nerve-cells  were 
observed:  (i)  Nticleus:  Marked  decrease  in  size.  Change  from  smooth 
and  rounded  to  a  jagged  irregular  outline.  Loss  of  open  reticular  ap- 
pearance, with  dark  stains.      (2)  Cell  protoplasm:    Slight  retraction  in 

'  See  Editorial,  "Jour.  Amer.  Med.  Assoc,"  Jtily  16,  1898,  p.  131.  Larkin  and 
Jelliffe,  "Med.  Record,"  July  8,  1889.  Ladams,  "Nouvelle  Iconographie  de  la 
Salpetriere,"  1900,  Nos.  4.  5,  and  6,  p.  301.  McCarthy,  "Unv.  of  Penna.  Med. 
Bull.,"  Jan.,  1902.  Turner,  "Brain,"  Spring,  1903,  p.' 27.  Ricketts  and  Roth- 
stein,  "Trans.  Chicago  Path.  Soc,"  Feb.  9,  1903,  p  207.  Hirshberg,  "Maryland 
Med.  Jour.,"  July,  ^903,  p.  257.  Marinesco,  "La  Presse  Med.,"  Aug.  26,  1903. 
Spiller,  "Jour.  Med.  Research ,"  Aug. ,  1903,  p.  142.  Wei  senbur  g,  "  Proc.  Path. 
Soc.  of  Phila.,"  Feb.,  1904,  n.  s.,  vol.  vii.  No.  3,  p.  62.  Bailey,  "N.  Y.  Med. 
Jour.,"  July  16,  1904,  p.  100.  Odier,  "Arch,  de  Med.  Exper.,"  July,  1904,  p. 
451.  Laignel-Lavastine  and  Voisin,  "Arch.  Gen.  de  Med.  et  Path.  Anat.," 
March,  1904,  p.  206.  Weber,  "Ltibarsch  and  Ostertag's  Ergebnisse  der  allg. 
Path.  u.  path.  Anat.,"  Neunter  Jahrg.,  I  Ab.,  1903,  p.  212. 


THE    NKRVOUS    SYSTEM.  859 

size  with  vaciKjlation  for  spinal  }.,'anj,'lia;  consi(leral)le  shrinkage  with 
enlargement  of  ])eritellular  lymph-spaces  for  cells  of  cerebrum  and  cere- 
bellum. Lessened  power  to  stain  or  to  reduce  osmic  acid.  (3)  For 
icll-aipsulc,  when  present:  Decrease  in  size  of  nuclei.  (4)  Cells  recover 
their  normal  condition  if  allowed  to  rest,  but  the  process  is  slow.  These 
changes  would  seem  to  have  a  bearing  on  those  neurasthenic  states 
following  worry  and  long-continued  and  unremitting  attention  to  the 
details  of  business. 

More  pronounced  changes  occur  in  the  various  intoxications,  in  the 
acute  diseases,  and  accompanying  the  various  brain  affections.  Berkeley 
has  shown  that  more  or  less  well-detined  alterations  are  produced  in  the 
ganglion  cells  of  the  central  nervous  system  of  animals,  and  even  more 
pronounced  changes  in  the  dendrites  and  gemmulae  of  these  cells,  as  the 
result  of  serum-poisoning  and  ricin-poisoning,  and  from  the  adminis- 
tration of  alcohol. 

Most  marked  changes  in  the  chromophilic  substance  (toluidin-blue 
method)  of  the  nerve-cells  have  been  observed  in  a  large  number  of 
different  conditions  in  man,  such  as  acute  alcoholism,  sunstroke, 
eclampsia,  diabetes,  uremic  conditions,  the  anemias,  all  the  infectious 
diseases,  and  in  the  auto-intoxications. 

The  change  most  frequently  observed  is  fragmentation  of  the  chromo- 
philic masses  of  the  cells  (tigrolysis),  giving  them  the  appearance  of 
being  smaller  and  more  numerous  than  usual ;  if  the  disease-producing 
cause  be  severe,  or  if  it  continues  to  act,  these  V)odies  partly  or  completely 
disappear.  In  rare  instances  the  bodies  unite  with  each  other,  forming 
collections  of  chromophilic  substance  much  larger  than  normal :  all  the 
tigroid  may  unite,  in  which  case  the  entire  cell  is  stained  almost  uni- 
formlv.  In  all  these  conditions  the  quantity  of  pigment  around  the 
nucleus,  if  it  existed  primarily,  may  be  greatly  increased,  or,  if  none  is 
present,  considerable  quantities  may  form.  The  peculiarities  of  these 
pigment  particles  were  referred  to  in  describing  the  histology  of  ganglion 
cells.  (See  p.  837.)  When  the  degeneration  is  pronounced,  the  nuclei 
manifest  a  tendency  to  pass  from  the  center  of  the  cell  to  its 
periphery-,  and  it  has  even  been  asserted  that  they  may  be  partly  or 
completelv  extruded  from  the  protoplasm.  Simultaneously,  the  nuclei 
often  show  a  tendency  to  mitotic  division,  or  they  swell,  and  several 
vacuoles  appear  within  a  single  nucleus;  and  finally  the  nuclear 
outlines  become  indistinct  or  disappear,  the  nucleolus  is  no  longer 
visible,  the  scanty  chromatin  fragments  (chromatolysis),  the  cell  disin- 
tegrates (a  form  of  cytolysis).  and  at  last  disappears,  often  a  prey  of 
}>hagocytic  leukocytes. 

In  sections  stained  by  the  toluidin-blue  method  (p.  S37)  the  processes 
and  axis-cylinders  of  cells  in  severely  diseased  areas  often  appear  broken 
off,  giving  the  cell  a  smooth,  rounded  contour. 

Changes  in  the  Dendrites,  Gemmulae,  and  Neurofibrils. — Unfortunately 
the  method  of  Ooigi  ({>.  t>J,())  does  not  yield  sutViciently  constant  results 
to  be  trustworthy  in  studying  the  degenerative  and  necrotic  changes 
affecting  such  appendages  of  the  ganglion  cell  as  the  dendrites,  gem- 
mulae, and  cvlinder  processes.  So  far,  however,  as  these  studies  have 
been  extended  they  show  that  the  structures  mentioned  participate  in 
the  alterations  occurring  in  the  V)ody  of  the  cell.  The  protoplasmic 
processes  are  often  varicose,  the  gemmula?  scanty  or  absent,  and  some- 


86o  SPECIAL    PATHOLOGY. 

times  fragmented.  The  neurofibril  impregnation  methods  (p.  838)  offer 
sufficiently  constant  results  to  be  of  value  in  identifying  the  nature  of 
finer  changes^  occurring  in  the  ganglion  cells  and  their  processes.  Mari- 
nesco  has  been  able  to  confirm  Cajal's  observation  that  in  tetanus  and 
rabies  the  intracellular  fibrils  are  often  swollen  or  fragmented  and  in 
advanced  cases  are  no  longer  demonstrable.  In  infectious  diseases  and 
other  conditions  in  which  changes  occur  in  the  tigroid  substance  of 
Nissl,  analogous  alterations  are  found  in  the  fibrils.  In  various  forms  of 
insanitv  the  neurofibrils  are  altered,  although  Dagonet  has  shown  that 
in  general  paralysis  many  of  the  fibrils  persist.  Ludlam's  studies 
establish  that  in  mental  disease  irregular  granularity  and  fragmentation 
of  the  intracellular  fibrils  constantly  occur.  Under  the  name  neurono- 
phagia  has  been  described  a  condition  characterized  by  accumulations  of 
cells,  leukocytic  or  neuroglia,  which  encroaches  upon  and  replaces  the 
ganglion  cells.  Such  accumulations  have  been  noted  particularly  in 
rabies,  and  are  thought  by  some  to  be  pathognomonic  of  that  disease. 
In  this  affection  the  changes  seen,  especially  in  the  intervetebral  ganglia, 
consist  of  atrophy  of  the  nerve-cells,  and  proliferation  of  the  capsular 
endothelium,  giving  rise  to  round  cells  that  eventually  fill  the  space 
previously  occupied  by  the  ganglion  cell.  In  addition  to  the  pericellular 
infiltration  the  vessels  of  the  central  nervous  system  are  usually  found 
distended,  mononuclear  cell  elements  accumulate  around  the  numerous 
ganglion  cells,  forming  small  masses  which  have  been  designated  "rabic 
tubercles."  With  regard  to  the  etiology  of  rabies^  we  are  still  in  doubt, 
although  the  infectious  nature  of  the  disease  has  been  clearly  established ; 
Negri  has  recently  described  an  organism,  thought  to  be  of  a  protozoan 
nature,  which  he  believes  to  be  the  cause. 

It  should  not  be  forgotten  that  in  bodies  that  have  undergone 
postmortem  change  the  nerve-cells  exhibit  alterations  closely  resembling 
those  produced  by  disease.  But  at  ordinary  temperatures  abnormal 
conditions  will  not  be,  as  a  rule,  at  all  marked  during  the  first  twenty- 
four  hours  following  death;  if  the  body  be  frozen,  changes  may  not  occur 
even  after  many  days.  The  alterations  consist  in  a  swelling  of  the  cells, 
followed  by  the  gradual  loss  in  staining  power  of  the  chromophilic 
(tigroid)  bodies  and  the  appearance  in  the  protoplasm  of  large  vacuoles; 
the  protoplasmic  processes  often  fragment  and  the  cell  assumes  an  ir- 
regular outline.  The  nucleus  swells  also,  and  its  outlines  become  blurred, 
and  it  may  be  dislodged  and  pass  to  one  end  of  the  cell ;  at  a  later  period 
it  entirely  disappears.  The  nucleolus,  last  of  all,  swells,  disintegrates, 
loses  in  tingibilitv,  and  finally  disappears. 

Secondary  Degeneration  of  Fibers.^ — Over  a  half  century  ago  Waller 

'  Marchand,  "C.  R.  Soc.  Biol.,"  1904,  tome  57,  p.  251.  Dagonet,  "C.  R. 
Soc.  Biol.,"  1904,  tome  57,  p.  298.  Marinesco,  "C.  R.  Soc.  Biol.,"  1904,  tome 
57,  p.  407,  July  9,  1904,  p.  62,  and  March  25,  1905;  also  "Revue  Neurolog.," 
Mav  15,  1904,  p.  405,  and  Aug.  15,  1904,  p.  813.  Bayon,  "Centralbl.  f.  allg.  Path, 
u.  path.  Anat.,"  1905,  Bd.  xvi.  Ludlam,  "Jour,  of  Nerv.  and  Mental  Disease," 
Jan.,  1905.  , 

2  For  a  review  of  the  literature  of  rabies  see  Remlinger,  "  Bulle.  de  I'lnst.  Pas- 
teur," 1904,  tome  ii,  pp.  753  and  793.  Also  Ravenel  and  McCarthy,  "Proceed, 
of  Path.  Soc  of  Phila.,"  1901,  n.  s.,  vol.  iv,  No.  5,  p.  89.  Negri,  "Zeit.  f.  Hyg.  u. 
Inf.,"  vol.  xliii,  No.  3.  Buhlig,  "  Amer.  Med.,"  Nov.  26,  1904.  Luzzani,  "Arch, 
per  ie  Sci.  Med.,"  1904,  vol.  xxviii,  No.  11.  Konradi,  "Centralbl.  f.  Bakt.,"  Feb. 
18,  1905,  p    194.      Maas,  "Miinch.  med.  Woch.,"  1905,  No.  3,  p.  119. 

3  Halliburton,  "  Lancet,"  June  22,  190 1.      Ballance  and  Stewart,  "The  Healing 


TlIU    NKRVOUS    SYSTKM.  86 1 

demonstrakMl  that  if  a  nerve  be  divided,  the  part  distal  to  the  cell  from 
which  the  liber  receives  its  impulses,  degenerates;  this  jirocess  is  called 
Wallerian  degeneration  and  is  of  the  greatest  importance  in  the  study 
and  coinpivlKiision  of  ilegenerative  lesions  afTecting  the  fibers  of  the 
central  ami  ])cripheral  nervous  system.  If  the  cells  in  the  motor  cortex 
be  destroycil,  a  tract  degeneration  follows  the  course  of  the  liber  through 
the  internal  ca])sule,  medulla,  and  cord.  If  the  libers  within  the  internal 
capsule  are  destroyed  by  injury,  hemorrhage,  softening,  or  neoj)lasm, 
those  coming  from  cortical  cells  degenerate  down  to  the  motor  cell  in 
the  cord  with  which  they  communicate;  a  transverse  section  of  the  cord 
gives  rise  to  an  ascending  degeneration  of  nerve-fibers  belonging  to  gan- 
glion cells  lying  below  the  lesion  and  descending  degeneration  develops  in 
the  fibers  coming  from  above  the  injury.  Pressure  of  a  sufficient  degree 
produces  similar  changes.  If  a  ])eri])heral  nerve  be  sectioned,  bruised, 
or  inHltrated  by  a  tumor,  the  distal  |)ortion  degenerates.  In  addition  to 
the  degeneration  occurring  in  a  liber  beyond  the  primary  lesion,  there 
is  also  a  proximal  degeneration  which,  in  the  peripheral  nerves,  extends  to 
the  first  node  of  Ranvier;  there  are  also  slight  changes  in  the  tigroid 
substance  of  the  cell  with  which  it  communicates,  but  these  alterations 
are  inconspicuous,  appear  late,  and  are  far  less  important  than  the 
degeneration  distal  to  the  point  of  injury. 

The  rapidity  with  which  Wallerian  degeneration  occurs  is  largely 
dependent  upon  the  suddenness  of  the  disturl)ance  that  separates  the 
peripheral  from  the  proximal  parts.  When  tumors  infiltrate  or  press 
upon  the  hl)er,  its  conductivity  gradually  disajjpears.  When,  however, 
it  is  sectioned,  torn  apart,  or  in  other  ways  suddenly  injured,  the  changes 
follow  a  fairly  definite  order.  The  studies  of  Halliburton.  Ballance  and 
Ste\vart,  and  others  show  that  for  the  first  three  days  following  the  injur}' 
the  distal  part  of  the  nerve  remains  irritable  and  competent  to  transmit 
impulses.  From  the  fourth  to  the  sixth  day  the  irritaljility  progres- 
sively diminishes,  and,  by  the  end  of  this  time,  fragmentation  of  the 
myelin  becomes  marked.  From  the  sixth  to  the  eighth  day  fatty  changes 
can  first  be  demonstrated  by  the  Marchi  method  (p.  853),  and  this 
microchemic  reaction  persists  for  from  twenty-tivc  to  thirty-five  days. 
The  fragmenting  myelin,  as  a  result  of  necrotic  and  degenerative  changes, 
undergoes  disintegration,  and  is  removed  largely  through  the  interven- 
tion of  phagocytic  cells,  in  which  particles  of  this  substance  may  occasion- 
ally be  demonstrated  as  long  as  the  fifth  month  after  the  reception  of  the 
injury.  Regenerative  processes  may  be  inaugurated  as  early  as  the 
end  of  the  second  week;  these  will  be  further  discussed  in  considering 
repair  of  nerves  at  the  close  of  this  chapter. 

Intracranial  Hemorrhage. — Hemorrhage  within  the  skull  cavity  may 
be  in  the  membranes,  in  which  case  it  is  known  as  meningeal  hemorrhage, 
or  in  the  brain-substance  (cerebral  hemorrhage).  Meningeal  hemor- 
rhage may  again  be  divided  according  to  its  location:    (i)  Extradural 

of  Nerves,"  looi.  Bowlby,  "  Lancet,"  July  26,  1002.  (Jherthiir  and  Monseavix. 
"Rev.  Neurolog.,"  Aug.  ^i,  1902,  p.  812.  Moyer.  "Jour.  Anier.  Med.  Assoc.." 
Oct.  25,  1002,  p.  1043.  Henrikscn.  "Lancet,"  April  11,  igo,^,  p.  1015  Spiller 
and  Frazier,  "Univ.  of  Pcnna.  Med.  HulL,"  June,  1903.  Cattwinkcl  and  Ker- 
schensteiner,  "Lubarsch  and  Ustertag's  Krgehmsse  der  alig  Path.  u.  path.  Anat.," 
Neunter  Jahrg.,  I  Ab..  1903,  p.  9.  Mott,  Halliburton  and  Edmonds,  "Proceed, 
of  Physiological  Soc.,"  March  19,  1904.  Kennedy,  "Brit.  Med.  Jour.,"  Sept. 
24.    1004,  p.  729. 


862  ■  SPECIAL    PATHOLOGY. 

Jieuwrrhage  is  between  the  dura  and  the  skull ;  when  the  hemorrhage  is 
within  the  dura  mater  separating  that  membrane  into  layers,  it  is  called 
(2)  intradural  hemorrhage;  when  the  extra vasated  blood  is  beneath  the 
dura,  the  condition  is  spoken  of  as  (3)  subdural  hemorrJiagc.  Such  hemor- 
rhages are  practically  always  due  to  injury  with  or  without  fracture  of  the 
cranial  bones.  In  hemorrhagic  pachymeningitis  (see  p.  849)  the  hemor- 
rhage is  rarelv  profuse.  The  extended  blood  may,  by  pressure,  influence 
the  cerebral  cortex,  giving  rise  to  degenerative  and  necrotic  processes, 
and  finally  softening.  It  may  undergo  organization,  either  complete  or 
partial,  and  persist  in  the  form  of  cicatricial  tissue.  The  most  important 
form  of  intracranial  hemorrhage  is  that  occurring  within  the  brain- 
substance. 

Cerebral  hemorrhage  includes  all  forms  of  hemorrhage  into  the  brain 
tissue  or  the  ventricles. 

Etiology. — The  most  common  form  of  cerebral  hemorrhage  is  the 
variety  that  occurs  in  individuals  who  are  almost  always  over  forty 
vears  of  age,  and  is  due  to  an  inflammatory  condition  of  the  walls  of  the 
smaller  arteries  in  the  brain,  causing  minute  aneurysms,  which  sub- 
sequently rupture;  this  constitutes  one  form  of  the  clinical  condition 
called  apoplexy.  The  affection  just  named  is  usually  characterized  by 
a  sudden  loss  of  consciousness  and  varying  degrees  of  paralysis,  and  may 
be  due  to  hemorrhage  within  or  upon  the  brain  or  to  embolic  plugging  or 
thrombosis  giving  rise  to  acute  cerebral  softening.  The  form  due  to 
hemorrhage  from  the  meninges,  sometimes  called  meningeal  apoplexy, 
is,  by  most  writers,  distinguished  from  types  depending  upon  intra- 
cerebral lesions.  When  due  to  embolism  or  thrombosis,  it  is  called 
embolic  or  thrombotic  apoplexy  ;  and  when  produced  by  hemorrhage 
within  the  brain,  hemorrhagic  apoplexy.  Hemorrhage  either  from 
the  meninges  or  brain-substance  may  result  from  violence,  and  may, 
of  course,  occur  at  any  age.  In  addition  to  these  causes,  small  puncti- 
form  hemorrhages  into  the  brain  are  occasionally  observed  in  syphilis, 
purpura,  scurvv,  and  leukemia,  and  in  interstitial  nephritis;  such 
hemorrhages  are  also  found,  as  has  been  before  mentioned,  in  meningitis 
and  in  hyperemia  of  the  brain.  Arteriosclerosis  (p.  525),  and  any  form 
of  vessel  degeneration  (p.  520)  in  which  the  vascular  wall  is  weakened, 
are  most  freciuent  causes.  Infective  endocarditis,  or  other  morbid 
process  attended  by  the  presence  of  bacteria  in  the  circulation,  some- 
times causes  infection  of  the  vessel  wall,  as  a  consequence  of  which 
rupture  and  hemorrhage  occur.  It  is  therefore  possible  for  embolic 
processes  to  cause  apoplexy  by  embolism  or  as  a  result  of  hemorrhage. 
The  lesion  resulting  from  bacterial  softening  of  the  vessel  w^all  is  called 
mycotic  aneurysm.'  Lastly,  hemorrhage  sometimes  occurs  from  small 
vascular  tumors. 

Morbid  Anatomy. — In  that  variety  produced  by  disease  of  the  blood- 
vessels the  hemorrhage  is  nearly  always  solitary.  According  to  Charcot 
and  Bouchard,  disease  of  the  blood-vessels  of  the  different  parts  of  the 
brain  occurs  in  the  following  order  as  regards  frequency :  ''  Central 
ganglia,  cortex,  pons,  cerebellum,  centrum  ovale,  middle  cerebellar 
peduncle,  crus  cerebri,  and  medulla  oblongata;  as  might  be  expected, 
this  order  corresponds  closely  to  the  incidence  of  hemorrhage.     The  most 

^  Simmon ds,  "Centralbl.  f.  Chir.,"  Leipzig,  May  18,  1901,  and  "Deut.  med. 
Woch  ,"  May  30,   1901. 


THE    NERVOUS    SYSTEM.  863 

frequent  seat,  however,  is  the  internal  capsule;  this  is  explained  by  the 
fact  that  the  small  vertical  arteries  which  are  distributed  to  this  part, 
namely,  the  lenticulostriate  and  lenticulothalamia,  have  no  collateral 
branches,  are  un<ler  a  his<h  pressure,  and  are  t)ften  diseased ;  these  arteries 
frecjuently  contain  miliary  aneurysms  (p.  525).  One  side  of  the  brain 
is  affected  as  often  as  the  other.  Though  very  rare,  the  hemorrhage 
occasionally  occurs  directly  into  the  ventricles  from  the  choroid  plexuses, 
but  the  l)lood  quite  frecjuently  tinds  its  way  into  the  ventricles  by  burst- 
ing through  from  the  ganglia  that  form  part  of  their  walls.  On  cutting 
into  an  area  of  hemorrhage  there  is  found  toward  the  center  a  mass  of 
clotted  or  semiclotted  blood,  merging  on  every  side  into  the  surrounding 
torn  and  lacerated  tissues,  which  are  often  infiltrated  with  blood  for  cjuite 
a  distance  from  the  center  of  the  lesion,  thus  giving  the  appearance  of 
separate  and  distinct  hemorrhagic  areas  in  the  vicinity.  Jn  rare  in- 
stances almost  the  entire  hemisphere  into  which  the  hemorrhage  occurs 
is  destroyed.  In  the  immediate  area  of  the  hemorrhage  the  nervous 
substance  is,  of  course,  entirely  destroyed,  and  on  microscopic  examina- 
tion contains  only  the  debris  resulting  from  the  disruption  of  the  normal 
structures  of  the  part.  If  the  patient  does  not  succumb  to  the  immediate 
attack,  the  extravasated  blood  begins  quickly  to  undergo  changes;  it 
shrinks,  and  the  color  gradually  fades  until  rtnally  it  is  of  a  reddish-yellow 
hue.  In  the  mean  time  the  presence  of  the  blood  in  the  tissue  results  in 
an  inflammatory  condition  of  the  neighboring  structures,  and  in  the 
formation  of  a  tibrous  capsule  around  the  clot.  In  some  cases  a  capsule 
is  not  produced,  for  the  reason  that  some  of  the  pyogenic  organisms  gain 
entrance  to  the  part,  and  suppuration  results;  the  condition  then  realh- 
becomes  one  of  abscess.  As  the  capsule  forms  around  the  extravasated 
blood,  it  gradually  becomes  smaller,  as  the  result  of  absorption,  but  the 
newly  formed  fibrous  tissue  remains  as  a  scar.  In  some  instances  the 
blood-clot  undergoes  liquefaction,  and,  becoming  encapsulated,  remains 
as  a  cyst;  it  is  thought  that  the  fluid  contained  within  such  cavities  is 
sometimes  absorbed,  and  that  they  may  be  replaced  by  tibrous  tissue. 
As  a  result  of  the  formation  and  subsequent  contraction  of  scar  tissue, 
the  area  in  which  the  hemorrhage  occurs  is  often  markedly  reduced  in 
size.  While  the  quantity  of  newly  formed  fibrous  tissue  depends  on  the 
extent  of  the  hemorrhage,  the  fact  should  be  carefully  notcfl  that  it  is  not 
merely  equivalent  to  the  amount  of  nerve  tissue  destroyed  primarily,  but 
that  it  also  represents  the  sclerosis  consecutive  to  the  secondary'  de- 
generation in  the  nerve-tibers.  the  ganglion  cells  of  which  have  been 
destroved.  or  the  courses  of  which  have  been  interrupted  by  the  lesion. 
The  character  and  extent  of  these  secondary'  degenerations  (p.  8601 
depend,  of  course,  entirely  on  the  situation  of  the  hcmorrliage;  should 
senson.'  fillers  be  damaged,  the  secondary-  degeneration  is  toward  the 
nerve-centers,  while  injury  to  the  motor  fibers  causes  degeneration  from 
the  nerve-centers  toward  the  periphery  of  the  body.  These  degenera- 
tions may  l)e  detected  by  the  method  of  Marchi  (p.  853)  as  early  as 
the  eighth  or  ninth  day  following  the  hemorrhage;  at  a  later  period, 
the  fat  having  disappeared  largely,  the  changes  are  l)est  shown  by  Wei- 
gert's  method.  Later,  compound  granule  bodies  and  corpora  amylacea 
appear  in  the  situations  where  the  degenerative  process  is  going  on ; 
the  neuroglia  increases,  and,  in  the  course  of  time,  a  mass  of  scar  tissue 
replaces    the    degenerated    area.      If    the    brain-substance    be  carefully 


864  SPECIAL    PATHOLOGY, 

washed  from  the  smaller  arteries,  there  may  be  found  here  and  there 
upon  them  minute  saccular  dilatations,  which  are  really  small  aneurysms. 
These  aneurysms  are  the  results  of  a  periarteritis  (see  p.  525)  that 
weakens  the  adventitiae  of  the  vessels,  and  subsequently  causes  the 
atrophy  of  their  muscular  coats.  It  is  the  rupture  of  these  vessels,  the 
walls  of  which  are  weakened,  that  causes  the  hemorrhage.  This  peculiar 
affection  of  the  arteries  should  not  be  confounded  with  atheroma,  which 
is  a  distinct  affection. 

Concerning  the  hemorrhages  resulting  from  injury,  or  those  occurring 
in  connection  with  tumors  and  general  diseases,  there  is  nothing  of  im- 
portance to  be  said  in  addition  to  the  remarks  on  hemorrhage  from 
diseased  blood-vessels.  It  may,  however,  be  observed  that  the  hem- 
orrhages are  often  multiple,  and  are,  as  a  rule,  smaller  than  those  pro- 
duced in  the  usual  way. 

Infantile  meningeal  hemorrhage  may  be  classed  with  those  con- 
ditions in  which  hemorrhage  occurs  directly  into  the  brain-substance,  for, 
although  it  is,  strictly  speaking,  a  result  of  injury  to  the  meningeal  vessels, 
the  effect  is  to  cause  compression  of  the  brain-substance  and  to  produce 
symptoms  that  correspond.  The  blood  is  effused  over  the  convex 
surface  of  the  brain  or  along  the  base;  the  former  is  said  to  be  more 
common  in  foot  presentation  and  the  latter  in  head  presentation;  the 
condition  rarely  follows  normal  labor. 

Occlusion  of  the  vessels  of  the  brain  gives  rise  to  a  process  in  its 
substance  commonly  called  cerebral  softening.  The  most  common 
causes  of  softening  are  thrombosis,  embolism,  and  arteriosclerosis  of 
the  cerebral  vessels,  but,  in  addition  to  these,  it  may  result  from  in- 
flammations of  the  brain-substance,  and  occasionally  occurs  in  old 
age  without  assignable  cause.  Thrombosis  of  the  cerebral  vessels  is  due 
most  commonly  to  obliterative  endarteritis  and  atheroma ;  as  the  former 
of  these  conditions  is  probably  always  syphilitic,  and  the  latter  fre- 
quently so,  it  is  evident  that  syphilis  plays  an  important  role  in  the 
production  of  this  condition.  A  vessel  may  also  be  occluded  by  pressure 
of  tumors,  masses  of  cicatricial  tissue,  and  cysts.  In  peculiar  states  of 
blood  accompanying  child-birth,  in  acute  diseases,  and  in  cancer,  gout, 
tuberculosis,  and  general  malnutrition,  marasmic  thrombi  (p.  273) 
are  sometimes  formed.  Embolism  results  most  commonly  from  diseases 
of  the  endocardium  or  its  valves,  but  may  arise  from  diseased  conditions 
of  the  aorta  or  other  large  vessels;  the  plug  sometimes  comes  from  the 
lung,  and  may  have  originated  in  an  aneurysm  or  morbid  growth.  (See 
Embolism,  p.  278.) 

Morbid  Anatomy. — When  one  of  the  cerebral  vessels  is  occluded, 
the  collateral  circulation  is  rarely  sufficient  to  cause  anything  like  com- 
plete compensation;  in  the  vast  majority  of  instances  the  blood  is 
practically  excluded  from  the  area  supplied  by  the  vessel  involved,  and, 
as  a  result,  the  tissue  in  the  situation  quickly  dies.  Thrombosis  from 
syphilitic  disease  occurs  more  commonly  in  the  larger  vessels.  Em- 
bolism of  the  middle  cerebral  arteries  and  their  branches  is  more  common 
than  in  the  other  vessels,  and  the  vessels  of  the  left  side  are  more  fre- 
quently plugged  than  those  on  the  right.  The  immediate  effect  of  the 
obstruction  of  a  vessel,  either  as  the  result  of  thrombosis  or  embolism, 
is  the  arrest  of  the  blood-supply  to  the  region  supplied.  As  a  result  of 
interference  with  blood  ingress,  the  area  involved  appears  abnormally 
white;  after  twenty-four  or  thirty-six  hours  serum  begins  to  collect  in 


THE    NERVOUS    SVsihM.  ^'15 

the  part,  pushing  the  nerve  elements  apart  and  rcndcrinj;  the  tissue 
edematous;  as  a  result  of  increased  permeability  and  rupture  the  blood 
escapes  from  the  affected  vessels  and  the  region  involved  assumes  a 
yellowish  or  reddish  color,  depending  on  the  cjuantity  of  blood  effused. 
The  nerve  elements  rapidly  undergo  degenerative  and  necrotic  changes, 
and  disintegrate,  forming  a  mass  of  granular  detritus;  by  the  time  this 
stage  is  reached  the  so-called  compound  gra)inle  cells  become  exceedingly 
numerous.  These  bodies  are  probably  leukocytes  exerting  their  usual 
phagocytic  properties.  The  granular  matter  contained  within  the 
protoplasm  of  such  cells  is  derived  from  the  necrotic  erv'throcytes  and 
tissue  elements;  they  also  contain  a  small  (juantity  of  fat.  The  change 
so  far  observed  is  essentially  the  same  as  that  occurring  in  other  forms  of 
infarction,  modified  somewhat  by  the  peculiar  chemic  composition  and 
architecture  of  the  cerebral  tissue;  it  is  essentially  a  necrosis.  In  the 
course  of  a  few  weeks  the  blood-pigment  from  the  degenerated  red  cells 
begins  to  be  absorbed,  and  as  this  process  advances,  the  area,  at  first 
more  or  less  of  a  reddish  color,  becomes  yellowish,  and  finally  white. 
These  stages  correspond  to  the  red,  yellow,  and  white  softening  described 
bv  various  authors.  Red  softening  is  most  marked  in  the  cortex,  where 
the  blood-vessels  are  numerous;  yellow  softening  results  from  the  red  by 
degenerative  changes  in  the  blood-pigment  and  by  its  absorption.  White 
softening,  in  its  purest  form,  generally  occurs  only  in  the  white  substance 
of  the  hemispheres.  The  area  involved  may  be  swollen  and  softer  than 
the  surrounding  normal  tissue;  oftentimes  it  differs  but  little  from  the 
contiguous  healthy  substance. 

In  the  early  stages  inflammatory  reaction  on  the  part  of  the  sur- 
rounding tissue  is  evidenced  by  an  increase  of  the  neuroglia  cells,  and 
the  migration  of  a  few  leukocytes  from  the  normal  blood-vessels  in  the 
vicinity.  In  white  softening  particles  from  the  diseased  region  show, 
when  examined  under  the  microscope,  a  granular  detritus,  nuclei  from 
the  )ieuroglia,  compound  granule  bodies,  and,  at  a  late  stage,  corpora 
amylacea.  The  changes  produced  in  the  nerve-fibers  passing  through 
the  diseased  area  are  the  same  as  those  following  hemorrhage. 

If  the  softened  areas  are  infected  by  any  of  the  putrefactive  or  pyo- 
genic bacteria,  changes  are  induced  that  correspond  to  the  peculiar 
micro-organism  present.  If  the  results  of  the  occlusion  do  not  earlier 
prove  fatal,  in  the  course  of  a  few  months  or  years  the  affected  area 
may  become  encapsulated,  and,  if  the  contents  be  absorl)ed,  a  dense 
mass  of  fibrous  or  gliomatous  tissue  entirely  replaces  it.  It  sometimes 
happens  that  the  solid  parts  alone  are  absorbed  from  the  softened  tissue, 
and  a  cyst  results. 

An  examination  of  the  vessels  of  a  brain  in  which  thrombosis  has 
occurred  usually  reveals  the  pre.sence  of  an  oblitcrative  endarteritis  or 
atheroma  or  other  evidence  of  vascular  disease.  In  the  first-named  con- 
dition the  vessels  exhiljit  hard,  nodular  swellings  along  their  course,  which 
are  the  result  of  an  increase  in  the  thickness  of  their  walls,  and  are  never 
aneurvsmal  in  character.  The  microscopic  changes  consist  of  a  great 
increase  in  the  amount  of  fibrous  tissue  in  the  inner  coat  of  the  vessels, 
and  an  alteration  of  the  same  character  may  be  present  in  the  outer 
tunic.  The  intimae  so  thicken  that  the  lumina  of  the  vessels  are  greatly 
reduced  in  size.  At  the  point  where  the  obstruction  producing  the 
softening  has  occurred,  the  decrease  in  caliber  of  the  vessel  is  so  great 
that  a  thrombus  has  been  produced. 
56 


866  SPECIAL    PATHOLOGY. 

In  case  the  vessels  are  atheromatous  there  will  be  found  some  thicken- 
ing of  the  inner  coats,  and  subsequent  fatty  degeneration  with  the  pos- 
sible formation  of  ulcers  or  calcareous  plates  resembling  those  often  found 
in  other  vessels  so  diseased  (p.  520).  The  obliterative  change  results 
in  this  case  by  the  building  up  of  a  fibrinous  plug  from  an  ulcer,  or  the 
formation  of  like  obstructions  from  the  narrowing  of  the  lumina  of  the 
affected  vessels. 

Thrombosis  of  the  veins  and  sinuses  is  sometimes  encountered;  it 
may  result  from  an  altered  condition  of  the  circulating  blood  or  from 
morbid  processes  primary  in  the  vicinity  of  the  vessels.  Among 
the  former  are  the  blood  states  resulting  from  long-continued  diarrhea, 
suppuration  of  any  kind,  acute  infections,  and  diseases  of  the  lung;  it 
also  occurs  in  the  puerperal  state  and  during  the  course  of  cancer.  The 
condition  is  especially  frequent  in  children.  Belonging  to  the  class  of 
abnormal  conditions  that  produce  thrombosis  by  their  proximity  to  the 
veins  or  sinuses,  are  injury  or  diseases  of  the  bones  of  the  skull,  internal 
ear  diseases,  meningitis,  tumors,  er^^sipelas,  carbuncle,  and  the  presence 
of  foreign  bodies. 

Morbid  Anatomy. — In  the  great  majority  of  instances  the  clot  is 
situated  in  the  superior  longitudinal  sinus ;  this  is  probably  in  a  measure 
due  to  the  fact  that  the  veins  empty  into  it  in  a  forward  direction,  and 
the  current  of  the  entering  blood  is  therefore  opposed  to  the  course  of 
that  of  the  blood  in  the  sinus,  and,  as  a  consequence,  its  circulation  is 
feeble.  The  obstruction  causes  intense  congestion  in  the  blood-vessels 
supplving  the  occluded  sinus,  and  edema  in  the  area  involved;  this  con- 
gested condition  of  the  vessels  may  lead  to  rupture  of  the  smaller  veins, 
so  that  raany  minute  areas  of  hemorrhage  are  often  observed.  Softening 
of  the  cerebral  tissues  occurs  in  the  vicinity  of  the  edematous  and  hem- 
orrhagic spots.  Within  the  vessels  involved  there  may  be  found  a  clot, 
limited  to  one  part  or  occupying  its  entire  extent,  at  first  dark  and  soft, 
but  later  becoming  harder  and  more  or  less  laminated,  as  a  result  of 
the  deposition  of  successive  layers  of  fibrin. 

Infantile  hemiplegia  is  a  condition  the  pathology  of  which  is  not 
clearly  established,  although  there  is  considerable  evidence  indicating 
that  it  is  the  result  of  vascular  obstruction.  It  occurs  in  children, 
following  the  acute  infectious  diseases.  In  connection  with  paralysis  in 
infancy  there  is  an  important  congenital  condition  which  deserves 
special  mention.  According  to  Flechsig,  the  fibers  of  the  pyramidal 
tract  possess  no  myelin  at  birth  and  the  axis-cylinders  begin  to  make 
their  appearance  at  the  end  of  the  fifth  month.  In  prematurely  born 
children  the  pyramidal  (motor)  tract  is,  therefore,  not  developed 
(agenesis).  For  this  reason  children  born  before  term,  especially  at  six 
or  seven  months,  frequently  present  a  spasmodic  state  of  the  limbs 
which  may  be  permanent.     The  condition  is  called  diplegia. 

Inflammations  of  the  brain  (cerebritis,  encephalitis),  like  inflam- 
mations elsewhere,  may  be  acute  or  chronic;  in  addition,  they  mav  be 
simple,  hemorrhagic,  purulent,  or  productive. 

Acute  Inflammations. — The  classification  of  acute  inflammations  of 
the  brain  is  at  the  present  time,  unfortunately,  in  a  state  of  great  con- 
fusion. Authorities  generally  recognize  the  following  varieties:  (i) 
Acute  encephalitis,  the  result  of  injury^;  (2)  simple  acute  focal  ence- 
'  Rawling,  "Lancet,"  1904,  vol.  i. 


THE    NKRVOUS    SYSTEM.  867 

phalitis  (hcmatoj^enous  or  insuhiri,  the  result  ol'  tlic  ;u  utt-  infcilious 
ilisoases;  (3)  acute  hemorrhagic  encephalitis;  (4)  acute  suppurative 
encephalitis. 

It  is  obvious  that  at  the  time  an  injury  occurs  there  is  always  a  strong 
jirol lability  that  the  wound  will  betome  infected  with  some  micro- 
organism, and  to  the  results  of  the  injury  per  sc  there  will  be  quickly 
addeil  the  effects  resulting  from  the  iirescnce  of  the  jjarticular  infectious 
agent  introduced,  and  every  feature  of  the  process  is  accordingly  modi- 
fied; again,  nothing  can  be  more  inaccurate  than  merely  to  say  an  enceph- 
alitis occurs  during  some  infectious  or  septic  process,  since  the  peculi- 
arities of  the  condition  induced  must  vary  as  widely  as  the  diseases  from 
which  they  take  their  origin.  Even  the  term  suppurative  encephalitis 
is  wholly  unscientific,  as  there  are  many  infectious  agents  capable  of 
setting  up  a  process  of  this  kind.  As  much  as  this  condition  of  affairs 
is  to  be  deplored,  in  the  present  state  of  our  knowledge  we  can  perhaps 
do  no  better  than  to  follow  the  classification  just  referred  to.  with  the 
exception  onlv  that  all  those  inflammations  of  a  suppurative  character, 
including  abscess,  will  be  included  under  one  head. 

The  peculiarities  of  an  inflammation  the  result  of  injun,-  will,  of 
course,  depend  on  the  situation,  kind,  and  extent  of  the  wound.  If  no 
infective  agent  be  added,  the  changes  resemble  the  alterations  following 
hemorrhage.  The  nerve  substance  in  the  vicinity  of  the  injury  is 
destroyed,  and  there  is  more  or  less  inflammaton.'  infiltration  of  cells 
into  tlie  part.  A  fibrous  or  gliomatous  wall  may  ultimately  form  around 
the  diseased  area.  The  subsequent  changes  in  the  softened  tissue  and 
the  secondare-  degenerations  ensuing  are  identical  with  those  that  follow 
hemorrhage. 

Simple  acute  focal  encephalitis*  is  a  condition  in  which  the  exciting 
cause  of  the  inflammation  probably  always  reaches  the  brain  by  means 
of  the  circulation.  It  may  occur  in  connection  with  any  of  the  infectious 
diseases,  such  as  influenza,  typhoid  fever,  diphtheria,  and  rabies;  it 
sometimes  results  from  rheumatism,  and  may  follow  sunstroke. 

Etiology. — In  some  cases  the  lesion  is  due  to  the  same  micro-organism 
that  gives  rise  to  the  disease  in  connection  with  which  it  occurs,  and  in 
other  instances  the  general  condition  acts  as  a  predisposing  cause.  ])roduc- 
ing  such  a  lowered  state  of  resistance  on  the  part  of  the  tissues  of  the  brain 
that  other  infectious  agents  hay)pening  to  gain  entrance  to  the  part, 
find  no  difficulty  in  lodging  and  in  producing  the  peculiar  lesions  which 
they  occasion.  It  is  not  impossible,  also,  that  the  soluble  poisons  that 
are  manufactured  in  the  body  in  some  infectious  diseases  may  act 
directlv  as  irritants  to  the  brain  tissues. 

Morbid  Anatowy. — The  lesions  are  generally  scattered  throughout 
the  brain-suV)Stance'as  .small  foci,  which  may  or  may  not  be  macroscopic- 
allv  perceptible.  When  large  enough  to  be  seen,  they  generally  present  a 
red  appearance,  and  are  softer  than  the  neighboring  cerebral  tissue.  The 
areas  are  usuallv  considerably  redder  than  those  of  simple  softening, 
this  being  due  to  the  dilatation  of  the  vessels  in  and  around  the  diseased 
region,  and  to  more  or  less  extravasation  of  blood  into  the  part.  For 
the  foregoing  reasons  inflammation  of  the  brain  was  long  confounded  with 

•  Bauche.   "  Xeurolog.   Centralbl,"    Veh.    i.    1903.  p.    100.       Brooks.   "Med. 
News."  AuR.  S    1903,  p.  241.     Bullard  and  Siim,  "Boston  Med.  and  Surg.  Jour. 
Dec    15.  1904. 


868  SPECIAL    PATHOLOGY. 

softening,  with  which  it  presents  many  points  in  common.  At  a  later 
stage,  indeed,  it  may  be  impossible  to  distinguish  between  them,  for  the 
extra vasated  blood  is  gradually  absorbed,  or  its  coloring-matter  so 
modified  that  the  area  becomes  pale.  During  the  period  of  acute  inflam- 
mation sections,  when  examined  microscopically,  show  distention  of  the 
blood-vessels,  small  focal  hemorrhages,  and  accumulations  of  lym- 
phoid cells  around  the  vessels.  At  a  later  stage  there  are  many  larger 
cells  that  appear  to  be  derived  from  the  connective  tissue  or  neuroglia  ; 
there  are  also  many  plasma  cells.  The  nerve-cells  and  nerve-fibers 
manifest  necrotic  and  degenerative  changes.  If  the  area  be  small,  it  is 
not  improbable  that  practical  restitution  to  its  normal  condition  may 
occur;  but  if  larger,  the  most  favorable  result  that  can  be  anticipated  is 
the  formation  of  a  cyst  or  a  small  scar,  which  replaces  the  tissue  involved. 
Adhesions  of  the  meninges  to  the  cortex  are  frequently  found. 

Acute  hemorrhagic  cerebritis^  is  a  rare  affection  probably  due  to  a 
number  of  causes,  although  in  many  cases  the  etiology  can  not  be  de- 
termined. Twentv  years  ago  Leichtenstern  suggested  that  the  process 
was  of  infective  origin,  and  succeeding  observations  have  strengthened 
this  view.  Considerable  doubt  is  entertained  as  to  whether  there  is 
any  essential  difference  between  the  acute  simple  or  focal  encephalitis 
and  the  lesion  at  present  under  discussion;  the  presence  or  absence  of 
hemorrhage  depends  upon  a  number  of  factors,  and  it  is  not  improbable 
that  the  same  causes  may  induce  either  form.  A  number  of  bacteria 
have  been  identified  in  lesions  of  acute  hemorrhagic  cerebritis ;  Southard 
and  Keene  have  induced  similar  changes  in  guinea-pigs  by  experimental 
inoculation  with  the  Staphylococcus  pyogenes  aureus.  Hoppe  believes 
that  it  frequently  follows  measles,  and  less  commonly  typhoid,  scarlet 
fever,  diphtheria,  and  influenza;  trauma  is  also  a  cause.  In  some  cases 
both  brain  and  spinal  cord  are  involved — encephalomyelitis  haemor- 
rhagica.  There  is  an  intimate  relation  between  the  condition  and 
cerebral  softening,  although  in  the  latter  the  lesions  are  much  larger. 
The  centrum  ovale  is  said  to  be  the  part  of  the  brain  principally  involved ; 
it  is  locally  or  diffusely  softened,  of  a  pinkish  color,  and  contains  numer- 
ous minute  hemorrhages.  The  pia  is  also  injected.  The  blood-vessels 
of  the  white  substance  are  seen  to  be  distended  with  blood  when  examined 
microscopically,  and  there  are  slight  evidences  of  degeneration  of  the 
nerve-fibers  in  this  situation.  Hemorrhagic  foci  are  frequent,  areas  of 
leukocvte  accumulation  numerous  and  generally  small.  The  nerve-cells 
of  the  cortex  are  normal,  or  but  slightly  changed;  the  alterations  in  these 
bodies  are  those  usually  accompanying  infections  and  possess  nothing 
peculiar  to  this  affection. 

Polioencephalitis  is  an  acute  inflammatory  condition  affecting  the 
motor  nuclei  of  the  brain;  when  the  centers  for  the  third,  fourth,  and 
sixth  nerves  are  involved,  the  condition  is  called  polioencephalitis 
superior;  when  the  nuclei  of  the  seventh  to  the  twelfth  nerves,  inclusive, 
are  affected,  the  term  polioencephalitis  inferior  is  applied;  in  some 
instances  the  anterior  cornua  of  the  cord  are  also  affected,  justifying  the 
name  polioencephalomyelitis.     The  ganglion  cells  of  the  affected  area 

'Hoppe,  "Jour,  of  Nerv.  and  Ment.  Dis.,"  Sept.,  1902,  p.  524.  Straussler, 
"Jahrb.  f.  Psychiat.  u.  Neiirolog.,"  1902,  vol.  xxi,  p.  253.  Hinsmans,  "Berl. 
klin.  Woch.,"  Jan.  23,  1905.  Southard  and  Keens,  "Amer.  Jour,  of  Med.  Sci., " 
March,    1905,  p.  474. 


TIIH    NERVOUS    SYSTEM.  869 

are  swollen,  the  tit,'roid  and  nuclear  stainable  substances  are  altered,  the 
axones  and  dendrites  swollen  and  fragmented,  and  leukocytic  accumula- 
tion in  the  contiguous  tissue  sometimes  markeil;  hemorrhages  also  may 
be  present.  When  affecting  the  nuclei  f)f  the  bulb,  this  condition  con- 
stitutes the  anatomic  basis  of  acute  bulbar  paralysis.  If  the  patient 
survive,  sclerosis  ])rol)ably  follows. 

Suppurative  Cerebritis.' — By  far  the  most  frequent  and  important 
of  all  the  inllammatory  conditions  affecting  the  brain  are  those  of  a 
suppurative  character.  The  disease  may  occur  as  a  complication  of  any 
acute  infective  process,  such  as  erysipelas,  pneumonia,  cerebrospinal 
meningitis,  typhoid,  scarlet  fever,  and  even  influenza.  It  is  frequently 
observed  in  conditions  accompanied  by  the  presence  of  pyogenic  cocci  in 
the  circulating  media  of  the  body.  Metastatic  cerebral  abscesses  occur 
in  pyemia,  septicemia,  endocarditis,  phlebitis,  with  or  without  throm- 


Fic.  410. — Section  of  Himax  Brai.v  I.vcludinc  Wall  or  Cf.rkbral  .\bscess. 
a.  a.  Periphery  of  abscess;  necrotic  tissue  containing  pus-ccILs  and  granular  <lotritus.     b.  Wall  cont.Tining  repara- 
tive elements,     c.  More  or  less  normal  brain-substance.     (Queen  obj.,  f-inch;  oc.,  B.) 

l>osis,  and  suppurations  of  distant  parts.  But  at  the  present  time  more 
common  than  any  of  these  causes  is  the  direct  or  indirect  extension  of 
suppurating  processes  to  the  brain-substance  from  neighboring  struc- 
tures, such  as  occurs  in  middle-ear  disease,  chronic  diseases  of  the  nose, 
caries  of  the  bones  of  the  skull,  and  suppurative  lesions  of  the  meninges. 
The  most  frequent  cause  is  a  suppurative  process  affecting  the  middle 
ear  or  mastoid.  Ehrnrooth  has  shown  experimentally  that  lilows  on 
the  head  increase  the  susceptibility  of  the  cerebral  tissues  to  infection 
by  bacteria  circulating  in  the  blood. 

The  most  frequent  organisms  present  in  these  conditions  are  the 
Streptococcus  pyogenes,  the  Staphylococci  pyogenes  albus,  aureus,  and 

'Clayton,  "  Phila.  Med.  Jour.,"  March  2.  1901.  Ehrnrooth.  "Arl>cit.  a  d. 
Path.  Inst.  Helsingsfors, "  1902.  Abth.  I.  p.  101.  Hoppe.  "Jour  Amcr  Med. 
.Assoc.."  March  14,  1903,  p.  702.  Kolpin,  "Deut.  Zeit.  f.  Nervenheilk  ."  1904. 
Bd    25.  p.  465.     Fauvel,  Th^se  de  Paris,  1904,  No.  189. 


870  SPECIAL    PATHOLOGY. 

citreus,  pneumococcus  and  the  Bacillus  pyocyaneus;  actinomyces  are 
also  occasionally  observed;  the  oidium  albicans  has  been  found,  and  other 
organisms  are  sometimes  the  cause. 

Morbid  Anatomy. — When  the  organisms  producing  the  disease 
enter  the  brain  by  means  of  the  circulation,  numerous  minute  foci  of 
inflammation  usually  occur;  macroscopically,  these  resemble  in  every 
way  the  areas  found  in  the  simple  acute  form  of  cerebritis.  When 
the  infection  comes  from  neighboring  structures,  it  generally  extends 
by  continuity  of  surface  to  one  part  of  the  brain  alone,  and  there  occurs, 
as  a  consequence,  a  localized  inflammation  at  the  infected  point  only. 
When  the  diseased  area  is  extensive,  it  is  commonly  called,  when  situated 
in  the  cerebrum,  cerebral  abscess,  and,  when  the  cerebellum  is  affected, 
cerebellar  abscess.  The  cerebrum  is  involved  about  four  times  as  fre- 
quently as  all  the  other  parts  together;  next  to  the  cerebrum  the  cere- 
bellum is  most  frequently  affected.  The  typic  brain  abscess  usually 
contains  a  collection  of  yellowish  or  greenish,  often  fetid,  pus,  which,  in 
addition  to  polymorphonuclear  leukocytes,  is  loaded  with  the  granular 
debris  resulting  from  necrosis  and  disintegration  of  the  nervous  struc- 
ture; in  acute  cases  bacteria  are  present  in  large  numbers;  when  the 
abscess  has  persisted  for  some  time,  microorganisms  are  often  scanty 
or  even  absent.  The  walls  of  the  abscesses  are  irregular;  often  there 
are  several  abscesses  near  one  another,  connected  by  small  sinuses. 
The  surrounding  tissue  is  swollen  and  pinkish  in  color;  if  the  abscess 
be  old,  it  is  not  infrequently  surrounded  by  a  more  or  less  well-defined 
capsule  of  fibrous  tissue. 

Microscopically,  the  walls  of  the  abscesses  show  degenerating  nerve- 
cells  and  nerve-fibers,  an  increase  in  the  neuroglia  cells,  and  infiltrating 
these  areas  of  necrotic  and  disintegrating  tissue  are  multitudes  of 
polymorphonuclear  leukocytes  (pus-cells),  which  have  migrated  from  the 
surrounding  engorged  blood-vessels;  enlarged  connective-tissue  cells, 
lymphocytes,  and,  especially  if  the  process  be  subacute  or  chronic, 
numerous  plasma  cells  are  also  found.  The  capsules  of  very  old  abscesses 
sometimes  undergo  calcareous  change,  and,  in  rare  instances,  the  con- 
tents may  be  similarly  affected. 

Chronic  Encephalitis. — But  little  is  known  of  the  chronic  inflamma- 
tory conditions  affecting  the  brain-substance  alone,  such  lesions  being 
apparently  very  rare.  It  is,  however,  quite  conceivable — and  even 
probable — that  acute  inflammatory  processes,  especially  those  of  a 
nonsuppurative  character,  may  in  some  instances  become  subacute  or 
chronic.  Cases  have  been  recorded  in  which  there  was  postmortem  evi- 
dence of  such  conditions,  but  it  was  impossible  to  say  whether  the 
cerebritis  began  as  a  chronic  process  or  followed  an  acute  inflam- 
mation. The  macroscopic  changes  are  slight  or  wanting  in  chronic 
cerebral  inflammations ;  microscopically  evidences  of  slight  inflammation, 
and  sometimes  small  areas  containing  an  increased  amount  of  newly 
formed  fibrous  or  gliomatous  tissue  are  present. 

Chronic  Meningo-encephalitis.^ — This  is  a  disease  characterized  by 

'  Alzheimer,  "  Histologische  und  Histopathologische  Arbeiten  uberdie  Gross- 
himrinde  mit  Besonderer  Berucksichtigung  der  Pathologische  Anatomie  der 
Geisteskrankheiten.  "  Herausgegeben  von  Frantz  Nissl,  vol.  i.  Halliburton,  "Lan- 
cet," June  22,  1901.  Soukhanoff  and  Gannouchkine,  "Arch,  de  Neurol.,"  Sept., 
1902,  vol.   14.      Folotchinoft",  "Travaux  de  la  Clinique  des  Maladies  mentales  et 


THE    NERVOUS    SYSTEM.  87I 

clironic  intlainniatioii  of  the  l)rain-sul)St:ince  and  meninges,  giving 
rise  to  gradual  impairment  of  the  mind  and  to  general  paralysis;  the 
condition  is  known  clinically  as  dementia  paralytica,  or  paresis. 

The  disease  seems  to  have  sonic*  almost  constant  connection  with 
svphilis,  since  in  about  seventy-tive  per  cent,  of  all  cases  there  is  a  history 
of  an  antecedent  specific  infection;  traumatism,  lead-poisoning,  alco- 
holism, and  prolonged  mental  strain  have  also  been  thought  to  be  pre- 
disposing causes.  The  anatomic  changes  and  clinical  phenomena 
strongly  support  the  view  that  the  affection  is  due  to  a  toxemia,  the 
exact  nature  of  which  remains  obscure. 

Morbid  A}iatoi)iy. — The  lesions  observed  in  this  affection  vary  con- 
siderablv,  but  those  most  commonly  noticed  are  cortical  atrophy, 
especially  of  the  frontal  lobes  of  the  cerebrum,  thickening  of  the  dura, 
with  the  formation  in  some  cases  of  a  membrane  on  its  inner  surface,  and 
condensation  and  opacity  of  the  pia,  which  is  thickened  and  abnormally 
adherent  to  the  brain-substance. 

Microscopically,  small  collections  of  lymphoid  and  plasma  cells 
surround  and  form  mantles  over  the  blood-vessels,  the  walls  of  which 
constantly  show  more  or  less  thickening,  particularly  of  the  adventitiae. 
Destruction  of  many  nerve-cells  of  the  cortex  occurs,  and,  as  a  con- 
sequence, degeneration  of  the  axones  that  pass  from  them;  these  de- 
generations mav  be  traced  downward  through  the  brain  and  cord.  The 
tangential  nerve-fibers  lying  in  the  molecular  layer  are,  in  severe  cases, 
almost  entirely  destroyed.  The  protoplasmic  processes  of  these  cells 
are  similarly  affected.  '  Along  with  these  changes  there  is  considerable 
fonnation  of  fibrous  tissue  in  and  around  the  vascular  processes  passing 
into  the  brain  from  the  pia.  The  neuroglia  cells  are  greatly  increased  in 
number,  and  the  neuroglia  fibers  are  sometimes  thickened.  The  mem- 
branes show  the  usual  microscopic  evidences  of  chronic  inflammation. 
All  these  morbid  changes  in  the  blood-vessels,  neuroglia,  and  fibers  lead 
to  atrophv  of  the  brain;  the  convolutions  become  flattened  and  shrunken; 
the  weight  of  the  organ  is  much  less  than  normal.  The  most  marked 
alterations  are  in  the  motor  area  and  in  the  frontal  lobes.  The  nerve-cells 
of  the  cord  are  often  the  seat  of  marked  degenerative  changes.  The 
meninges  of  the  cord  are  also  much  thickened ;  these  changes  are  espe- 
cially marked  in  the  posterior  portion  of  the  cervical  and  dorsal  cord, 
giving  rise  to  pressure  on  the  sensor}'  nerve-roots,  and  thereby  often 
causing  considerable  pain.  Degeneration  of  tracts,  especially  of  the 
posterior  and  lateral  columns,  has  been  observed  in  a  large  number  of 
cases.  The  proteid  content  of  the  cerebrospinal  fluid  is  usually  increased, 
and 'the  studies  of  Siemerling  and  others  have  shown  that  there  is  an 
almost  constant  lymphocytosis  of  this  liquid,  and  that  during  periods  of 
notable  clinical  ac^tivity  tlic  lymphocytes  are  most  abundant. 

Syphilis  of  the  central  nervous  system,'  exclusive  of  the  parasyphilitic 

nerveuses  a  Saint- Peters bourg,"  IQ02,  fiisc.  i.Pp-  1-210.  Lawrence,  "Jour,  of 
Nerv.  and  Mental  Dis.."  Dec.  IQ03.  p.  754  Diefendorf,  "Amer.  Jour,  of  Med. 
Sci,"  Dec,  190^,0.  1047.  Klipjicl.  "La  Sem.  Mtf-d,"  Aur.  5.  iQo.^.p.  255.  None, 
"Fortschr.  d.  Meci.,"  1904.  No.  2S.  Siemerling.  "Bcrl.  klin.  Woch.."  1904,  No. 
21.  De  Buck.  "  Bulle.de  la  Soc  deM6d.  Mont,  dc  BclRifiue."  Sept.,  1904.  Rol>crt- 
son,  "  Brit.  Med.  lour."  Oct.  24.  1903.  p.  106:;.  Cazcncuvc,  Th^e  de  Bordcau, 
1904.  Curion,  ■Nouv.  iconographie  de  la  Salp^tri^re,"  1905,  No.  5.  Marchand, 
*'La  Presse  M6d.."  .Vpril  8.   1905.  P-  217. 

'  Migazzini,   "Monatsch.  f.  Psychiatry  u.  Neurol."  March.  1902.      Ingclrans. 


872  SPECIAL    PATHOLOGY. 

affections  (p.  180),  occurs  in  about  two  per  cent,  of  all  cases  of  acc|uired 
syphilis.  In  the  congenital  form  of  the  disease  malformations  of  the 
brain,  internal  hydrocephalus,  and  imperfect  development  of  the  cortex 
are  not  infrecjuently  present;  such  patients  are  also  liable  to  the  mani- 
festations of  acquired  syphilis.  The  lesions  of  lues  may  be  restricted  to 
the  brain,  or  to  the  cord,  but  in  most  cases  both  organs  are  involved. 
The  toxin  produced  by  the  infecting  organism  exerts  a  deleterious  in- 
fluence on  both  motor  and  sensory  neurones  throughout  the  cerebro- 
spinal axis,  and  as  these  alterations  are  rarely  exactly  the  same  in  any 
two  cases,  it  is  apparent  that  the  morbid  anatomy  and  clinical  manifes- 
tations of  the  disease  often  fail  to  conform  to  a  definite  series  of  pheno- 
mena. Aside  from  the  specific  toxic  effect  of  the  poison  on  the  function- 
ating elements  of  the  brain  and  cord,  the  changes  in  the  blood-vessels  and 
meninges  indirectly  influence  the  nutrition  of  the  brain  and  cord.  The 
alterations  of  meningoencephalitis  have  already  been  considered  (p.  870). 
Obliterative  endarteritis  affecting  particularly  the  branches  in  the 
Sylvian  area  is  frequently  observed.  In  this  manifestation  proliferative 
changes  occur  in  the  subintimal  layer  of  the  affected  vessels,  followed  by 
alterations  in  the  endothelium,  hyaline  or  fibro-hyaline  transformation 
of  the  new  tissue,  reduction  in  vessel  lumen  and  therefore  diminished 
blood-carrying  capacity  and  starvation  of  the  tissues  supplied  by  the 
affected  arteries.  Periarteritis  and  atheroma  also  occur.  Thrombosis 
and  softening  are  sometimes  observed.  The  most  frequent  form  of 
syphilis  of  the  cord  is  a  meningomyelitis  characterized  by  some  softening, 
congestion,  and  edema,  often  focal,  or  limited  to  small  areas,  especially 
in  the  lumbo-thoracic  region.  Histologically  the  affected  areas  are  the 
seat  of  lymphocytic  accumulation,  degeneration  of  the  myelin,  and 
swelling  of  the  axis-cylinders ;  proliferation  of  the  glia  occurs  early  in  the 
process,  but  is  generally  conceded  to  be  secondary  to  cell  infiltration, 
and  degenerative  and  necrotic  changes.  The  pia  and  arachnoid  are 
frequently  thickened,  infiltrated  with  lymphoid  and  plasma  cells,  and  in 
some  cases  there  is  a  notable  exudate.  Obliterative  changes  in  the 
vessels  are  similar  to  those  already  described  as  occurring  in  the  brain. 
When  the  condition  has  persisted  for  a  considerable  time,  the  areas  of 
primary  infiltration  are,  by  proliferation  of  the  neuroglia,  converted 
into  sclerotic  areas,  from  which  secondary  degenerations  commonly 
arise. 

Gumma  of  the  brain  varies  in  size  from  a  microscopic  collection 
of  lymphoid  cells  and  fibrohyaline  tissue  to  masses  5  cm.  to  10  cm. 
in  diameter.  In  gross  gummata  the  consistency  is  rarely  uniform, 
the  periphery  being  soft,  succulent,  and  vascular,  and  the  center  dry, 
firm,  relatively  bloodless,  pale,  and  hyaline  or  containing  yellowish 
caseous  areas.  Histologically  the  gumma  (p.  179)  is  composed  of  masses 
of  lymphoid  and  plasma  cells,  spindle-shaped  and  stellate  connective- 
tissue  elements,  and  a  fibrohyaline  matrix.  The  younger  cell  masses  are 
at  the  periphery  and  the  fibrous  or  fibrohyaline  and  caseous  material 
near  the  center.  Giant  cells  are  occasionally  present,  but  are  incon- 
spicuous.    It  is  probable  that  gummata  may  be  infected  by  tubercle 

"Echo  Med.  du  Nord,"  April  3  and  10,  1904.  Hirschl,  "Wien.  klin.  Woch.," 
April  28,  1904,  p.  465.  Ogilvie,  "  Brit.  Med.  Jour.,"  July  16,  1904,  p.  140.  Mott, 
"Practitioner,"  July,  1904,  p.  55.  Barrett,  "Amer.  Jour,  of  Med.  Sci.,"  March, 
1905,  p.  390.     Mooers,  "Amer.  Jour,  of  Insanity,"   1904,  No.   i. 


THE    NERVOUS    SYSTEM.  873 

bacilli,  ami  that  therefore  mixed  lesions  occur.  The  larger  masses  press 
upon  and  destroy  tracts,  interfere  with  the  vascular  supply  to  contiguous 
tissues,  ami  may,  in  this  way,  be  associatrd  with  softening. 

Tuberculosis  of  the  Central  Nervous  System.' — Coincident  with  the 
eruption  of  miliary  tubercles  in  the  meninges,  lesions  of  the  same 
character  may  be  produced  in  the  brain-substance;  the  cortical  portions 
are  most  frequently  affected,  though  in  some  instances  the  deeper  parts 
are  also  diseased.  These  miliary  tubercles  are  gray  or  yellowish- white, 
and  are  softened  in  the  center;  hemorrhages  sometimes  occur  around 
them.  Thev  are,  of  course,  surrounded  by  an  area  of  inflammatory 
tissue.  These  softened  areas  may  coalesce,  and  much  larger  tubercles 
result.  However,  the  large  solitary  tubercles  generally  occur  as  a 
result  of  the  fact  that  but  few  tubercles  were  present,  and  the  disease 
consequentlv  ran  a  ver>'  protracted  course,  and  each  lesion  had  sufficient 
time  to  become  large.'  The  large  tuberculomas  (p.  153),  also  called 
conglomerate  tubercles,^  resemble  the  smaller  ones,  but  may  become 
infected  by  pyogenic  organisms,  and  as  a  consequence  their  contents 
sometimes' become  puriform;  they  are  most  common  in  the  cerebellum. 
Microscopically,  the  tubercles  of  the  central  nervous  system  in  everv'  way 
conform  to  similar  bodies  occurring  elsewhere.  Tuberculous  menin- 
gitis mav  occur  independently  of  lesions  in  the  brain  or  cord,  and  is 
sometimes  due  to  direct  extension  from  contiguous  osseous  structures, 
especiallv  in  the  bodies  of  the  vertebrae.  In  a  general  way,  tuberculosis 
of  the  meninges  follows  the  usual  types  of  tuberculosis  of  the  serous 
membranes  (p.  475).  In  some  cases  miliary  infiltration  of  the  pia- 
arachnoid  occurs;  in  other  instances  the  inflammation  produces  a  sero- 
fibrinous exudation;  there  may  be  conspicuous  accumulation  of  fluid 
in  the  interstices  of  the  pia  and  arachnoid  and  accumulation  in  the 
ventricles.  A  definite  tuberculoma,  or  circumscribed  area  of  chronic 
caseous  tuberculosis,  is  occasionallv  seen. 

Multiple  Sclerosis'  (Insular  Sclerosis).— In  this  disease  there  occurs 
throughout  the  entire  central  nervous  system  areas  in  which  the  neuroglia 
is  greatlv  increased  in  amount  and  the  individual  fibers  are  thickened 
and  probablv  elongated.  As  the  neuroglia  corresponds  to  the  fibrous 
tissue  of  other  parts  of  the  body,  its  hyperplastic  condition  in  these 
instances  mav  be  looked  upon  as  analogous  to  the  fibrosis  occurring 
in  the  kidnev,  liver,  and  other  organs.  These  sclerotic  changes  may 
also  be  compared  to  those  tumors  of  the  central  nervous  system  called 
glioniata,  as  in  both  instances  the  tissue  of  which  the  new  formation 
consists  is  hyperplastic  neuroglia;  indeed,  it  can  not  be  said  that  there 
is  any  sharp'  line  of  distinction  between  the  two  conditions — the  two 
bearing  exactlv  the  same  relation  to  each  other  that  newly  formed 
fibrous  tissue  in  organs  bears  to  the  fibromata.     The  process,  which  is  a 

•  Trcvelyan,  "Lancet,"  Nov.  7,  1903,  p.  1276. 

'  Barbacci,  "Centralbl.  f.  allp.  Path.  u.  path.  Anat.."  1902.  p.  833. 

»  Shover  "Jour,  of  Path,  and  Bact,"  March,  1902.  Bielschowsky.  NeurolOK- 
CentralbL."*Aug.  16.  1903.  Strauhuber.  "  ZieKler's  Beitr,"  1003.  B«l.  33.  p.  40Q. 
also  "Xeurolog.  Centralbl."  Jan..  1904.  Bd.  23.  N'o-  3.  Spiller,  "Amer.  Jour,  of 
Med  Sci  "  Jan.,  1903.  Bramwell,  "  Review  of  Neurol,  and  Ps>-ch.,  Jan.,  1903. 
Borst  "  Lubarsch  and  Ostertag's  Ergebnis.se  <lcr  allg.  Path.  u.  path.  Anat  ,  Neun- 
ter  la'hrg  Abt.  I,  1903.  p.  67.  Tredgold,  "Review  of  Neurol,  and  Psych..  July. 
1904.  Sluller.  "Die  Multiple  Sklcrose  d.  Gehims  u.  Rue  ken  marks,"  Jena.  1904. 
Dercum  and  Gordon,  "Amer.  Jour,  of  Med.  Sci."  Feb.    1905.  p.  253. 


874 


SPECIAL    PATHOLOGY. 


Fig.  411. — Disseminated  Sclerosis. — {Gordon.) 
Areas  of  sclerosis  in  the  pyramids  and  nuclei  of  the  medulla 
sclerotic  areas  are  unstained. 


The 


very  chronic  one,  sometimes  follows  such  diseases  as  influenza,  malarial 
and  typhoid  fevers,  but  there  is  no  conclusive  evidence  that  they 
are  the  cause;  the  same  is  true  of  syphihs  and  trauma.  The  sclerotic 
areas  vary  much  in  size,  some  being  only  microscopic  and  others 
involving    an  entire    lobe  of   the  brain;  the  nodules  may   be   scanty 

or  numerous,  often  the 
latter,  and  are  irregu- 
larly distributed  in  both 
brain  and  spinal  cord; 
they  show  no  tendency 
to  follow  tracts.  In 
the  white  substance  the 
areas  of  sclerosis,  when 
sufficiently  large, may  be 
detected  by  their  pinkish 
color,  and  by  being  con- 
siderably harder  than 
the  neighboring  normal 
brain  tissue ;  in  the  gray 
substance  they  are  so 
nearly  the  same  color  as 
the  normal  tissue  that  it 
is  very  difficult  to  distinguish  them.  In  some  cases  the  neuroglia  just 
beneath  the  epithelial  lining  of  the  ventricles  becomes  hyperplastic, 
and  the  resulting  condition  is  called  ependymal  sclerosis.  The  sclerosis 
may  be  diffuse,  giving  rise  to  a  condition  of  uniform  thickening,  or  it  may 
occur  in  many  minute  circumscribed  areas ;  the  former  variety  of  the  dis- 
ease is  called  smooth,  and 

the  latter  granular  epen-  ^,,«««,» 

dymal  sclerosis.     There  ^,„ 

is  a  form  of  sclerotic 
change  known  as  lobar 
sclerosis,  affecting  one  or 
more  lobes  of  the  brain, 
and  sometimes  the  en- 
tire brain.  The  condi- 
tion seems  to  have,  in 
the  beginning,  some  re- 
lation to  the  cerebral 
blood-supply,  as  the 
lesion  nearly  always  cor- 
responds to  the  distribu- 
tion of  some  artery.  The 
entire  region  involved  is 
very  hard,  the  gyri  are 
depressed,  and  the  pia  is 
adherent.  Secondary  degenerations  are  more  pronounced  in  this  form 
than  in  the  other  varieties. 

Microscopically,  the  sclerosed  area  is  composed  of  hypertrophic  or 
hyperplastic  neuroglia  fibers  (demonstrable  by  the  method  of  Mallory, 
see  p.  840),  and  the  neuroglia  cells  are  also  greatly  increased.  The 
nervous  elements  show  more  or  less  evidence  of  degenerative  changes; 


Fig.  412. — Disseminated  Sclerosis. — {Gordon). 

Areas  of  sclerosis  in  pyramidal  tracts,  Gowers'  tract,  and  direct  cerebellar 

tract.     Weigert's  method;  the  sclerotic  areas  are  unstained. 


THE    N'ERVOUS    SYSTEM.  875 

the  myelin  sheatlis  of  the  nerves  are  largely  (ii-stroycd,  but,  strange 
to  say,  the  axis-cylinders  do  not  exhibit,  as  a  rule,  marked  alter- 
ations; they  are,  in  the  majority  of  cases,  preserved,  and  this  in- 
tegrity explains  the  absence  of  secondary  degenerations  in  the  various 
tracts.  It  is  to  be  remembered,  therefore,  that  the  characteristic  histo- 
logic feature  of  multiple  sclerosis  consists  of  proliferation  of  neuroglia  and 
destruction  of  myelin  sheaths  of  nerve-fibers,  without  system  degener- 
ation of  any  tract.  The  morbid  changes  are  more  pronounced  around 
the  small  blood-vessels,  the  walls  of  which  are  usually  thickened  and  fre- 
quently show  more  or  less  hyaline  transformation.  Compound  granule 
cells  (p.  865)  are  often  found  in  the  sclerosed  areas.  Other  bodies,  the 
result  of  degenerative  change,  are  also  frequently  encountered  in  these 
lesions — namely,  the  corpora  a))iylacca.  They  are  rounded  or  oval  struc- 
tures, generally  somewhat  larger  than  nerve-cells,  containing  no  nuclei, 
and  staining  brown  with  iodin,  and  a  dark-blue  color  with  toluidin-blue. 

Tumors  of  the  brain*  may  be  primary  or  secondar}'.  Probably  the 
most  frequent  primary  cerebral  tumor  is  a  new  growth,  peculiar  to  the 
central  nervous  system,  called  glioma.  The  tumor  is  usually  found  in 
the  cortical  portion  of  the  cerebrum,  and,  as  a  rule,  does  not  protrude 
notably  beyond  the  surface.  On  section  it  is  found  to  consist  of  a  gray 
or  grayish-red  substance,  which  often  contains  whitish  spots  and  hem- 
orrhagic foci;  some  parts  of  the  tumor  are  not  uncommonly  of  a  gelatin- 
ous consistency.  Blood  may  be  extravasated  into  the  tumor  to  such 
an  extent  that  it  has  the  appearance  of  a  massive  hemorrhage  into  the 
cerebral  tissue.  It  sometimes  happens  that  the  brain-substance  in  the 
vicinity  of  the  tumor  is  more  or  less  softened  as  a  result  of  the  pressure 
exerted  by  the  neoplasm. 

Microscopically,  these  tumors  consist  of  hyperplastic  neuroglia; 
there  is  an  enormous  increase  in  the  number  of  the  glia  cells,  and  the 
neuroglia  fibers  around  them  are  thicker  than  normal  and  are  far  more 
numerous  than  in  the  normal  brain.  In  the  center  of  the  tumor  neither 
nerve-cells  nor  axis-cylinders  are  found,  but  if  the  growth  gradually 
merges  into  the  contiguous  nervous  substance,  as  it  not  infrequently 
does,  the  edges  of  the  tumor  contain  these  elements,  and  the  margin  of 
the  neoplasm  is  proportionately  diffuse  and  ill-defined.  The  blood- 
vessels are  usually  very  large  and  numerous;  their  walls  often  show 
hyaline  degeneration,  and  the  outer  coats  are  sometimes  thickened. 

If  the  tumor  contains  nerve-cells,  with  or  without  nerve-fibers,  it  is 
called  ganglionic  nenroglioma.  If  such  neoplasms  involve  the  white 
matter  of  the  convolutions  or  the  centrum  ovale,  nerve-cells  are  fre- 

•  Hartmann,  "  Wien.  klin.  Woch.,"  May  22.  1902.  Gill)ert-Ballet  and  Aniiand 
Delille,  "  Nouv.  Iconograph.  de  la  Salp(}triere,"  May  and  June,  IQ02,  pp.  201-222. 
Philipi)e,  Cestan  and  Oberthur,  "Revue  Neuroloj'.,^'  Aur.  31.  1002.  p.  Sio.  Biel- 
schowsky,  "Deut.  Zeit.  f.  Xcrvenheilk.,"  iqo2.  I^d.  xxii.  Sa.xcr.  "Zieg.  Beitr.," 
IQ02,  Bd.  xxxii.  Siefert,  "  Munch,  med.  Woch.,"  .May  20,  1002.  Hollis,  "Lancet," 
March  28,  1903,  p.  884.  Starr,  "Jour.  Nerv.  and  .Mcnt.  Disease,"  July,  1903.  P- 
398.  Blackburn,  monograph  entitled  "A  Study  of  29  Cases  of  Intracranial  Tumor 
found  in  1642  Postmortems  in  Cases  of  Mental  iDisease,"  Washington,  D.  C.  1903. 
Woolsey.  "  Amer.  Jour,  of  Med.  Sci.,"  Dec.,  1903.  p.  956.  Kufs,  "Arch.  f.  Psych, 
u.  NervtMikrank.,"  1904,  Bd.  xxxviii,  Xo.  3.  Stoerk,  "Wien.  klin.  Woch.,"  1904. 
No.  7,  p.  I.S4.  lumucopulo,  "  Arljeit.  a.  d.  N'euro.  Inst.  a.  d.  Wiener  Univ.,"  1904. 
Bd.  xi.  Walker,  "Jour,  of  Path,  and  Bact,"  Nov.,  1004.  p.  81.  Weisenburg. 
"  N.  Y.  Med.  Jour.,"  Feb.  1 1.  loos.  p.  ;Si  :  also.  "  Prf>cecd.  of  Path.  Soc.  of  Phila.," 
Feb.  28,  1905,  p.  102. 


876 


SPECIAL    PATHOLOGY. 


quently  present.     These  tumors  resemble  the  simple  glioma,  and,  with 
the  exception  that  they  contain,  in  addition  to  the  neuroglia,  the  other 

elements  of  normal  nervous 
substance  in  small  quantity, 
they  are  identical.  (See  Gli- 
oma, p.  320.)  Gliomatous 
tumors  appear  to  owe  their 
origin  to  defects  in  develop- 
ment. The  new  growth  may, 
to  a  certain  extent,  present 
the  appearance  of  sarcoma; 
under  these  circumstances 
the  tumor  is  a  mixed  one,  and 
may  be  called  a  gliosarcoma; 
at  present  the  term  gliosar- 
coma is  in  disrepute,  and  I 
believe  deservedly  so;  it  is 
extremely  doubtful  if  the  two 
neoplasms  are  in  any  way  re- 
lated, or  are  ever  concurrent. 
Sarcomata  of  the  brain 
occur  with  less  frequency  than  the  gliomata.  The  tumors  show  the  usual 
tendencv  to  remain,  in  a  measure,  distinct  from  the  normal  structure  of 


Fig.  413. — Sarcoma  of  Brain. 
Mesial  part  of    inferior    frontal    convolution.     (Dr.   Funke's 
case.)     A.  Tumor,  in  the  left  half  of  which  considerable 
hemorrhage  has  occurred. 


B 


Fig.  414. — Sarcoma  of  Brain. 
Mesial  part  of  inferior  frontal  convolution.     (Dr.  Funke's  case.)    A.  Cellular  areas;    mostly  spindle  cells.     B. 
Areas  of  hyaline  fibrous    tissue.     C.  Large  hlood-channel.     There    are    many  smaller  channels,  some  of 
which  have  ruptured,  causing  interstitial  hemorrhage. 


the  part,  though  to  a  varying  degree  they  infiltrate  contiguous  tissues, 
especially  the  membranes.     The  meninges  in  the  vicinity  are  often  in- 


THE    NERVOUS    SYSTEM.  877 

tlanied,  and  the  adjacent  nerve  substance  is  usually  more  or  less  softened. 
Within  the  tumors,  hemorrhages  and  softening  often  occur.  In  certain 
forms  of  cerebral  sarcoma,  parts  of  the  neoplasm  become  calcified,  and 
the  tumor  is  called  a  psamnioma  (p.  359). 

Angiotnata  of  the  brain  sometimes  occur;  the  tumors  are  quite  small, 
but  may  be  multiple.  They  appear  as  small  red  extremely  vascular 
areas  and  are  probably  of  congenital  origin.  Fibromata  are  very  rare 
cerebral  tumors.  Oslconiata,  lipomata,  and  cholcstcomata  arc  occasionally 
seen.  Carcinomata  are  usually  secondary ;  such  masses  possess  the  ar- 
chitecture and  peculiarities  of  the  variety  of  tumors  from  which  they 
originated.  A  not  infrequent  manifestation  of  cancer  results  from 
extension  into  the  spinal  canal  of  secondary  growths  arising  in  the 
bodies  of  the  vertebrae ;  this  condition  is  commonly  a  sequence  of  car- 
cinoma of  the  mammary  gland.  Primary  carcinoma  may,  however, 
occur,  beginning  in  the  epithelial  cells  of  the  ventricles.  Secondar\' 
sarcomata  are  also  sometimes  observed.  Tumors  arising  from  pig- 
mented moles  (p.  357)  frequently  manifest  metastasis  to  the  brain; 
the  growths  are  usually  multiple  (see  Fig.  205,  p.  358).  Both  primary 
and  secondary'  malignant  tumors  of  the  brain  are  commonly  infiltrated 
by  blood  and  may  be  mistaken  for  areas  of  hemorrhage.  This  state- 
rtient  applies  to  most  neoplasms,  but  is  particularly  true  of  chorioepi- 
thelioma  (p.  354).  . 

Cysts  of  the  Brain.' — Dermoid  cysts,  which  are  sometimes  multiple, 
are  occasionallv  observed  in  the  cranial  cavity.  Cystic  dilatation  oj 
the  fourth  ventricle,  due  to  the  occlusion  of  the  orifice  by  which  its  fluids 
are  drained,  sometimes  occurs.  Parasitic  cysts  (cysticcrcus  and  hydatid) 
may  be  situated  in  the  brain  tissue,  or  choroid  plexus,  or  be  free  in  the 
ventricvdar  cavities. 

Tumors,  cysts,  gummata,  tuberculomata,  and  actinomycotic  masses 
give  rise  to  important  structural  alterations  in  the  contiguous  brain 
tissue,  and,  if  occupving  certain  locations,  press  upon  tracts  and  induce 
secondary  degenerations  (p.  860).  Irritation  produced  by  the  mass 
mav  cause  inflammation  of  the  adjacent  brain  tissue  or  meninges. 
Interference  with  the  circulation  sometimes  causes  softening;  pressure 
on  the  aqueduct  of  Sylvius  prevents  escape  of  fluid  from  the  ventricles 
and  gives  rise  to  internal  livdrocejihalus. 

Diseases  of  the  Pituitary  Body.' — Enlargement,  or  tumor  formation 
affecting  this  bodv  has  frequently  been  observed  in  acromegaly  (see 
p.  806);  twentv-five  tumors  of  the  hypophy.sis  without  acromegaly 
are  on  record,  and  numerous  cases  of  the  latter  affection,  in  which  no 
structural  lesion  could  be  demonstrated  in  the  pituitar}\  have  been 
reported.     Tuberculosis  and  gummata  are  occasionally  found   in   the 

'  Diamond  "Tour.  .Amer.  Med.  Assoc.,"  June  17.  1899.  Askanazy.  "Deut. 
med  Woch.,"  June  12.  1902.  ReRfnardo.  "Semana  Medica."  Buenos  A yres. 
iQo?  No  47.  Salvador  and  de  Leon.  Tht^se  de  Pans,  iqoj.  No.  35S.  Marag- 
liano.  -Gaz.  dcKli  Osped.  e.  delle  Clin.."  March.  1904.  vol  xxv.  .\lquier  and 
Courtellemont,  "Revue  Neurol.."  June  30.  1904.  P-  635.  Hunt.  "Amer.  Jotir. 
of  Med.  Sci,"  March.  IQ04.  404-  „  ..„  .      ,     ,    ,  ,. 

'Erdheim.  "Zieg.  Beitr."  1003.  Bd.  3.V  P-  158-  Berper.  Zeitsch.  r  klin. 
Med  "  Bd  liv.  s.  6.  Guerrini.  "Centralbl.  f.  allg.  Path.  u.  path.  Anat..  March 
i;  100^  p  177  '  Zak.  "Wien.  klin.  Rundschau."  Bd.  xvni.  Nos.  9  to  11.  J^oHa- 
rits,  "^eut.  Zeit.  f.  Nervenheilk."  Bd.  xxviii.  No.  i.  Stadclmann.  "Zeit.  f. 
klin.   Med.."   Bd.    >,. 


878 


SPECIAL    PATHOLOGY. 


pituitary  body.  The  organ  is  rarely  the  seat  of.  .tumors.  The  most 
common  of  these  are  adenomata,  which  are  composed  of  hyperplastic 
follicles  of  the  anterior  lobe  of  the  body.  Carcinomata,  sarcomata, 
endothdiomata,  lipomata,  and  tcratomata  have  been  observed. 

Diseases  of  the  Pineal  Gland. — This  body  is  very  rarely  the  seat  of 
primary  disease.  The  most  frequent  alteration  is  an  increase  in  the 
quantity  of  the  calcareous  material  contained  within  it,  and  cystic  de- 
generation is  sometimes  encountered.     Tumors  are  very  rare. 

Diseases  of  the  Larger  Blood-vessels  of  the  Cranium. — The  great  vessels 
at   the   base   of   the    brain   not   infrequently   become    diseased.       The 

most  frequent  change 
observed  is  atheroma. 
(See  p.  520.)  Aneur- 
ysms are  not  common, 
but  are  occasionally  en- 
countered. 


THE  SPINAL  CORD. 

Remarks  on  the 
Functions  of  the  Gray 
and  the  White  Matter 
of  the  Cord. — A  com- 
prehension of  the  dis- 
eases affecting  the 
spinal  cord  is  facili- 
tated by  a  knowledge 
of  the  function  of  the 
different  parts,  and  for 
this  reason  the  follow- 
ing brief  summary  is 
given :  Anatomically 
the  spinal  cord  consists 
of  a  central  mass  of 
gray  matter,  on  trans- 
verse section  shaped 
something  like  the  let- 
ter H,  surrounded  by 
white  substance.  The 
latter  structure  is  uni- 
formly composed  of 
fibers  and  is  therefore  homogeneous ;  a  knowledge  of  the  physiology  of  this 
part  of  the  cord  shows  that  the  white  substance  consists  of  tracts  or  sys- 
tems of  fibers  possessing  different  functions.  The  posterior  columns  {tracts 
of  Goll  and  Bnrdach)  are  sensory  in  function  and  are  physiologically  con- 
nected with  the  posterior  root  and  spinal  ganglia,  from  which  the  major 
part  of  the  fibers  arise.  Sensory  stimuli  coming  from  the  peripheral 
nerves  are  transmitted  through  the  spinal  ganglia  and  posterior  root  to 
the  columns  forming  the  posterior  tracts  of  the  cord.  It  will  therefore 
be  seen  that  a  lesion  of  the  sensory  pathway,  between  the  spinal  ganglia 
and  the  cord,  or  within  the  latter  structure,  severs  the  fibers  from  their 
ganglion  cells  and  gives  rise  to  a  degeneration  of  the  posterior  columns 


Fig.  415. — Endothelioma  of  Pituitary  Body. 

The  growth  has  extended  into  the  right  orbit  and  penetrated  the  orbital 

plate  of  the  frontal  bone  from  below  upward.     (Dr.  Burr's  case.) 


TIIIv    NERVOUS    SYSTliM. 


879 


(ascending  degeneration).  The  jjosterior  columns  conduct  chiefly  the 
stimuli  necessary  to  the  sense  of  touch  and  the  sense  of  coordination  in 
station  and  gait,  and  therefore  a  lesion  of  these  structures  interferes  with 
the  transmission  of  sensory  impulses  and  disturbs  the  necessary  con- 
nection between  certain  forms  of  sensation  and  coordinated  motion. 
The  direct  a>id  crossed  pyramidal  tracts  are  exclusively  motor  in 
function.  As  the  fibers  contained  within  these  areas  originate  in  the 
motor  area  of  the  brain,  a  lesion  affecting  the  latter  or  severing  the 
fibers  emanating  from  it  necessarily  induces  a  descending  degeneration 
of  the  two  tracts  in  the  cord.  Functionally  the  anterolateral  column 
(Gowers'  tract)  conducts  pain  and  temperature  sensations.  The  pos- 
terolateral or  direct  cerebellar  tract  is  directly  connected  with  the  cere- 
bellum and,  functionally,  controls  the  equilibrium  of  the  body.  The 
last  two  tracts  originate  in  the  cells  of  Clarke's  columns,  transmit  im- 
pulses upward,  and  consequently  degeneration  affecting  their  fibers  is  of 
the  ascending  type. 

Gray  Matter  of  the  Cord. — The  anterior  cornua  consist  chiefly  of  mul- 
tipolar cells  (p.  835)  the  axis- 
cylinders  of  which  form  at 
their  exit  from  the  cord  the 
anterior  roots;  the  latter  are 
continuous  with  the  motor 
fibers  of  the  nerve-trunks  to 
the  periphery  of  the  body. 
Consequently  a  destructive 
lesion  of  the  anterior  cornua 
will  be  followed  by  motor 
symptoms  —  paralysis.  On 
the  other  hand,  it  is  well 
known  that  when  the  an- 
terior cornua  are  diseased, 
trophic  disturbances,  especi- 
ally in  the  muscles,  constantly 
follow.  Therefore  the  ante- 
rior cornua  have  a  double  function — motor  and  trophic.  As  to  the  pos- 
terior cornua,  an  isolated  lesion  of  their  cells  is  rare.  The  function  of  the 
cells  of  Clarke's  columns  is  mentioned  above. 

Circulatory  Disturbances. — Active  hyperemia  of  the  cord  probably 
occurs  only  in  the  beginning  of  infiammation;  it  is  certain  that  we  know 
nothing  of  hyperemia  from  other  causes.  Passive  hyperemia  may  result 
from  the  recumbent  posture  if  the  individual  be  very  weak.  The  cord 
would  probably  appear,  under  those  circumstances,  of  a  darker  color  than 
normal. 

.4  nemia  of  the  cord  occurs  under  the  same  circumstances  that  give  rise 
to  a  like  condition  of  the  brain;  exhausting  hemorrhages,  chlorosis, 
pernicious  anemia,  leukemia,  and  all  of  those  diseases  accompanied  by 
lessened  richness  of  the  blood  may  cause  the  condition.  The  affected 
cord  is  paler  than  normal  on  removal,  but  the  warning  given  in  connec- 
tion with  hyperemia  and  anemia  of  the  l)rain  (see  p.  857)  applies  with 
equal  force  here.  The  changes  in  the  spinal  cord  accompanying  per- 
nicious anemia '  consist  of  a  diffuse  degeneration  aflfecting  all  the  tracts 

'Billings,  "Chicago  Mod.  Recorder,"  Jan.,  190^.  p.  i.  Taylor  "Brain." 
Spring.    1904.  p.   27. 


Fio.  416. — Secondary   DECENtRATioN  or   Posterior  Col- 
umns DOE  TO  Primary  Lesion  in  the  Posterior  R(X)ts. 
— {Gordon.) 
The  degenerated  parts  (sclerotic  areas)  arc  unstained. 


88o 


SPECIAL    PATHOLOGY. 


and  a  more  marked  degenerative  change  the  conspicuous  lesions  of  which 
are  situated  in  the  posterior  and  lateral  columns ;  the  alteration  resembles 
combined  sclerosis,  but  lacks  uniformity  in  distribution.  The  gray 
matter  as  well  as  the  spinal  ganglia  are  notably  not  affected. 

Hemorrhages  into  the  cord  are  usually  the  result  of  rupture  of  a  blood- 
vessel from  injury;  this  is  especially  the  case  if  the  hemorrhage  be 
at  all  large.  Minute  hemorrhages  sometimes  occur  into  the  substance 
of  the  spinal  cord  during  acute  disease;  the  blood  may  be  extra vasated 
into  the  central  canal  of  the  cord.  The  condition  is  called  hemato- 
myelia.^  The  extra  vasated  blood  causes  dissociation  and  disintegration 
of  the  nerve-fibers  and  cells  of  the  affected  area;  an  inflammatory 
reaction  occurs  in  the  contiguous  tissues,  which  are  infiltrated  with 
mononuclear  leukocytes  and  contain  numerous  granule   cells.      If  the 


,  .^i^^^^-i0^ii^ 


:~       "^^^^ 


J^. 


\<$^% 


iQy 


Fig.  417. — Spinal  Cord. 
Areas  of  sclerosis  due  to  pernicious  anemia.     The  sclerotic  parts  are  unstained.     Weigert's  method. 

patient  survive,  the  blood  may  be  absorbed;  a  cyst  sometimes  forms,  and 
the  glia  at  the  margin  of  the  lesion  proliferates.  As  a  result  of  the 
destruction  of  fibers  secondar}^  degenerative  changes  develop. 

Myelitis  or  inflammation  of  the  cord"  may  be  acute,  subactUe,  or  chronic, 
depending  on  the  cause.  The  acute  and  subacute  forms  occasionally  be- 
come chronic.  There  are  several  varieties  of  myelitis  that  show  sufficiently 
distinctive  features  to  merit  separate  description,  but  the  form  meant 
when  the  term  myelitis  is  used  without  qualification  will  be  first  con- 
sidered. 

Laignel- 
Collins 


'Bruce,    "Scottish   Med.    and    Surg,    Jour.,"    Aug.,    1902,   p.    107. 
Lavastine,  "Nouv.  Iconograph.  de  la  Salpetriere,"  May  and  June,  1904. 
and  Zabriskie,  "Med.  Record,"  Sept.  3,  1904,  p.  361. 

^  Erb,  "Brit.  Med.  Jour.,"  Oct.  11,  1902,  p.  1114.  Singer,  "Brain, 
Part  II,  332.  Stewart,  "Trans.  Path.  Soc.  of  London,"  1902,  vol.  53,  p.  i. 
and  Gallavardin,  "Revue  Neurolog.,"  Oct.,  1903,  p.  999.  Collier,  " 
Spring,  1904.  Ghilarducci,  "II  Policlinico, "  Rome,  1904,  No.  25. 
"Jour,  of  Nerv.  and  Ment.  Dis.,"  Nov.,  1904,  p.  695.  Baudron,  "Annals 
Chirurg.  du  Centro,"  Nov.  21,  1904.  Rhein,  "Univ.  of  Penna.  Med.  Bull. 
1905.  P-  373- 


1902, 
Weill 
Brain," 
Collins, 
Medic  o- 
,"  Jan., 


TIIK    NKKVOUS    SYSTKM. 


88l 


Perhaps  the  most  freciucnt  cause  of  nnelitis  is  injury  to  the  cord. 
riosely  rehited  to  this  are  those  inllanmiatious,  always  more  or  less 
(.hronic,  that  are  the  result  of  the  long-continued  pressure  of  tumors, 
aneurysms,  and  cysts,  ami  of  the  compression  exerted  by  deformed 
vertebrcC  in  caries  of  these  bones. 

Myelitis,  secondary  to  intlammations  of  the  pia-arachnoid,  often 
occurs;  it  is,  therefore,  present  in  cerebrospinal  meninj^itis,  tuberculous 
meninijitis,  and  other  infective  lesions  of  these  membranes.  In  such 
conditions  as  pyemia,  septicemia,  and  other  diseases  in  which  bacteria 
are  present  in  the  blood  myelitis  is  occasionally  observed;  it  is  usually 
of  a  suppurative  character,  and  is  accom])anie(l  by  a  similar  process  in 
the  cerebral  tissues.  To  this  class  pr()])ably  boloni,^  those  inflammations 
of  the  cord  that  follow 
smallpox,  rheumatism, 
typhoid  fever,  and  typhus 
fever.  Sexual  excesses, 
the  suppression  of  the 
menses,  and  cold  are  sup- 
posed sometimes  to  occa- 
sion the  disease;  at  most 
they  are  nothintj  more 
than  predisposing  factors. 
Acute  myelitis  is  probabh' 
alwavs  infective,  toxemic, 
traumatic,  or  embolic. 
Syphilis  is  a  frequent 
cause  of  the  ciironic 
form. 

Morbid  Aiiatotiy. — 
Both  the  white  and  gray 
matter  may  be  affected. 
If  the  white  substance  be 
alone  attacked,  the  dis- 
ease is   called   leukomye- 

litis  ;  if  the  intlainmation  be  confined  to  the  gray  matter,  the  condition  is 
termed  poliomyelitis.  The  entire  thickness  of  the  cord  may  be  diseased, 
in  which  case  the  affection  is  called  transverse  myelitis.  If  an  extensive 
area  be  involved,  the  myelitis  is  said  to  l)c  </////(>< .  if  a  small  area  alone 
of  the  cord  be  the  seat  of  the  disease,  the  condition  is  termed  focal 
))ivelitis;  when  many  foci  of  inflammation  are  present,  the  condition  is 
known  as  disscininatai  myelitis.  Inflammation  just  around  the  central 
canal  and  extending  more  or  less  into  the  surrounding  gray  substance  is 
called  central  myelitis;  the  anterior  cornua  may  be  also  affected  without 
disease  in  other  parts  of  the  gray  matter — anterior  poliomyelitis. 

On  examination,  the  meninges  in  the  vicinity  of  the  diseased  area 
are  found  to  exhibit  more  or  less  evidence  of  inflammation.  The  cord 
is  usuallv  swollen  and  softened,  and  on  section  presents  a  reddish 
appearance.  If  the  inflammation  be  intense,  the  substance  of  the 
cord  is  almost  creamy  in  consistence;  and  if  the  amount  of  blood 
extra vasated  into  it  be  consideral)le,  the  di.seascd  area  is  said  to  be  in 
a  state  of  r.-.l  ^nttniin''  .\t  :i  later  iicriotl  the  iiiL'ment  contained  in 
57 


41S. — Myelitis.    .Akjias  « 
TO  Tuberculosis 


S<lf-rK.NlNC.    IN    THE     CuRD    iJUE 

y  THE  Vertebr  ♦;. 


882  SPECIAL    PATHOLOGY. 

the  effused  blood  undergoes  changes,  converting  the  softened  tissues 
into  a  vellow,  and  finally  a  white  substance,  and  the  last  two  conditions 
are  therefore  called  yclloic  and  white  softening  respective^.  If  the 
disease  be  subacute  or  chronic,  the  cord  may  iDe  either  of  a  normal, 
increased,  or  diminished  consistence;  it  usually  presents  a  grayish  ap- 
pearance, as  a  result  of  proliferation  of  the  neuroglia;  late  in  the  disease 
small  cavities  in  the  affected  area  are  occasionally  encountered. 

Microscopically,  the  blood-vessels  are  found  to  be  greatly  dilated  in 
the  acute  forms,  and  there  is  often  considerable  blood  extra vasated  into 
the  affected  tissues.  The  myelin  sheaths  of  the  nerves  swell  and  become 
nodose,  exhibiting  here  and  there  small  areas  of  fatty  degeneration; 
the  axis-cylindefs  are  swollen  and  granular,  and  finally  disintegrate. 
The  nerve-cells  at  first  manifest  tigrolysis,  chromatolysis,  and  plasmolysis, 
in  the  order  named,  and  later  are  necrotic  or  fatty;  they  are  vacuolated, 
the  chromophilic  substance  no  longer  stains,  and,  finally,  disintegration 
occurs.  The  glia  cells  in  acute  cases  undergo  but  little  change,  though 
they  are  usually  somewhat  swollen  and  increased  in  number.  As  the 
process  grows  older,  and  if  it  be  pronounced,  there  remains  of  the  original 
nerve  elements  scarcely  more  than  a  few  fragments ;  compound  granule 
cells  (phagocytes)  may  appear  in  considerable  numbers.  If  the  diseased 
tissues  contain  blood,  many  cells,  called  pigment  granule  cells,  may  be 
seen  containing  the  pigments  of  the  disintegrating  blood.  At  a  later 
period  the  granular  detritus  resulting  from  destruction  of  the  nervous 
elements  disappears,  connective-tissue  cells  make  their  appearance, 
more  or  less  fibrosis  occurs,  and  the  neuroglia  fibers  greatly  increase. 
Corpora  amylacea  often  form  in  the  tissues  as  the  process  becomes 
old. 

Secondary  degenerations  (p.  860)  of  the  columns  of  the  cord  commonly 
follow  myelitis;  the  nature  and  extent  of  these  depend  on  the  situation 
and  size  of  the  primary  lesion  in  the  cord.  From  the  initial  focus,  what- 
ever its  character,  the  degeneration  proceeds  along  the  nerve-fibers  in 
the  same  direction  in  which  impulses  were  carried  before  the  injury 
occurred;  this  depends  upon  the  fact  that  the  axis-cylinders,  being 
essentially  a  part  of  the  nerve-cells  from  which  they  take  their  origin,  are 
no  longer  properh'  nourished  after  separation  from  the  body  of  the  cells. 
Lesions  of  the  cord,  therefore,  cause  descending  degeneration  in  motor 
fibers  and  ascending  degeneration  in  the  sensory  columns.  As  myelitis 
may  affect  any  of  these  structures  it  is  possible  to  have  alterations 
resembling  those  observed  in  the  true  system  diseases;  thus,  if  the 
posterior  columns  are  involved,  the  alterations  resemble  tabes.  If  the 
lateral  columns  are  affected,  the  form  is  that  of  primary  lateral  sclerosis, 
and  when  both  lateral  and  posterior  tracts  are  attacked,  the  lesion 
assumes  the  characters  of  a  combined  sclerosis.  These  varieties  are 
observed  only  in  the  chronic  cases  of  myelitis  after  the  secondary 
degenerations  are  definitely  established. 

Acute  ascending  paralysis^  (Landry)  is  a  name  applied  to  a  clinical 
syndrome  the  anatomic  basis  of  which  is  probably  not  always  the  same. 

'  Sherman  and  Spiller,  "  Phila.  Med.  Jour.,"  March  31,  1900.  Diller,  "Jour. 
of  Nerv.  and  Ment.  Dis.,"  Oct.,  1902,  p.  577.  Roll3^  "Miinch.  med.  Woch.," 
July  28,  1903,  p.  1283.  Preobragenky,  "Arch,  de  Neurol.,"  1904,  xviii,  p.  87. 
Gordinier,  "Albany  Med.  Annals,"  Jan.,  1904.  Hey,  "Miinch.  med.  Woch.," 
Dec.  20,  1904. 


THE    NERVOUS    SYSTEM.  883 

In  many  cases  tlic  clinical  history  and  anatomic  findin^^s  indicate  that 
it  is  a  form  of  neuritis  and  should  be  considered  with  inflammations  of 
nerves.  In  such  instances  no  conspicuous  alterations  are  found  in  the 
spinal  cord.  In  other  cases  inflammatory  lesions  have  been  observed 
in  the  anterior  cornua  justifying  the  name  acute  ascending  poliomyelitis. 
In  some  of  the  reported  cases  the  motor  nuclei  ot  tlu'  tuaiii  wvrr  also 
affected  {iicnlc  poliocuci'phalomyclilis).  1  shall  refer  only  to  the  changes 
that  are  present  in  the  cord  in  cases  in  which  the  anterior  horns  have 
been  found  afTected.  All  observers  are  agree<l  that  it  is  the  result  of 
intense  toxemia  or  is  due  to  infection.  Gordinier  states  that  the  follow- 
ing organisms  have  been  isolated  from  the  lesion:  Streptococci,  staphy- 
lococci, typhoid  bacilli,  the  anthrax  bacillus,  and  a  number  of  unidenti- 
fied bacteria.  It  may,  therefore,  be  assumed  that  the  disease  is  often, 
if  not  always,  a  manifestation  of  infection. 

Morbid  A)taio))iy. — The  cord  frc(iuently  shows  no  gross  evidence  of 
disease;  in  other  cases  some  redness  of  the  gray  matter  and  occasional 
hemorrhagic  areas  in  its  substance  have  been  observed.  Microscopically, 
the  grav  matter  of  the  cord,  medulla,  pons,  cerebrum,  and  cerebellum 
exhibit  the  usual  changes  of  beginning  inflammation :  The  vessels  are  dis- 
tended with  blood,  and  around  many  of  the  smaller  veins  and  the  capil- 
laries collections  of  lymphoid  cells  are  usually  present;  the  nerve-cells 
manifest  the  alterations  usual  in  inflammation;  the  white  matter  is 
sometimes  slightly,  but  evidently  only  secondarily.  afTected.  Inflamma- 
tory' changes  have  been  observed  in  the  nerve-roots  and  peripheral  nerves. 

Acute  poliomyelitis'  is  thought  to  be  due  to  the  same  general  causes 
that  are  believed  to  give  rise  to  the  ordinary  forms  of  inflammation  of  the 
cord,  but  there  are  facts  concerning  it  indicating  that  it  is  a  distinct 
disease — the  result  of  some  morbific  agency  having  a  predilection  for 
this  particular  part  of  the  nervous  system.  Among  such  facts  may  be 
mentioned  that  the  disease  frequently  occurs  without  any  apparent 
cause,  that  it  affects  children  almost  exclusively — the  period  of  life  at 
which  it  comes  on  being  usually  about  that  of  the  first  dentition — is 
occasionally  epidemic,  and  possesses  fairly  constant  anatomic  changes. 
In  support  of  the  view  that  it  is  due  to  a  specific  disease-producing 
factor  is  the  recent  discover^'  of  the  Diplococcus  intracellularis  menin- 
gitidis in  the  tissues  of  the  cord  during  the  acute  stages  of  the  aft'ection. 
An  organism  resembling  the  pneumococcus  has  l)een  identified  in  some 
cases,  and  in  other  instances  no  bacteria  could  be  found.  In  the  epi- 
demic observed  in  Vermont  adults  were  sometimes  attacked  and  oc- 
casionallv  domestic  animals  were  afTected.  Batten  has  recently  urged 
that  the  cord  lesion  depends  upon  embolism  or  thrombosis  of  the  an- 
terior median  vessel  of  the  cord,  and  that  it  may  l)e  produced  by  a  number 
of  organisms. 

Morbid  Atiatomy. — If  the  disease  be  \eT\-  severe,  the  meninges  in  the 
vicinitv  mav  be  slightly  reddened.  On  section  the  gray  matter  in  one 
or  both  of  the  anterior  cornua  is  redder  than  usual,  and.  if  the  ilisease 

'Bury.  "Brit.  Med.  Jour.."  May  24.  kjoj.  .MacKt-nzic,  Med.  Record.  ' 
Oct.  4.  1902.  p.  528.  Batten,  "Lancet."  Dec.  20.  1002.  p.  1O77.  also  "Brain." 
Autumn,  1004,  p.  376.  Pratorius.  "  Inaug.  Diss  "  Munchen.  July,  igo.^.  No.  93. 
Aovama.  "Deut.  Zeit.  f.  Nervenheilk.."  1904.  Bd.  20,  H.  6  and"  7.  Cornell.  "Bull. 
Johns  Hopkins  Hospital,"  Jan..  1905.  p.  11.  Falkner,  "Australasian  Med.  Gaz- 
ette," Oct.  30,  1004.     Still.  "Practitioner,"  Feb..  1905.  ]>.  217. 


884  SPECIAL    PATHOLOGY. 

be  of  a  severe  type  and  somewhat  advanced,  the  tissues  in  this  situation 
are  considerably  softer  than  usual.  After  the  acute  stages  have  passed 
the  affected  area  is  somewhat  more  dense  than  normal,  and  commonly 
shrunken.  Microscopically,  in  the  acute  stage  the  ganglion  cells  present 
the  usual  changes  under  such  circumstances — namely,  they  swell,  the 
chromophilic  substance  undergoes  a  granular  change  or  the  masses  run 
together,  the  nuclei  become  eccentric,  and  the  cells  ultimately  disinte- 
grate. The  axis -cylinders  passing  from  such  nerve-cells  degenerate 
throughout  their  entire  extent,  as  do  also  their  myelin  sheaths.  As  a 
consequence,  the  muscle-fibers  to  which  they  are  supplied  undergo  fatty 
changes,  and  to  a  great  extent  atrophy  and  disappear.  This  change 
in  the  muscles  is  the  most  striking  clinical  phenomenon,  and  as  the  dis- 
ease generally  occurs  in  infants,  it  has  been  long  known  as  infantile 
paralysis.  The  glia  cells  swell  and  proliferate,  and  the  tissues  are  in- 
filtrated to  a  certain  extent  by  small  mononuclear  cells.  The  blood- 
vessels that  penetrate  the  affected  region  are  distended;  their  walls  not 
infrequently  rupture,  and  more  or  less  blood  is  consequently  infiltrated 
into  the  part.  If  the  inflammatory  phenomena  be  severe,  and  if  they 
persist  for  some  time,  the  central  area  of  the  diseased  region  contains 
only  the  granular  debris  resulting  from  degeneration  of  all  of  the 
elements  that  are  present  in  its  formation. 

After  the  acute  stages  have  passed  the  neuroglia  proliferates  and 
gradually  replaces  the  degenerated  tissue.  An  interesting  fact  connected 
with  this  disease  is  that  the  motor  cortex  of  the  brain,  in  connection 
with  the  diseased  parts,  appears  in  the  course  of  time  to  undergo  more 
or  less  atrophy;  this  is  probably  the  result  of  disuse. 

Chronic  Anterior  Poliomyelitis^  {Progressive  Muscular  Atrophy  of 
Spinal  Origin). — Closely  related  to  acute  anterior  poliomyelitis  in  the 
seat  of  its  spinal  lesions  is  the  disease  known  as  progressive  spinal 
muscular  atrophy.  It  is  not,  however,  at  all  certain  whether  the  changes 
in  the  gray  matter  of  the  cord  are  to  be  regarded  as  of  an  inflammator}'' 
or  of  a  degenerative  kind,  and  it  would  therefore  be  obviously  incorrect 
at  the  present  time  to  class  them  with  the  inflammations ;  notwithstand- 
ing the  uncertainty  that  still  exists  respecting  its  character,  the  disease 
is  called  chronic  anterior  poliomyelitis.  In  this  connection  attention 
should  be  directed  to  the  fact  that  injury,  overwork,  exposure  to  cold,  or 
an  attack  of  any  of  the  infectious  diseases  are  regarded  as  the  most 
frequent  causes  of  the  affection;  as  these  are  precisely  the  etiologic 
factors  generally  looked  upon  as  being  most  potent  in  the  production  of 
ordinary  myelitis,  and  as  the  lesion  of  progressive  muscular  atrophy 
could  be  very  well  the  result  of  an  inflammatory  condition,  it  certainly 
requires  no  very  great  stretch  of  the  imagination  to  conceive  a  closer 
relation  between  the  two  than  is  generally  supposed. 

Morbid  Anatomy. — The  gross  changes  in  the  cord  are  never  very 
intense;  hyperemia  is  absent;  in  marked  cases  the  anterior  cornu  may 
be  manifestly  smaller  than  normal.  Histologically,  the  conspicuous 
changes  involve  the  motor  cells  of  the  anterior  cornua.  Mott  states 
that  of  the  three  groups  of  cells,  occupying  the  anterior  horn,  the  outer 
and  middle  disappear;  those  of  the  inner  group  are  less  involved.  Nor- 
mal and  wasting  cells  sometimes  lie  side  by  side.     The  ganglion  cells  in 

'Mott,  "Practitioner,"  May,  1904,  p.  639.  Herbert,  Morley,  Fletcher  and 
Batten,   "Brain,"    1903,   Part   IV,   p.   473. 


THE    NKRVOL'S    SYSTEM.  885 

process  of  disappearing  are  the  seat  of  tigrolysis,  chromatolysis,  and  plas- 
molysis.  Later  ])igmcntation  appears  witliin  the  cell,  and  finally  small 
granules  occujiy  the  spaces  previously  filled  by  the  cells.  As  the  ganglion 
cells  waste  the  neuroglia  j^roliferates.  The  condition  is  believed  to  be 
a  primary  decay  of  the  neurones.  The  alterations  in  the  muscles  are 
those  of  a  progressive  atrophy  (p.  7<S8).  The  nerve-trunks  to  the  affected 
areas  contain  abtnit  half  the  normal  number  of  fibers,  and  these  are 
sensory. 

Amyotrophic  lateral  sclerosis '  is  characterized  by  destruction  of 
the  anterior  cornua  and  sclerosis  of  the  motor  tracts;  it  is,  therefore,  a 
chronic  anterior  poliomyelitis  with  degeneration  of  the  pyramidal 
columns.  In  advanced  cases,  of  long  duration,  changes  have  been 
observed  in  the  medulla,  pons,  crura,  internal  capsule,  and  even  in  the 
cells  of  the  motor  area  in  the  cortex.  The  first  manifestations  of  the 
disease  are  usually  observed  in  the  cervical  cord,  although  it. may  begin 
in  the  medulla.  In  some  cases  the  onset  is  in  the  anterior  cornua,  in 
others  the  pyramidal  tract  appears  to  be  first  involved;  the  disease  is 
essentially  progressive.  It  will  be  observed  that  in  chronic  anterior 
poliomyelitis  the  lower  segment  of  the  motor  neurone  alone  is  involved, 
while  in  amyotrophic  lateral  sclerosis,  both  upper  and  lower  segments 
participate  in  the  degenerative  and  sclerotic  process. 

Progressive  Bulbar  Paralysis  {GlossolabiolaryugcaL  Paralysis). — Very 
closely  related  to  ]jr<)gressive  muscular  atrophy  is  a  disease  of  the 
medulla  known  as  progressive  bulbar  paralysis.  It  attends  conditions 
similar  to  those  accompanying  progressive  spinal  muscular  atrophy, 
and  even  passes  into  it  by  gradual  stages,  or  vice  versa.  In  fact, 
the  only  difference  between  the  two  seems  to  be  the  mere  accident 
of  location,  one  affecting  principally  the  cervical  region  of  the  spine,  and 
the  other  the  medulla,  which  is  but  the  cord  continued  into  the  skull. 
With  the  exception  of  the  difTerence  in  location,  the  two  affections  have 
exactly  the  same  gross  and  microscopic  anatomy.  The  disease  is 
characterized  by  a  primary  and  systematic  lesion  of  the  nuclei  of  the 
cranial  motor  nerves  located  in  the  lower  half  of  the  medulla,  namely, 
of  the  seventh,  ninth,  tenth,  eleventh,  and  twelfth  nerves.  According 
to  Charcot,  the  lesion  of  the  nucleus  of  the  hypoglossus  is  the  most 
pronounced.  The  changes  in  the  cells  of  the  affected  nuclei  are  identical 
with  those  occurring  in  the  ganglion  cells  of  the  cord  in  anterior  polio- 
myelitis. The  roots  of  the  nerves  which  emerge  from  the  nuclei  undergo 
atrophy  and  sclerosis.  The  muscles  supplied  by  diseased  nerves  also 
undergo  atrophic  changes,  which  consist  of  fatty  degeneration  and 
disappearance  of  muscle  substance,  proliferation  of  the  nuclei  of  the 
sarcolemma,  and  increase  of  adipose  and  fibrous  connective  tissues. 
These  changes  are  foun<l  in  the  muscles  of  the  lips,  tongue,  phar\'nx, 
and  larynx. 

Insular  Scleroses  of  the  Cord. — In  discussing  insular  sclerosis  of  the 
brain  (p.  873;  mention  was  made  of  the  fact  that  here  and  there  small 
areas  in  the  cord  were  also  afTected,  and  it  will,  therefore,  not  be  neces- 
sary again  to  refer  to  a  spinal  form  of  the  affection. 

'  Mott,  "Practitioner,"  May,  1904,  p.  639.  Dercum  and  Spillcr.  "Trans,  of 
the  Amer.  Neurolog.  Assoc.,"  1898.  Spiller,  "Univ.  of  Penna.  .Med.  Bull.,"  Jan., 
1905,  p.  390.     Collins,  "Amer.  Jour,  of  Med.  Sci.."  June,  1903. 


886  SPECIAL    PATHOLOGY. 

Tabes/  also  called  posterior  spinal  sclerosis  and  locomotor  ataxia,  is 
the  most  common  and  typical  of  the  system  diseases  affecting  the  cord. 
The  process  is  clearly  traceable  to  syphilis  in  from  eighty  per  cent,  to 
ninety  per  cent,  of  the  patients;  it  is  also  possible  that  alcoholic  ex- 
cesses, exposure  to  cold,  over-exertion,  and  injury  are  responsible  for  a 
small  percentage  of  the  cases.  Exactly  how  the  syphilitic  poison  in- 
duces the  change  has  not  been  definitely  determined.  The  theory  that 
the  lesion  was  primary  in  the  ganglia  of  the  posterior  roots  has  not  been 
supported  by  the  results  of  extended  inquiry.  It  has  been  supposed 
that  the  posterior  roots  are  involved  in  a  meningeal  inflammation  acting 


':'k 


-  ^'  . 

4'  ;' 

t' 

Fig.  4ig. — Spinal  Cord,  Showing  Posterior  Sclerosis. 
Tissue  was  hardened  in  Miillcr's  solution;  sections  stained  in  alkaline  toluidin-blue.     a,  a.  Normal  nerve-fibers. 

b.  Sclerotic  area. 

between  the  ganglia  and  the  point  where    the    fibers  enter   the   cord, 
probably  in  the  arachnoid. 

Morbid  Anatomy. — On  removal  the  cord  generally  presents,  in 
advanced  cases,  a  striking  diminution  in  its  anteroposterior  diameter, 
owing  to  the  fact  that  the  sclerosed  tissue  that  has  taken  the  place  of  the 
nerve-fibers  occupies  less  space  than  the  normal  nerve  substance.     The 

1  Marie  and  Guillain,  "Revue  Neurolog.,"  Jan.  31,  1903,  p.  49,  also  discussion 
p.  103.  Mott,  "Arch,  of  Neurology  of  London  County  Asylum,"  1903.  Collins, 
"Med.  News,"  Jan.  3,  1903,  and  June  13  and  20,  1903';  als'o  "Jour  of  Nerv.  and 
Ment.  Dis.,"  June,  1903.  Weigert,  "  Neurolog.  Centralbl.,"  Aug.  16,  1904,  p. 
738.  Erb,  "Berl.  klin.  Woch.,"  1904,  Nos.  i  to  4.  Hassin,  "Med.  Record," 
Jan.  30,  1904,  p.  16S.  Mobius,  "Jahr.  der  in.  und  ausland.  Gesem.  Med.," 
Jahrgang,  1904,  Heft  i.     Gowers,  "Brit.  Med.  Jour.,"  Jan.  7.  1905. 


TIIH    NKUVOUS    SYSTKM.  887 

newlv  formed  tissue  is  also  of  a  darker  color  than  the  neighborinj;  normal 
l)arts,  and  on  section  its  consistence  is  found  to  be  increased.  The 
disease,  as  a  rule,  first  appears  in  the  lumbar  rej^ion,  and  is  most  intense 
in  this  situation;  however,  in  severe  cases  the  entire  posterior  columns 
of  the  cord  may  be  involved.  The  posterior  nerve-roots  may  also  show 
marked  sclerotic  chani,'e. 

Microscopic  examination  shows  that  the  fibers  of  the  posterior 
column  have  almost  entirely  disappeared,  and  in  their  place  is  a  dense 
network  of  neuroglia  tissue.  In  the  early  stages  fatty  particles  may  be 
seen  occupying  the  places  of  the  nerves.  In  the  later  stages  corpora 
amvlacea  are  numerous.  In  the  upper  portion  of  the  cord  the  substance 
of  the  entire  posterior  columns  is  not  affected,  the  disease  here  being 
limited  to  the  posterior  median  tracts — column  of  Goll.  Even  in  the 
lower  parts  of  the  cord  some  of  the  fibers  always  escape;  a  small  band 
iust  beneath  the  pia,  and  on  each  side  of  the  posterior  part  of  the  pos- 
terior median  septum,  is  usually  intact,  as  are  also  some  fibers  in  the 
anterior  part  of  the  posterolateral  column.  If  the  disease  be  severe 
and  of  long  standing,  more  or  less  sclerosis  may  be  observed  throughout 
the  entire  cord.  f"or  a  more  detailed  description  of  the  minute  changes 
in  the  sclerosis  of  the  nerve  tissues  occurring  in  this  disease  the  reader  is 
referred  to  the  article  on  Insular  Sclerosis  of  the  Brain,  page  873.  The 
grav  matter  is  not  greatly  affected  in  posterior  spinal  sclerosis,  but 
degenerative  changes  occur  in  the  ganglion  cells  of  the  posterior  cornua 
and  in  the  nerve-fibers  of  the  gray  matter,  especially  those  surrounding  the 
vesicular  columns  of  Clarke.  The  nerve-cells  in  the  spinal  root  ganglia 
as  well  as  the  posterior  roots  also  degenerate;  in  some  cases,  usually 
advanced,  the  sensory  nerves  of  the  peripher\-  show  similar  alterations. 

From  what  has  been  said  it  will  be  seen  that  the  disease  does  not 
affect  the  motor  nerves,  and,  although  incoordination  in  movement  is  a 
svmptom  of  the  malady,  the  muscles  are  not  the  seat  of  important 
alterations.  Arthropathies  (p.  830)  also  occur.  The  incoordination  is 
entirely  the  result  of  a  failure  of  the  sensor>-  nerve  to  convey  the  usual 
impulses  to  the  sensorium,  and  a  consequent  vacillation  on  the  part  of 
the  nerve-center,  from  a  lack  of  knowledge  as  to  the  relation  of  the  body 
to  surrounding  objects.     vSee  remarks  on  physiology  of  the  cord.  p.  878. 

Hereditary  Ataxia'  (Friedreich's  Ataxia). — As  this  affection  is  of  a 
heredilarv  nature,  it  seems  liiglily  jiroliaMe  that  its  cause  lies  in  some 
error  of  development. 

Morbid  Auaiomy. — In  this  disease  sclerosis  of  the  posterior  columns 
is  invariably  present,  and,  in  the  main,  the  lesion  is  similar  to  that  of  the 
ordinary  form  of  posterior  spinal  sclerosis.  The  posterior  nerve-roots 
are  also  affected.  In  addition  to  the  sclerosis  of  the  posterior  columns, 
marked  sclerotic  changes  in  the  lateral  motor  and  anterior  columns 
occur;  the  resulting  involvement  of  the  pyramidal  tracts  causes  atrophy 
of  the  muscles  that  are  innervated  by  the  diseased  nerves.  The  micro- 
scopic changes  are  the  same  as  in  the  other  scleroses. 

Primary  lateral  sclerosis  (primary  spastic  paraplegia)  is  characterized 
bv  a  sclerosi.s  of  the  pyramidal  tracts,  huth  lateral  and  anterior,  but 
chiefly  lateral.     The   cord   presents  the  macroscopic  and  microscopic 

'  Gowers.  "Lancet."  April  12.  iqo2.  AuU'rtia  "Arch.  Gen.  de  M<Jd.."  IQ04, 
p.  1002.     Pic  and  Bonnamour.  "Nouv.  iconogr.  de  la  SalpAtri^re."  1904.  No.  2, 

p.  127. 


888  SPECIAL    PATHOLOGY. 

appearances  characteristic  of  all  the  sclerotic  conditions,  and  as  these 
peculiarities  have  been  described  in  connection  with  the  other  forms 
of  sclerosis,  it  would  be  useless  to  repeat  them  here.  The  degenera- 
tion seems  to  be  primary  and  limited  to  the  motor  tract.  In  pure  cases 
the  association  tracts  of  the  cord  are  not  involved  and  the  anterior 
cornua  are  not  diseased. 

Combined  lateral  and  posterior  sclerosis'  (ataxic  paraplegia)  is  a 
disease  closely  related  to  lateral  sclerosis,  and  both  affections  seem  to 
be  produced  by  the  same  causes. 

Morbid  Anatomy. — The  cord  presents  the  combined  lesions  of  pos- 
terior and  lateral  scleroses.  The  lesion  of  the  posterior  columns,  how- 
ever, is  not  identical  with  that  found  in  the  ordinary  posterior 
spinal  sclerosis,  differing  principally  in  the  fact  that  the  disease  is  not 
usually  so  intense,  and  that  the  dorsal  region  suffers  more  than  the 
lumbar.  The  lesions  in  the  lateral  and  anterior  columns  are  quite 
variable,  both  in  extent  and  position,  but,  on  the  whole,  resemble  those 
of  lateral  sclerosis. 

Tumors  of  the  Cord.- — Gliomata  are  the  most  frequent  tumors  of  the 
cord.  They  present  the  same  gross  and  microscopic  appearances  that 
characterize  similar  growths  affecting  the  brain.  The  effects  produced 
depend,  of  course,  on  the  size  and  situation  of  the  tumor.  Gliosarco- 
niata  also  occur.  Several  different  varieties  of  sarcomata  are  occasionally 
seen.  Secondary  carcinomata  and  sarcomata  are  sometimes  found. 
Tuberculous  lesions  and  gummata  may  occur,  but  are  quite  rare.  Cysts 
due  to  both  the  echinococcns  and  cysticercus  have  been  observed. 

Syringomyelia.^ — This  affection  is  characterized  by  the  formation 
of  one  or  more  cavities  in  the  cord.  The  most  frequent  seat  is  in  the 
cervical  enlargement,  in  the  vicinity  of  the  central  canal,  and  in  the  gray 
substance  of  the  posterior  commissure.  From  this  point  of  origin  the 
cavity  usually  extends  into  the  cornua.  The  white  matter  is  generally 
spared,  but  becomes  involved  when  the  destruction  of  the  cornua  is  more 
or  less  complete.  The  cavity  is  filled  with  a  liquid  analogous  to  the 
cerebrospinal  fluid.  According  to  some  writers,  the  excavation  results 
from  disintegration  of  an  embryonic  tumor  composed  of  neuroglia. 
Indeed,  in  a  number  of  cases  the  cavity  is  surrounded  by  a  mass  resem- 
bling gliomatous  tissue.  The  medullary  fissure  around  the  excavation 
is  compressed  and  the  cord  flattened ;  the  posterior  and  the  lateral  tracts 
usually  undergo  changes.  As  a  constant  clinical  phenomenon  should 
be  mentioned  the  sensory  dissociation  which  consists  of  loss  of  the  sense 
of  pain  and  temperature  and  preservation  of  touch.  Pain  and  tempera- 
ture sense  are  conducted  by  Gowers's  tract,  which  comes  from  the  oppo- 
site side  of  the  cord  and  traverses  the  white  commissure.  As  the  cavity 
in  syringomyelia  is  around  the  center  of  the  cord,  the  fibers  of  Gowers's 

'Russell,  "Clinical  Record"  (London),  Dec.  20,  1S99.  Crouzon,  "  Des  Scle- 
roses conibinees  de  la  Moelle,"   Paris,    1904. 

^  Hunter,  "Brain,"  Summer,  1902,  p.  226.  Collins,  "Med.  Record,"  December 
6,  1902.  Tytler  and  Williamson,  "Brit.  Med.  Jour.,"  Feb.  7,  1903,  p.  301.  Cush- 
ing,   "Annals  of  Surgery,"  June,   1904,  p.  934. 

^  Zappert,  "Wien.  klin.  Woch.."  Oct.  10,  1901.  Fleger,  "Wien.  klin.Woch.." 
1902,  Nos.  32,  33  and  34.  Kienbock,  "Jahrb.  f.  Psych.,"  1902,  xxi,  p.  50.  Bres- 
saud,  "Arch.  Gen.  de  Med.,"  1903,  No.  52.  Gowers.  "Lancet,"  Oct.  10,  1903,  p. 
993.  Thomas  and  Haixser,  "Nouv.,  Iconogr.  de  la  Salpetriere, "  1904,  tome  xvii. 
No.  6,  p.  376. 


THE    NERVOUS    SYSTEM,  889 

tract  arc  always  invulvcil.  Umlcr  the  niicrostopc,  besides  tlie  ylioma- 
tous  tissue  can  be  seen  debris  of  tlic  disorganized  nervous  tissue  in  the 
immediate  vicinity  of  the  cavity,  cells  of  the  cornua,  denuded  axis- 
ivlinders,  and  amyloid  bodies.  An  important  feature  of  syringomyelia 
is  the  secondary  degeneration  (p.  000)  of  various  tracts  which  depend 
ixpon  the  seat  of  the  lesion.     The  meninges  are  usually  intact. 

THE   NERVES. 

Nothing  of  importance  is  known  of  the  minor  circulatory  disturbances 
in  nerves.  It  is  probable  that  the  amount  of  blood  within  them  is 
influenced  in  a  greater  or  less  degree  by  the  same  causes  that  produce 
like  results  in  the  central  nervous  system;  the  ([uantity  of  blood  would 
certaiiih-  be  increased  in  the  active  stages  of  inflammation. 

Hemorrhage  into  the  nerves  results  from  injury,  and  is  sometimes 
seen  in  infectious  diseases,  especially  the  hemorrhagic  septicemias. 
A  considerable  part  of  the  nerve  may  be  inflltrated  by  blood  which  later 
undergoes  alterations  similar  to  those  described  when  discussing  hemato- 
myelia  (p.  880). 

Infiltrations  of  nerves  are  infrequent  and  of  little  clinical  importance; 
after  injury  and  following  infection,  calcareous  matter  is  occasionally 
deposited  within  the  nerve-trunk.  Fatty  infiltration  is  infrequent; 
irregular  collections  of  fat  are  sometimes  found  in  the  larger  nerves, 
and  such  fatty  masses  may  be  of  sufficient  size  to  justify  the  name 
lipoma.  After  degenerations  and  necroses  the  residual  tissue  of  the 
nerve  may  contain  pigment. 

Degeneration  of  the  nerves'  follows  any  lesion  which  dejjrives  the 
fiber  of  its  connection  with  the  ganglion  cell  (see  Wallerian  degeneration, 
p.  861  I.  Diseases  of  the  ganglion  cell  terminating  in  its  destruction  are 
followed  by  degenerative  changes  in  the  fiber  to  which  the  cells  give 
origin.  (See  anterior  poliomyelitis,  acute  and  chronic,  pp.  883  and  884.) 
Gradually  applied  pressure,  as  by  growing  tumors,  cysts,  and  inflam- 
matory- processes,  also  induces  degeneration  of  the  myelin  and  axis- 
cvlinder.  The  metamorphoses  resulting  from  infections  and  toxic 
conditions  are  usually  classed  with  the  inflammations  of  nerves. 

Inflammation  of  the  nerves  is  called  neuritis.  It  may  be  acute  or 
chronic:  in  .some  cases  a  single  nerve-trunk  is  involved,  and  in  other 
instances  a  large  number  of  the  nerves  are  aflected,  and  the  condition 
is  called  polyneuritis.  When  the  inflammation  tends  to  extend  from 
the  point  of  origin  toward  the  nerve-centers,  it  is  termed  ascending 
neuritis,  and  when  the  lesion  travels  in  the  opposite  direction,  descending 
neuritis. 

Inflammation  of  the  nerves  may  result  from  a  large  number  of  causes, 
all  of  which  can  not  be  enumerated  in  the  space  available.  Certain 
of  these  etiologic  factors  operate  locally;  among  this  group  must  be 
included  trauma,  extension  of  inflammation  from  contiguous  tissues, 
and  the  results  of  cold  and  exposure  when  manifested  in  a  single  nerve- 
trunk.  The  internal  causes  are  toxic  substances  affecting  the  nerve 
from  the  circulating  blood  and  lymph.  These  poisons  may  be  of  meta- 
bolic origin,  and  with  this  group  are  included  those  giving  rise  to  the 

*  Kattwinkel  and  Kerschensteiner.  "  Lubarsch  and  Ostertag's  Ergebnisse  der 
allg.  Path.  u.  path.  Anat.,"  Neunter  Jahrg.,  I  .'\bt,  1903,  p,  7. 


Sqo  special  pathology. 

neuritis  occurring  in  gout,  diabetes,  or  uremia.  Of  the  inflammations 
of  nerves  due  to  poisons  introduced  from  without,  those  resulting  from 
ptomain  and  other  types  of  food  poisoning,  alcohol,  and  the  acute  and 
chronic  intoxications  by  such  metals  as  arsenic,  copper,  and  mercury  may 
be  cited.     A  definite  group  of  nerve  inflammations  accompany  certain  in- 


t:*'-" ?-■■'■"        %!   .■'"'mm 

j;...-»rff«C;v..;..7;-:;<.'s;..-  ,v  f  ^^^  .  '■   '      :•.:{''.■•. 

v:-^:^?.;.:;]^?^ -■?:•_       ^.     ,  ^i;-.  x.;:  :^^^;^':.  ^'^i;^}:■:■^• 


b 


^5-:^ 
^S^:;' 


•.u  ■ 


#S&»v^'^ 


Fig  420. — Xerve.    Acute  Interstitial  Xeuritis. 
Fixed  in  Heidenhain's  solution;   stained  with  toluidin-blue  and  eosin.     a.  Xormal  nerve-fibers.     6.  Blood-vessels. 
c,  c,  c.  Collections  of  lymphoid  cells  between  the  nerve-fibers. 

fectious  diseases.^  The  nerve  lesion  of  anesthetic  leprosy  (p.  158)  is  a 
leprous  neuritis.  In  pyemia,  septicemia  and  other  mycoses  of  the  blood, 
inflammations  of  the  nerves  are  sometimes  observed.     Beri  beri-  or  kakke 

'  For  a  study  of  diphtheric  neuritis,  see  Aubertin,  "Centrabl.  f.  Kinderheilk.," 
vol.  ix.  No.  3;  Babonneux,  These  Fac.  de  Med.  Paris,  1904;  RoUeston,  ''Practi- 
tioner," November,  1904,  p.  597;  Butler,  "Med.  News,"  Jan.  21,  1905,  p.  117. 
For  typhoid  neuritis  consult  McCrea,  "Amer.  Med.,"  Sept.  26,  1903,  p.  503;  Pas- 
coletti,  "Gaz.  degli  Osped.  e.  delle  Clin.,"  March,  1904;  Keen,  '"Svirgical  Compli- 
cations and  Sequels  of  Typhoid  Fever,"  1898.  Tuberculous  neuritis,  Clement, 
"  Acad,  des  Science,"  Feb.  6,  1905;  "  La  Sem.  Med.,"  Feb.  15,  1905,  p.  79.  Syphil- 
itic neuritis,  Cestan,  "  Nouveau  Iconogr.  de  la  Salpetriere, "  1900,  xiii,  p.  153. 
Malarial  neuritis,  Luzzatto,  "Berl.klin.  Woch.,"  April  28,  1902,  p.  375.  Neuritis 
following  pertussis,  Eshner,  "Jour.  Amer.  Med.  Assoc,"  Jan.  10.  1903,  p.  88; 
also  Valentin,  These  de  Paris,  1903.  Neuritis  following  mumps,  Zahorsk}',  "In- 
terstate Med.  Jour.."  Sept.,  1903,  also  Dopter,  "Gaz.  des  Hop.,"  Aug.  2,  1904,  p. 
857.      Influenza,  Mix,  "Medicine,"  May,  1904. 

^  Luce,  "Arch.  f.  Schiffs-u.  Tropenhygiene,"  July,  1902.     Wright  and  McGill, 
Brain,"  Winter,  1903.      Uchermann,  "Zentralbl.  f.  inn.  Med.,"  June   18,   1904. 


THI-:   \i:Kvr)VS  systrm. 


891 


is  a  form  of  endoiiiic,  sometimes  epidcmir.  multiijlc  neuritis  fthserveil 
especially  in  China,  Japan,  certain  ])arts  of  India,  tlie  Philii)pinc  Islands, 
and  other  troj)ical  and  suV)tropical  countries.  Tiie  mc>st  common  f(jrm 
of  multiple  neuritis  is  that  caused  by  alcohol;  the  condition  may, 
however,  be  the  result  of  poisons  other  than  al(()hf)l  an<l  of  any  of  the 
infective  diseases. 

Morbid  Aiiiitotuy. — On  examination  the  inflamed  nerve — esj)ecially 
if  the  process  be  acute  and  of  a  decided  character — is  found  more  or  less 
reddened  and  swollen.  At  a  later  stage  the  nerve  may  shrink  to  a 
certain  extent,  owing  to  the  formation  of  fibrous  tissue.  On  micro- 
scopic examination  the  nerve  ])resents  changes  the  peculiar  character  of 
which  depends  upon  whether  the  fibers  or  the  interstitial  structures 
are  most  atTected;  the  former  variety  is  called  parcucliynialoiis  neuritis; 
the  latter,  interstitial  neuritis.  In  localized  neuritis  the  interstitial 
changes  are  usually  pronounced,  while  in  the  multiple  forms  the  invflin 
and  axis-cylimler  (parenchyma)  are 

primarily  involved.    Either  variety, - 

if  pronounced,  ultimately  gives  rise 
to  the  other. 


^^p 


:^ 


Fig.  4ai. — Longitudinal  SEcnoN  of  the  Muscclo- 
spiRAL  Nerve,  Removed  from  a  Man  who  Died 
AS  a  Result  of  Alcoholic  Multiple  Neuritis. 

Section  hardened  in  Miilli-r's  solution;  stained  t)y 
Weigcrt's  new  hematoxylin  method,  d,  a.  Show- 
ing reniaius  of  myelin  sheaths  of  nen'cs.  6.  Com- 
pound granule  corpu.scles.  (Queen  obj.,  i-in.' 
oc.  B.) 


Fig.  42J. — Neuritis  Due  to  Chronic  Lf.ad  Intoxi- 
cation.— (Gordon). 

Section  of  musculospiral  nerve.  Wrigert's  stain;  the 
dcgcncratifl  fibers  are  unstained.  The  v»-s.v;l  in 
the  left  upper  comer  of  the  illustration  contains 
a  nodule  of  arteriosclerosis. 


In  the  acute  stages  the  interstitial  form  shows  under  the  microscope 
fullness  of  the  blood-vessels,  more  or  less  swelling  of  the  tissue,  and  an 
accumulation  of  leukocytes  in  the  part;  these  cells  are  ])olymorphonu- 
clear  if  the  process  be  suppurative,  and  lymphoid  if  otherwise.  Slight 
extravasation  of  blood  may  occur.  These  changes  are  usually  localized 
along  the  course  of  the  track  affected,  though  they  may  be  dififused  with 
a  certain  degree  of  uniformity.  If  the  inflammation  be  severe,  the  nerve- 
fibers  begin  to  show  changes  that  may  be  either  inflammatory  or  degene- 
rative, it  is  difficult  to  say  which;  the  latter  view  is  generally  accepted. 
The  alteration  first  oliserved  is  a  breaking  up  of  the  myelin  into  irregular 
masses  that  may  or  may  not  be  connected  with  one  another  by  thin 
filaments  of  the  same  substance.  If  prepared  by  Marchi's  method  (p. 
853).    microscopic    sections    show    areas    of    fatty    change.     The    axis- 


Hoist.  ■■  Xorsk  Majj.  for  L:rjxevirlenskal)en,"  Oct.,  1004. 
Schiffs-u.  Tropenhyg.,"  Oct..  1901  H.l  viii  V^  > ->  r)"ri 
Jan.,  1904,  p.   112. 


Fajardo. 

in      '  ■   li  iiir 


Arch.   f. 

•f  "yg." 


S92 


SPECIAL    PATHOLOGY. 


cylinders  are  usually  interrupted  at  the  points  where  the  myelin  is 
divided.  The  nuclei  of  the  nerve-sheath  increase  in  number.  Gradu- 
ally, the  myelin  further  degenerates,  and,  in  many  parts  of  the  nerve- 
tibers,  entirely  disappears;  when  this  occurs,  the  primitive  sheath 
collapses,  and  ultimately  the  entire  nerve  may  be  destroyed,  being 
replaced  by  fibrous  tissue.  As  the  process  becomes  older  compound 
granule  cells  make  their  appearance  within  and  around  the  fibers.  If 
the  inflammatory  phenomena  be  slight,  the  nerve-fibers  do  not  suffer  to 
so  great  a  degree.  In  the  chronic  forms  the  fibrous  tissue  is  usually 
greatly  increased ;  this  condition  is  commonly  observed  in  the  peripheral 


Fig.  423.— Chronic   Interstitial    Neuritis,   Showing   Degeneration    in  Some  of  the  Nerve-fibers.— 

{Gordon.) 
The  interstitial  tissue  is  everywhere  increased  and  the  perineurium  thickened.     The  patient  had  arteriosclerosis. 

nerves  particularly  of  the  aged,  and  is  probably  the  result  of  arterio- 
sclerosis. 

Whether  the  neuritis  be  primary  or  secondary  the  similar  alterations 
are  observed  within  the  nerve-fibers  involved.  Degenerative  changes 
occur  in  the  muscles  supplied  by  the  diseased  nerves.  The  fibers  lose 
their  striation,  become  granular,  fragmented  and  eventually  fatty ;  the 
nuclei  of  the  sarcolemma  and  interstitial  tissue  increase  in  number,  and 
finally  absorption  of  the  degenerated  and  necrotic  elements  leaves  the 
affected  muscles  extremely  wasted.  The  condition  constitutes  one 
form  of  secondar}^  degeneration  of  muscle  (p.  788). 

Degenerative  changes  in  the  nerve-trunk  follow  various  spinal 
and  many  cerebral  lesions.  The  structural  alterations,  occurring  in 
the  nerves,  differ  in  no  way  from  those  described  in  connection  with 


THE    NERVOUS    SYSTEM.  893 

wliat  IS  called  inflammation.  The  interstitial  chani^'cs  arc,  of  course, 
but  slight  in  these  cases. 

Regeneration  of  Nerves.' — If  a  nerve  he  divided,  that  {)art  distal 
to  the  st)luti()n  in  coiiiinuity  undergoes  degeneration  (see  Secondary 
Degeneration,  p.  8O0).  Regenerative  elTorts  are  usuall\'  manifest 
within  a  few  days  following  the  receipt  of  the  injury.  With  regard  to 
the  essential  nature  of  the  changes  by  which  restitution  is  accomplished, 
two  views  have  generally  been  held.  According  to  one  of  these,  the 
regeneration  progresses  from  the  center  toward  the  peripher>',  and  is 
practicallv  entirely  dependent  upon  the  projection  of  new  fibers  from  the 
central  segments.  Those  who  hold  to  this  method  of  regeneration  no 
longer  denv  that  the  neurolemma  of  the  young  fibers  is  derived  from 
pre-existing  elements  of  the  distal  segment.  Ballance  and  Stewart 
have  reviewed  the  older  observations  and  conducted  an  elaVjorate  series 
of  experiments  which  seem  to  establish  the  peripheral  theory  of  nerve 
regeneration.  During  the  tirst  eighteen  hours  following  the  injury, 
leukocytes  invade  the  distal  fragment  and  also  the  proximal  seg- 
ment, the  latter  in  the  vicinity  of  the  wound  only.  By  the  third  day 
the  leukocytes  have  almost  disappeared  and  large  oval  and  vesicular 
connective-tissue  cells  become  numerous  throughout  the  distal  segment. 
These  elements,  assisted  by  the  proliferated  neurolemma  cells,  remove 
the  mvelin  apparently  by  phagocytosis  which  begins  about  the  fourth 
dav  and  persists  for  several  weeks.  By  the  second  or  third  day  the 
neurolemma  cells  begin  proliferation,  which  is  at  first  patchy  along  the 
course  of  the  distal  segment,  but  later  becomes  uniform.  By  the  second 
or  third  week  these  elongated  cells  form  columns,  and  by  the  fourth 
week  the  production  of  nerve-fibers  by  the  neurolemma  cell  is  evident. 
Within  twenty-four  hours  following  the  injun.'  a  primitive  end-bulb  is 
formed  on  the  distal  extremity  of  the  proximal  segment  and  is  due  to 
curling  of  the  divided  fibers.  After  the  preliminary'  degeneration  changes 
identical  with  those  occurring  in  the  distal  fragment  occur.  The  estab- 
lishment of  continuity  between  the  two  structures  is  accomplished  by 
neurolemma  cells  extending  across  the  defect  and  eventually  producing 
both  axis-cylinders  and  medullar}'  sheaths. 

Tumors  of  Nerves.- — The  most  frc(juent  neoplasms  affecting  the 
nerves  are  the  so-called  pseudoneuromata,  of  which  fibroucuromata  are 
the  most  common,  althouL^li  myxoneuromata  are  occasionally  observed. 
The  condition  called  neurofibromatosis  (p.  342)  is  manifested  by  numer- 

'  Ballance  and  Stewart,  "The  Healing  of  Nerves,"  1901.  Durante,  "  Nouv. 
iconogr.  de  la  Salp^tri^re,"  1903.  No.  6.  Henriksen,  "Lancet,"  April  11.  IQ03. 
p.  10 1 5.  Kennedy,  "Brit.  Med.  Jour.,"  Sept.  24.  1904,  ]).  729.  Powers.  "Annals 
of  Surger\',"  Nov.,  1904,  p.  633.  Langley  and  Anderson,  "Jour,  of  Physiol.." 
Aug.  22.  1904.  Schutte,  "Centralbl.  f.  allg.  Path.  u.  path.  Anat.,"  Nov.  30,  1905. 
Spiller  and  Frazier.  "Univ.  of  Penna.  Med.  Bull.,"  June,  1903. 

*  See  Neuromata,  p.  320;  also  Neurolihromatosis,  p.  x^2,  and  Tumors  of  the 
Brain,  p.  S75.  Anthony,  "Jour.  Amer.  Med.  Assoc.,  '  June  13,  1903,  p.  1630. 
Frankel  and  Hunt,  ".Med.  Record,"  June  13,  1903.  P-  O^S-  Thomas,  "Johns 
Hopkins  Hosp.  Bull.."  Aug.,  1903,  p.  204.  Cestan.  "Revue  Neurolog,"  Aug. 
15,  1903.  p.  745.  Durante.  "Nouv.  iconogr.  de  la  Salp^tri^re,"  Nov.  and  IVc, 
1903.  Noves,  "Jour  of  Path,  and  Bact,"  Dec,  19°.^  V  240.  Beiger,  "Arch. 
Gen.  de  Med.."  1904,  p.  1367.  Fabris,  "Arch,  jx-r  le  sc.  M^d.,"  1904.  fasc.  ii. 
Rudler.  "Nouv.  icono^.  de  la  Salpetriire."  May  and  June,  1904,  vol.  17.  Hulst. 
■  Psvchiatrische  und  Neurologische  Bladen."  1904,  May  and  June,  No.  3.  Bourc\ 
and'Laignel-Lavastine,  "Soc".  Mod.  des  Hup."  Jan.  \\.  100;.  Meek.  "Boston 
Med.   and  Surg.  Jour.,"    March   30,    1905. 


894  SPECIAL    PATHOLOGY. 

ous  tumors  distributed  in  the  peripheral  nerves.  Amputation  neuro- 
mata commonly  develop  on  the  ends  of  nerves  in  amputated  extremities ; 
Durante  has  reported  a  case  in  which  neoplasms  of  this  type  developed 
on  the  distal  end  of  the  proximal  segment  and  on  the  proximal  end  of 
the  distal  fragment.  The  tubcrcnla  dolorosa  or  painful  subcutaneous 
tubercle  is  usually  a  fibroma  surrounding  a  small  nerve  filament.  Car- 
cinoma and  sarcoma  sometimes  involve  nerves  distributed  in  the  tissue 
invaded  by  the  new  growth;  as  a  rule,  however,  these  structures  escape 
infiltration. 


PART  IV. 
APPENDIX. 

GENERAL  LABORATORY  TECHNIC 


PART  IV  (APPENDIX).— GENERAL   LABORATORY 

TECH  NIC. 


CIIAI'TI-R    I. 
BACTERIOLOGIC  TECHNIC 

In  order  satisfactorily  to  stiuh-  niicroorganisins  \vc  must  be  able 
to  secure,  and  if  possible  to  maintain,  pure  cultures,  a  term  to  be  ex- 
plained later.  The  soil  upon  which  bacteria  are  grown  is  called  a 
culture  mediu))i.  The  soils,  or  culture  media,  are  classed  under  two 
heads — the  natural  and  the  artificial ;  of  each  of  these  we  have  two 
kinds,  the  jiuid  and  the  solid. 

Natural  Culture  Media. — Fluid:  Blood-serum,  milk,  urine,  atjua  coca, 
hydrocele  fiuid,  eggs  or  egg-albumen,  etc.  Solid:  Blood-scrum,  eggs, 
potatoes  and  other  tubers,  and  fruits. 

Blood-serum  is  the  most  valuable  of  all  natural  culture  media, 
and  may  be  used  either  in  the  fluid  or  in  the  solid  state.  The  serum 
may  be  obtained  from  any  of  the  lower  animals,  though  that  of  the  calf 
or  ox  is  preferred.  The  blood  is  collected  in  clean  jars  at  the  time  of 
slaughtering;  a  gallon  fruit  or  museum  jar  answers  the  ])uq)ose.  If 
the  blood  is  passed  directly  from  an  artery  into  a  sterilized  jar,  it  will 
remain  sterile.  The  freshly  drawn  blood  is  allowed  to  coagulate  in  the 
sterile  receiver;  it  is  then  removed  to  the  laboratory.  A  sterile  glass  rod 
is  passed  around  the  outside  of  the  clot,  between  the  coagulum  and  the 
jar,  in  order  to  detach  the  fibrin  from  the  jar  and  to  [)ermit  the  clot  to 
contract.  The  jar  is  then  placed  on  ice.  In  from  twelve  to  twentv-four 
hours  the  clot  will  have  separated,  and  the  serum  may  be  drawn  off 
with  a  sterile  siphon.  If  it  is  clear,  it  may  at  once  be  placed  in  tubes;  if 
there  be  much  suspended  coloring-matter, — red  blood-cells, — it  may 
be  set  in  the  ice-box  for  .sedimentation,  after  which  the  clear  supernatant 
fluid  may  be  poured  into  the  culture  containers.  If  this  operation  be 
conducted  with  proper  care,  the  serum  should  not  require  sterilization, 
and  can  be  used  in  its  fluid  state.  In  order  to  avoid  infection  the  greatest 
care  must  be  taken  in  every  stage  of  preparation.  Containers,  pipets. 
instruments,  hands,  etc.,  must  be  sterilized  with  the  utmost  care  and 
maintained  in  an  aseptic  condition.  It  is  hardly  necessary  to  say  that 
such  extreme  care  can  rarely  be  taken,  .so  that  the  Councilman-NJallory 
method  (given  below)  has  practically  superseded  this  more  tedious 
process.  If.  however,  a  solid  medium  is  wanted,  the  serum  is  sterilized 
and  "set"  by  heating. 

In  order  to  sterilize  blood-serum  it  must  be  heated  one  hour  each 
day  for  four  days;  as  high  temperatures  cause  coagulation  of  the 
albumin,  the  heat  had  best  not  exceed  f)5^  C.     It  is  rendered  solid  by 

•  For  more  ck-taik-d  consideration  of  Bacleriologic  Tcchnic  sec  works  referred  to 
in  foot-note  i,  p.  8i. 

58  897 


S98  GEXERAL    LABORATORY    TECHXIC. 

gradually  raising  the  temperature  until  coagulation  is  just  sufficient 
to  solidify;  at  this  stage  it  is  slightly  opalescent,  of  a  yellowish  straw 
color,  and  easily  penetrated  by  a  needle.  The  temperature  necessary 
for  solidification  rarely  exceeds  70°  C.  Councilman  and  Mallory  avoid 
the  foregoing  tedious  process  in  the  following  manner: 

Blood  is  collected  in  a  clean  jar  and  permitted  to  coagulate ;  the  fibrin 
is  detached,  as  already  directed.  The  more  or  less  clear  serum  is  then 
siphoned  off.  The  small  amount  of  blood  present  does  not  interfere 
with  the  subsequent  handling  or  with  the  use  of  the  medium  for  culture 
purposes.  Previously  steriUzed  test-tubes,  prepared  as  directed  under 
Culture  Containers  (p.  903),  are  at  once  charged  with  the  fresh  serum 
and  placed  in  a  slanting  position  in  a  dry-air  sterilizer,  the  temperature 
of  which  is  raised  to  80°  or  90°  C.  The  heating  must  be  gradual,  and 
must  not  exceed  the  temperature  given.  As  soon  as  solidification  is 
complete  the  serum  is  transferred  to  a  steam  sterilizer  (the  tubes  being 
placed  on  end),  and  sterilized  at  100°  C.  for  thirty  minutes  each  day 
for  three  successive  days. 

LofBer's  blood -serum  mixture  contains: 

Bouillon  containing  one   per  cent,   glucose i   part. 

Blood-serum, 3  parts. 

The  two  are  mixed,  placed  in  the  tubes,  and  sterilized  as  directed 
for  blood-serum.  The  medium  is  especially  useful  for  the  Bacillus  diph- 
theriae.  but  may  be  used  for  almost  any  organism,  and  is,  taken  all  in  all, 
one  of  the  best  all-round  media  found  in  the  laboratory.  The  ad- 
vantages oft'ered  by  the  Councilman-Mallory  method  may  be  utilized 
in  the  preparation  of  this  medium.  The  formula  and  preparation  of 
bouillon  are  given  with  artificial  culture  media  (p.  900). 

For  a  number  of  purposes,  and  especially  for  cultures  of  gonococci, 
human  serum  is  useful;  it  may  be  obtained  from  blood  collected  by 
phlebotomy,  or  blood  expressed  from  the  human  placenta.  From  whole 
blood  it  is  prepared  as  already  directed  for  animal  serum.  Ordinarily, 
transudates  or  exudates  in  the  large  serous  cavities  are  collected  at 
autopsy  or  operation,  distributed  in  tubes,  sterilized,  and  if  necessary 
coagulated  in  the  same  manner  as  separated  serum.  All  fluids  with- 
drawn from  serous  cavities  do  not  contain  sufficient  albumin  to  solidify 
properly  by  heat;  such  fluids  must  be  used  in  a  liquid  form  or  solidified 
by  the  addition  of  gelatin  or  agar. 

Wertheim's  medium  is  prepared  by  adding  one  part  of  sterile,  freshly 
drawn  human  blood  or  blood-serum,  to  two  parts  of  liquefied  agar  at 
45°  C;  the  tubes  are  then  slanted  and  the  medium  allowed  to  solidify. 
Blood-smeared  agar  is  especially  useful  for  the  cultivation  of  the  in- 
fluenza bacillus;  it  is  prepared  by  smearing  a  few  drops  of  freshly 
drawn  sterile  blood  on  the  surface  of  agar  slants  which  should  be 
incubated  a  few  days  to  assure  sterility. 

Fresh  milk  normally  is  alkaline;  if  acid,  suspicion  must  be  enter- 
tained as  to  its  freshness.  .  For  use  as  a  culture  medium  the  cream  should 
be  removed  by  centrifugalization;  or  if  the  milk  be  placed  in  a  large 
container,  steamed  for  fifteen  to  twenty  minutes,  and  left  in  an  ice-box 
for  twenty-four  hours,  the  cream  will  rise  to  the  surface  and  may  be 
siphoned  off.  The  milk  is  then  filled  into  tubes  and  sterilized,  pref- 
erably by  the  fractional  method.     For  the  purpose  of  determining  the 


HACTKRIOLOGIC    T  HC  II  \  IC.  899 

production  of  acid'  or  alkali  by  bacteria,  litmus  milk  is  used.  This  is 
prepared  by  adding  to  each  liter  of  milk  loo  c.c.  to  150  c.c.  of  a  waterv 
solution  of  litmus  prepared  by  dissolvinj.?  ()  j^'rams  of  purifie<l  litmus  in 
1000  c.c.  of  water,  usin<j  heat  if  necessary,  followed  bv  filtration.  The  re- 
sulting? mixture  is  distributed  into  tubes  and  further  sterilized  by  the  frac- 
tional method.     Some  bacteria  coaj^ulate  the  casein,  others  pej>tonize  it. 

While  they  are  useful,  the  employment  of  urine,  a(|ua  coca,  and 
hydrocele  thiid  is  not  j^i^eneral. 

Boiled  potato  affords  a  splendid  culture  medium  for  the  j^Towth  of 
many  bacteria.  Potato  used  as  a  culture  medium  is  first  thorouj^hlv 
washed  in  water  to  remove  dirt,  then  in  a  i  :  1000  solution  of  corrosive 
sublimate,  followed  by  sterilized  water  for  ten  or  fifteen  minutes  to 
remove  the  mercury.  The  potato  is  then  cut  into  slices.  With  an  apple- 
corer  pieces  of  the  proper  size  are  cut  from  the  slices,  slipped  into  steril- 
ized test-tubes,  and  a  small  (juantity  of  distilled  water  is  added  to  pre- 
vent rapid  drying  after  sterilization. 

Instead  of  using  an  apple-corer.  the  ,—-, 

potato  may  be  cut  into  a  long,  pyra-  .^ 

midal  piece  resembling  a  gigantic  ex-  »  ^1 

clamation  point.     The  small  end  of  the  f  k^ 

pyramid  should  be  long,  and  project  -  jA    - 

downward  into  the  water  at  the  bot-      fig.  424.— Moist  >  «  Pr.TATr.  cll- 

torn  of  the  tube,  thus  preventing  desic- 
cation  or  tne  upper  part  ot  tne  piece.  no,ato  cuitun-s,  the  dish  is  sterilized  in  a 

upon  which   the   culture   will   be   made.  hot  air  surili/.er  and  allowed  t..  owl.     In  the 

rn\  ,  .  ...  l)oltom  IS  placed  a  hlotter.  moistened  with  a 

1  he    culture    tubes     containing     pieces  i  :  1000  s<jluli.m  of  corrosive  suWimalc.     The 

are  now  stenlized  by  placing  them  in  1!^^  lL^::^i^.'7Il!^,i^^:,Xt 

an      autoclave      for     from      tWentV       to  i;-  shown  on  page   iS.   is  also  slenliri-<l -.  the 

^  .  t         r  ■•  1  worker  thorou^nlv   di.sinleits   his   hands   and 

tWentV-nve  minutes  ;  or,  bv  fractional  takes  the  steHle  [xjnt..  in  the  Uft  hand  and 

<:tf>rili7atir.n      fnr     an     Viniir'a     rla\'      fnr  the  sterile  knife  in  the  rinht  hand;    the  ix.talo 

StenilZailOn,    lOr    an     nOUr  a    aa\  ,    lOr  ,s  tlu-n  incise.!  in  its  |on«i-st  diameter,  and. 

from    three    to    five     daVS.    in    a    steam  without  sep.ir.ilinK  the  two  hakes,  .m  assistant 

...  _,,  -  r-'ises  the  upper  half  of  the  di'-h  l,v  ihv  knoI> 

sterilizer.      Ihev   are   now   readv   for  while  the  potato  is  <iuirki  :.  the 

ir..-    ...1^4-i/-.n  '  '  .sterile  blotter,  the  two  hah.  ;cd 

inoculation.  sothat  the  fn-shlyincisclst-i  n.ijf 

Sterilized    eggs    are    occasionallv  '^  I"''"V''  VJ'*^'"'''  •*"•:  '"'  '-  ""\  f^kiy 

,    ,  ,  Pv  .  .  ,    .-  rcpi:ice<t.     It  no  Krowtn  occurs  on  the  ijotato 

used   tor   the    cultivation   ot    anaerobic  in  three  or  f.mr  davs,  it  mav   Im;  considered 

bacteria.         The     eggs     are     thoroughly  stenle.  and  may  l,c  inoculated. 

sterilized    at   a   low   temperature,   as 

already  directed  for  blood-serum,  a  point  in  the  shell  is  carefully  pene- 
trated with  a  sterile  borer,  the  egg  is  inoculated,  and  the  puncture  sealed 
with  wax.  (Jccasionally,  sterilization  may  not  be  necessary;  but  with- 
out it  incubation  can  not  well  be  applied,  as  the  chick  develops  too  rapidly. 
After  inoculation  the  egg  may  be  dipped  in  hot  paraffin,  which,  on  cool- 
ing, forms  an  air-tight  covering. 

Artificial  Culture  Media.* — l-'lnid :  Inorganic  solutions,  organic 
mixtures,  bouillon,  and  vegetable  and  animal  infusions.  Solid:  Bouillon, 
milk.  etc..  solidified  by  the  addition  of  gelatin,  agar-agar,  or  gelatin  and 
agar-agar.  To  cultivate  certain  bacteria. — the  tubercle  bacillus,  for 
instance. — it  may  be  necessar)*  to  add  glycerin  to  the  medium. 

'  For  method  of  estimatinjj  the  production  of  acid  by  bacteria  in  culture  see 
Hanna.  ■Jour,  of  Path.."  C)ctolTer.  iSqS.  p.  267. 

'  For  the  preparation  of  salt-free  culture-media  see  Taylor,  "Jour  of  Exjieri- 
mental  Med,"  Feb.  25.  iqos.  p.  iii. 


900 


GENERAL  LABORATORY  TECHNIC. 


The  most  useful  artiticial  culture  media  are  infusions  of  beef  and 
mutton  containing  a  small  quantity  of  peptone.  Most  of  the  bacteria 
develo])  (juite  readily  in  such  media.  The  stock  culture  media  is 
Koch's  alkaline-beef-peptone  bouillon.  For  ease  and  rapidity  of  prepa- 
ration the  following  is  recommended:  Take  an  ordinary  farina  boiler 
(agate-ware  is  best),  and  fill  the  outside  kettle  with  sufificient  water  to 
inclose  the  inside  can;  into  the  latter  put  one  liter  of  water,  which  had 
best  be  distilled;  with  a  diamond  or  file,  mark  on  the  side  of  the  can  the 
height  of  the  fiuid.  Marks  made  on  the  side  of  the  container  are  often 
difficult  to  find  or  to  difTerentiate  from  other  scratches,  particularly  when 
the  can  is  more  or  less  filled  with  steam  and  boiling  fluids.  An  equally 
efficient  and  somewhat  simpler  method  is  to  mark  upon  a  glass  rod  the 

depth  of  the  fluid,  subse- 
quently maintaining  the 
same  depth  by  the  addi- 
tion of  water.  Obtain  0.5 
of  a  kilogram  of  finely 
chopped  lean  beef  from 
which  the  fat  has  been  care- 
fully removed;  add  this  to 
the  water,  a  little  at  a  time, 
stirring  constantly  so  as  to 
make  sure  that  every  piece 


Fig.  425. — Instrument  for  Cutting  Plugs  of  Potato  for 
Potato  Cultures. 

The  cut  plugs  are  washed  in  water  and  pushed  down  into  test- 
tubes  into  which  the  potato  segment  fits  closely.  Enough 
water  is  added  to  come  just  up  to  the  lower  end  of  the  plug. 
The  tubes  are  then  sterilized  as  directed  in  the  text. 


Fig.   426. — Agate-ware  Water-bath 
(Farina  Kettle). 
Used  in  making  culture  media,  and  con- 
venient for  many  purposes  about  the 
laboratory;     the  capacity   should   be 
about  1000  c.c.  for  inside  boiler. 


of  the  meat  is  well  penetrated.  The  original  directions  required  that 
this  mixture  macerate  for  twelve  hours  before  proceeding  with  the  next 
step.  Usually  maceration  is  unnecessary,  although  some  workers 
apparently  always  macerate  for  twelve  or  twenty-four  hours,  as  originally 
advised.  Whether  macerated  or  not,  the  next  step  is  to  add  the  peptone 
and  salt.  Take  ten  grams  of  Witte's  dried  beef -peptone  and  five  grams 
of  salt  (sodium  chlorid),  and  mix  them  thoroughly  in  a  mortar  or  tea- 
cup; add  just  enough  water  to  rub  the  mixed  powders  into  a  thin  paste, 
which  is  now  added  to  the  meat-and-water  mixture  in  the  farina  kettle 
and  thoroughly  stirred  into  the  mass.  The  water  in  the  outside  kettle 
is  now  brought  to  a  boil,  during  which  time  the  mixture  in  the  inside 
kettle  has  been  frequently  stirred.  As  soon  as  the  albumin  begins  to 
coagulate  the  stirring  is  stopped,  and  when  coagulation  is  fairly  ad- 


RACTKkloLoC.IC    TKCIINir,  QOI 

vanceil — alter  litloen  or  twenty  minutes' boiling —llic  insi<le  kettle  is 
removed  from  its  surroumlini,'  \vater-l)ath  an<l  its  ef)ntents  boiled  over  the 
tiamc,  care  bcin.t;  taken  that  it  does  not  boil  over.  The  meat  and  eoaj^u- 
lated  albumin  collect  into  a  rather  dense  mass,  which  should  be  broken  up, 
so  that  the  interior  may  be  fully  {penetrated  by  the  boiling'  lluid  in  fjrder 
to  extract  the  salts  contained  in  the  meat.  After  thirty  minutes'  boilinj^ 
the  mass  is  removed  from  the  flame  and  strained  through  flannel.  The 
water  lost  by  evaporation  must  be  made  up  by  pourinj^  enough  cold 
water  over  the  meat  in  the  strainer  to  bring  the  filtrate  to  one  liter.  If 
anv  fat  is  seen  over  the  surface  of  the  fluid,  as  much  as  possible  is  re- 
moved with  a  spoon  or  by  gently  touching  it  with  j)aper  or  a  clean  cloth. 
The  filtrate  is  usually  clear,  and,  if  not,  it  must  be  filtered.  Tested 
with  an  indicator,  this  fluid  will  be  found  acid,  and  must  be  made 
neutral  or  faintly  alkaline.  This  is  best  done  by  adding,  drop  by  drop, 
a  ten  per  cent,  solution  of  caustic  soda  (sodium  hydroxid).  The  best 
indicator  is  a  phenolphthalein  solution,  made  by  dissolving  one  gram 
of  phenolphthalein  in  looo  c.c.  of  fifty  per  cent,  alcohol.  A  watch- 
glass  containing  about  i  c.c.  of  this  solution  is  placed  conveniently,  and 
into  this  a  drop  of  the  bouillon  is  mixed,  a  different  watch-glass  being 
used  for  each  drop;  as  soon  as  alkalinity  is  reached,  the  indicator  turns 
a  bright  rose-color,  which,  while  distinct,  should  be  faint.  Litmus  paper 
mav  be  used  for  the  same  purpose  but  is  less  delicate,  although  sufficiently 
accurate  for  routine  work.  With  the  disappearance  of  acidity  the  bouil- 
lon becomes  faintly  cloudy,  the  salts  and  albumins,  insoluble  in  an 
alkaline  fluid.  preciJDitating.  To  complete  the  formation  of  this  precipi- 
tate the  fluid  is  thoroughly  boiled  for  at  least  thirty  minutes,  and  then 
filtered.  It  is  advisable,  when  a  perfectly  clear  fluid  is  absolutely 
essential,  to  cool  the  medium,  filter,  reboil,  and  again  filter;  this  is 
rarelv  done,  and  is  useless  except  that  it  assures  the  medium  remaining 
clear;  after  each  boiling,  and  before  finally  filling  the  culture  vessels, 
the  alkalinity  of  the  fluid  must  be  tested,  for,  in  some  inexplicable 
manner,  a  fluid  previously  known  to  have  been  neutral,  or  even  alkaline, 
mav  become  acid.  When  finished,  the  resulting  fluid  is  known  as  neu- 
tral-, alkaline-,  or  acid-beef-peptonc  bouillon,  the  first  word  of  the  name 
alwavs  indicating  the  reaction.  When  intended  for  the  cultivation  of 
tubercle  bacilli,  glycerol  (glycerin)  is  added  (the  amount  commonly 
employed  is  six  per  cent.) — 60  gm.  of  the  glycerol,  which  must  be 
weighed  and  not  measured,  to  1000  c.c.  of  the  bouillon.  It  is  now 
known  as  alkaline-glycerin-beef-pcptone  bouillon. 

Instead  of  the  0.5  of  a  kilogram  of  beef  used  in  the  above,  two  grams 
of  meat  extract  (Liebig's  or  Armour's)  may  be  substituted.  The 
preparation  is  practically  the  .same,  except,  of  course,  the  flannel  filter 
is  not  needed,  and,  as  the  meat  salts  are  exceedingly  difficult  to  remove, 
filtering  while  hot.  and  again  when  cold,  may  require  frequent  repetition 
to  secure  a  perfectly  clear  fluid.  Media  j)repared  with  an  extract  are  not 
so  satisfactory  as  those  made  from  the  beef  direct.  Streptococci  grow 
indifTerently  or  not  at  all  upon  media  prepared  from  commercial  extract. 

When  it  is  desired  to  render  the  foregoing  solid,  gelatin  or  agar,  or 
both  coml)ined,  may  be  used. 

Beef-peptone-gelatin. — To  1000  c.c.  of  cold  bouillon  add  100  gm. 
of  gelatin  (gold-leaf,  in  sheets),  torn  or  cut  into  fragments;  macerate 
for  fifteen  or  twentv  minutes,  until  the  gelatin  swells  up  and  becomes 


902  GENERAL  LABORATORY  TECHXIC. 

flaccid;  it  is  then  easily  dissolved  by  gently  heating  in  a  water-bath; 
bv  the  time  it  has  reached  a  temperature  that  will  not  scald  the  fingers 
the  gelatin  will  be  dissolved.  It  is  now  removed  from  the  water-bath 
and  cooled  until  the  fingers  can  be  comfortably  held  in  it  for  some  time 
— about  50°  C.  or  lower.  When  the  gelatin  is  thoroughly  dissolved,  the 
fluid  will  require  realkalinization;  as  gelatin  is  constantly  acid,  the  reac- 
tion of  the  previously  alkaline  bouillon  is  changed.  The  alkalinization 
must  be  most  carefully  done,  otherwise  the  gelatin  may  fail  to  solidify 
when  finished.  Again,  one  must  be  sure  that  all  the  gelatin  is  dis- 
solved before  alkalinization  or,  later,  the  reaction  may  be  found  acid. 
It  must  be  but  faintly  alkaline.  If  by  accident  the  fluid  be  made  too 
alkaline,  a  few  drops  of  dilute  acetic  acid  will  correct  the  error.  When 
the  reaction  is  satisfactory,  the  white  and  finely  broken  shell  of  two  eggs 
is  thoroughly  mixed  with  the  gelatin ;  this  is  heated  to  the  boiling-point 
in  a  water-bath,  followed  by  boiling  over  the  naked  flame  (which  is  best 
distributed  by  wire  gauze)  for  at  least  half  an  hour;  the  water  lost  by 
evaporation  is  made  up,  and  enough  of  the  mixture  filtered  to  half  fill 
a  good-sized  test-tube;  this  is  boiled  repeatedly  for  several  minutes,  to 
see  that  all  the  albumin  is  coagulated,  the  reaction  as  desired,  and  that 
the  gelatin  remains  clear;  if  so,  the  remainder  is  filtered  and  placed  in 
test-tubes.  When  properly  made,  gelatin  is  the  clearest  solid  medium 
at  present  attainable.  It  is  liquid  at  temperatures  above  22°  C,  and  can 
not,  for  this  reason,  be  incubated.  As  some  bacteria  liquefy  gelatin 
and  others  do  not,  it  constitutes  a  test  culture  medium  of  the  greatest 
value. 

Beef-peptone-agar, — Agar-agar  is  a  gelatinizing  agent  derived  from 
a  Japanese  seaweed.  It  is  used  for  making  culture  media  solid  in  the 
following  manner:  To  1000  c.c.  of  bouillon  add  ten  grams  of  the  agar 
threads  cut  into  fragments  not  over  two  centimeters  in  length ;  place  at 
once  to  boil  over  the  naked  flame,  stirring  frequently  to  prevent  burning 
and  the  threads  adhering  to  the  bottom  of  the  pan.  It  usually  requires 
about  an  hour  to  secure  perfect  solution,  without  which  filtration  is 
impossible.  Longer  boiling  does  no  harm,  the  quantity  of  the  medium 
being  maintained  by  adding,  from  time  to  time,  enough  water  to  com- 
pensate for  that  lost  by  evaporation.  When  fully  dissolved,  it  is  filtered. 
As  it  filters  with  much  more  difficulty  than  gelatin,  and  as  the  same 
precautions  are  necessary,  I  have  deferred  the  description  imtil  now. 
An  efficient,  heavy,  preferably  already  folded  filter  (machine-folded 
filters  are  by  far  the  best)  is  carefully  opened  and  adjusted  in  the  funnel; 
then,  with  the  greatest  care,  thoroughly  moistened  with  boiling  water; 
a  moment  is  allowed  for  the  contraction  of  the  filter,  which  always  takes 
place;  it  is  then  again  moistened  with  boiling  water,  the  excess  poured 
off,  and  the  agar  or  gelatin  poured  down  a  glass  rod  on  to  the  side  of  the 
filter — not  into  the  center  and  never  rapidly,  as  either  may  break  the 
paper.  In  the  case  of  agar  it  is  best  to  have  it  boiling  and  add  but  250  c.c. 
or  less  to  the  filter  at  one  time,  keeping  the  remainder  hot  in  the  water-bath 
and  heating  to  boiling  just  before  pouring  into  the  filter.^  Gelatin  can 
not  be  boiled  very  long  or  it  may  fail  to  gelatinize ;  with  agar  this  danger 
is  not  present.  Gelatin  burns  to.  the  pan  unless  carefully  watched; 
agar  may  do  so,  but  less  frequently.     Gelatin  should  always  be  cleared 


scop 


'  Foi;  other  methods  of  clarifying  agar  see  Alleger,  'Jour,  of  Applied    Micro- 
y,"  January,  1898;   also  Carter,  "Jotir.  of  Applied  Microscopy,"  April,  1898. 


bacti;ki(jL()c;ic  thciinic. 


903 


by  an  eg^;     ai^ar  may  be.  but  does  not  require  it.     A^ar  soliilirtes  at 
about  42°  C.  and  melts  only  near  the  boiling-point;    it  is  not  so  clear 
as  ji;elatin.  but,  as  it  can  be  iTUubated,  has  many 
advantaj^'cs.      It    remains   solid    when    prepared 
with  glycerin  bouillon,  which    .ijelatin  does  not 
always  do. 

Urine  n^ur,  which  is  particularly  useful  ior  the 
cultivation  of  the  i^onococcus,  is  made  by  usin)^ 
urine  instead  of  bouillon.  The  urine  is  neutra 
lized  or  rendered  faintly  alkaline,  or  it  may  be 
used  in  its  acid  condition.  ( )ne  per  cent,  of  pep- 
tone and  0.5  per  cent,  of  salt  may  be  added, 
althoui^h  this  is  not  ordinarily  necessary.  After 
filtration,  preliminary  boiling, and  filtration  while 
hot  and  again  when  cold,  the  agar  is  added,  clis- 
solved,  and  filtered  as  already  directed.  For  the 
preparation  of  agar  media  containing  blood  and 
blood-serum  see  page  SqS. 

Culture  Containers. — Cultures  may  Vje  made 
in  bottles,  flasks,  or  test-tubes ;  the  last  two  are  the  most  used.    If  perfectly 
new,  a  thorough  rinsing  in  clean  water  will  suffice;  if  the  tubes  have  con- 


FiG.  427.— Test  xrBK    Basket, 
NlAnE   OF  Tinned   Metal, 
FOR  HoLDisr.  Test-tubes. 
These  baskets  should  Ix?  uk  by 
100  mm.,  and  150  mm.  high. 


4.-  ili>T-Ai«   Stekiuze>,  ro« 

Stkkim/in  i>-i  I' itrs.  Olas-^ware,  a.vd 
Other  Laburatijry  .Appliances  and  I.nsthi'- 
ments. 


Fig.  4>o. — Diaguam  of  Interior  of  Mot  air  Ster- 


The  con" 

■lUH' 

an  efju.ii  .iiMnh 


'i.n  c'l  tic.n  II 


..ri  u(  hot  air 
rrbjr  asourrs 
inirrior. 


tained  cultures,  or  have  in  them  cultures  either  growing  or  dead,  they 
should  be  placed  in  the  sterilizer  for  a  couple  of  hours,  with  the  cotton  plugs 
in  place;  remove  from  sterilizer,  take  out  the  l)lugs.  pour  out  thet-ontents 


904 


GEXERAL    LABORATORY    TECHXIC. 


of  tlie  tubes,  and  boil  one  hour  in  a  two  per  cent,  solution  of  washing  soda ; 
wash  with  test-tube  brush  and  rinse  in  several  changes  of  clean  water; 
rinse  in  a  one  per  cent,  solution  of  hydrochloric  acid;  carry  through 
several  changes  of  water,  and  dry  with  bottom  upward.  When  dry,  plug 
with  cotton;  for  this  purpose  ordinary  cotton  batting,  clean  and  free  from 
the  cotton  hulls,  is  used.  Absorbent  cotton  possesses  no  advantages. 
A  more  or  less  square  or  octagonal  disc  of  cotton,  about  ten  centimeters 
in'  diameter,  has  its  corners  folded  into  the  center  so  as  to  make  a  plug 
twice  as  long  as  the  diameter  of  the  tube  or  the  neck 
of  the  flask.  The  plug  should  fit  so  tightly  that  the 
tube  or  flask  can  be  lifted  safely  by  the  cotton  plug, 
which  should  enter  the  mouth  to  a  distance  equal  to 
twice  the  diameter  of  the  tube  or  the  neck  of  the 
bottle  or  flask,  and  should  project  at-least  one  centi- 
meter. 

The  test-tube  used  for  cultures  should  be  of  the 
best  Bohemian  glass,  with  a  lumen  of  13  mm.  to  15 
mm.,  and  130  mm.  to  150  mm.  in  length.  The  best 
flasks  are  of  the  Erlenmeyer  form,  with  a  capacity 
of  100  c.c.  Larger  sizes,  250  c.c.  to  1000  c.c,  will 
be  needed  for  storing  media. 

After  cleaning  and  plugging,  the  tubes  and  flasks 
are  put. in  the  hot-air  sterilizer  for  twenty  minutes 
at  130°  C.  In  the  absence  of  a  hot-air  sterilizer  any 
cooking  oven  may  be  used,  leaving  the  tubes  in  the 
oven  until  the  cotton  just  begins  to  brown,  approxi- 
mately 140°  C.  The  tubes  are  now  ready  to  receive 
the  medium.  By  means  of  a  perforated  cork  and  a 
short  glass  tube,  a  rubber  tube  ten  centimeters  long 
is  attached  to  the  tubulature  at  the  bottom  of  an 
ordinary  percolator  or  funnel ;  at  the  lower  end  of 
the  rubber  tube  a  second  glass  tube  is  connected  so 
that  it  projects  about  ten  centimeters  below  the 
rubber  tube ;  the  latter  is  then  collapsed  by  means 
of  a  thumb  pinch-cock  (Mohr's  spring  pinch-cock) 
applied  to  the  rubber  tubing  between  the  ends  of  the 
two  glass  tubes.  The  liquefied  medium  is  poured 
into  the  percolator ;  the  test-tubes  are  then  arranged 
in  the  baskets  at  the  side  of  the  percolator.  A  test- 
tube  or  flask  is  grasped  by  the  left  hand,  preferably 
by  the  thumb  and  index-finger;  the  cotton  is  rotated 
and  loosened  by  means  of  the  thumb  and  index- 
finger  of  the  right  hand,  and  removed  by  grasping 
the  projecting  tip  between  the  ring-  and  little  fingers  of  the  right 
hand;  the  tube  is  now  carefully  slipped  over  the  filling  tube  from  the 
percolator,  care  hein^  taken  that  no  fluid  comes  in  contact  with  that  portion 
of  the  tube  into  which  the  cotton  plug  is  to  go;  relax  the  pinch-cock  and 
admit  to  the  test-tube  or  flask  the  desired  quantity;  close  the  pinch- 
cock,  remove  the  tube,  using  the  same  care  to  avoid  \uetting  the  mouth  of 
the -tube,  and  reinsert  the  cotton  plug.  This  is  repeated  until  the  desired 
number  of  tubes  or  flasks  are  filled.  If  any  of  the  medium  remains,  it 
may  be  run  into  a  flask,  sterilized  as  will  be  directed  later,  and  preserved 


Fig.  430. — Tube  Filler. 
Apijaratus  to  be  attached  to 
the  lower  end  of  a  funnel, 
as  shown  in  the  cut,  for 
use  in  filling  test-tubes. 
The  outside  glass  tube 
prevents  the  medium  that 
flows  from  the  in.side  tube 
from  coming  in  contact 
with  the  mouth  of  the 
test-tube  during  intro- 
duction or  withdrawal. 
A.  Mohr's  spring  pinch- 
cock. 


BACTKkUii.i  >i.U     TKCHMC 


QO: 


lor  tuture  use.  The  amount  of  medium  i>lace<i  in  each  iuL>e  varies  with 
the  medium  and  the  pur])ose  for  which  it  is  intended.  For  some  ex- 
periments a  measured  (juantity  will  he  needed,  hut  for  ordinary  purjjoses 
the  tube  should  be  aV)out  half  tilled  with  l)ouillon  orj^elatin,  and  with  agar 
to  a  depth  equal  to  a  little  more  than  twice  tlie  diameter  of  the  tube. 
Flasks  should  never  be  more  than  half  full  when  intended  for  culture, 
and  often  verv  much  less  will  be  sufficient. 

Sterilization. — The  Arnold  steam  sterilizer  or  the  autoclave  is  used. 
If  the  former  is  selected,  fractional  sterilization  is  best,  keepinjj  filled  tubes 
in  the  steam  chamber,  at  loc  C.  tliirt\-  minutes  a  day  for  three  succes- 
sive davs;  in  the  intervals  between  sterilizations  they  are  kept  at  room- 
temperature.  The  object  of  this  is  to  destroy  all  organisms  in  the  adult 
or  fully  developed  stage.  It  is 
known  that  spores  are  not  <ie- 
stroyed  by  a  temperature  of  loo"^ 
C.  unless  it  be  very  long  applied ; 
any  spores  escaping  the  heat  on 
the  first  day  are  given  time  to 
develop  by  the  second  day,  or.  to 
assure  their  being  killed,  a  third 
sterilization  is  practised.  Ex- 
perience teaches  that  this  is 
usually  sufficient ;  however,  the 
tubes  should  be  watched  for 
three  or  four  days,  and  if  any  of 
them  show  a  growth,  the  process 
should  be  repeated  for  all. 

By  means  of  the  autoclave  a 
temperature  of  130^  C.  is  ob- 
tained in  the  steam  chamber, 
which,  in  from  twenty  to  thirty 
minutes,  destroys  both  fully 
developed  bacteria  and  their 
spores :  it  is  of  great  convenience 
for  bouillon,  agar,  potatoes,  milk, 
and  many  other  culture  media, 
but  can  not  be  used  for  blood- 
serum  or  gelatin.  The  latter  usu- 
allv  fails  to  gelatinize  after  being 

subjected  to  the  high  temperature;  indeed,  gelatin  must  always  be  steril- 
ized with  the  greatest  care,  as  prolonged  exposure,  even  to  the  temperature 
of  100^  C,  should  be  avoided.  Potatoes  reijuire  prolonged  exposure  to 
high  temperature,  as  they  usually  contain  earth  organisms  difficult  to 
destrov. 

Slant  Cultures, — In  order  to  increase  the  surface  area  of  media  con- 
taining agar  or  blood-serum,  the  tubes,  while  the  medium  is  in  a  liquid 
state,  are  inclined  with  the  mouth  just  high  enough  to  prevent  the  agar 
flowing  up  to  the  cotton;  when  "set,"  they  may  be  stood  on  end,  as  other 
tuV)es. 

To  Prevent  Stored  Media  from  Drying. — For  this  ])urpose  the  writer 
has  tried  rul»bor  caps,  rubl-cr  tissue,  oiled  paper,  cork  and  rubber 
stoppers,  and  the  paraffin  method,  none  of  which  seems  fully  satisfactor>-. 


Fig.  431.— .Vrnold's  Stkam  Stkkilizeb.  Boston  Board 

or  Hlxlth  Form. 
This  is  the  most  convenient  and  the  best  steriliier  for  gen- 
eral laborator>'  purposes. 


906 


GENERAL  LABORATORY  TECHNIC. 


One  of  the  best  methods  is  to  trim  the  cotton  even  with  the  top  of  the 
tube,  and  push  it  down  0.5  cm.  below  the  tube-hp;  take  a  coin  of  proper 
size  to  drop  just  inside  the  hp  of  the  tube;  heat  the  lip  of  the  tube  and 
the  body  of  the  tube  as  far  down  as  the  cotton  extends,  until  the  cotton 
is  slightly  browned,  and  at  the  same  time  heat  the  coin;  drop  the  coin 
upon  the  tube,  and,  while  still  warm,  seal  it  to  the  tube  at  the  margin, 
using  for  this  purpose  a  good  quality  of  stationer's  sealing-wax.  This 
process  is  tedious,  and  is  most  useful  for  tubes  containing  cultures  that 
require  long  incubation,  such  as  the  tubercle  bacillus.     A  much  more 

useful  plan,  and  one  almost  as 
efficient,  consists  in  pushing  the 
cotton  down,  heating  the  mouth 
of  the  tube  and  inclosed  cotton, 
and  placing  over  the  end  a  disc 
of  quite  thick  tin-foil,  which  is 
evenly  folded  over  the  lip  of  the 
test-tube.  For  this  purpose 
commercial  tin-foil,  which  con- 
tains a  relatively  large  propor- 
tion of  lead,  may  be  used,  as  it 
is  much  cheaper  than  chemically 
pure  tin.  Such  a  cap  is  easily 
removed  and  replaced.  It  offers 
all  the  advantages  of  rubber, 
and  can,  if  sufficiently  heavy, 
be  readilv  sterilized. 

Dunham's  Peptone  Solution. 
— Rub  up  in  a  mortar  five  grams 
of  salt  and  ten  grams  of  peptone, 
with  enough  water  to  make  a 
paste;  finally,  dilute  to  1000  c.c, 
boil,  and  filter.  As  a  rule,  the 
filtrate  is  neutral  or  alkaline ;  in 
either  case,  after  sterilizing  as 
already  described  for  bouillon, 
it  is  ready  for  use. 

For  plating  it  is  always  best 
to  have  on  hand  a  number  of 
tubes  of  gelatin  and  agar,  each 
tube  two-thirds  full. 

Pure  Cultures. — A  pure  cul- 
ture is  one  containing  the  pro- 
geny of  a  single  germ ;  for  example,  a  pure  culture  of  the  tubercle  bacillus 
must  contain  no  other  germ.  When  two  kinds  of  bacteria  are  growing 
together,  the  growth  is  said  to  be  a  mixed  culture.  Under  nearly  all 
conditions  various  organisms  are  found  together,  and  in  order  to  separate 
them  we  must  resort  to  plating.  The  object  to  be  attained  is  the  separa- 
tion of  each  germ,  in  order  to  enable  it  to  develop  a  colony  by  itself;  so 
that,  if  the  original  mixture  contained  three  kinds  of  bacteria,  we  may 
obtain  three  kinds  of  colonies,  and  from  these  obtain  cultures  which  have 
but  the  one  variety — that  is,  a  pure  culture  of  each. 

Bottle   Plates. — Any   strong,    clear,    flat-sided   bottle   will   do.     The 


2pi^~^ 


Fi 


432- 


.\lTOCI.AVK,  OR  DlGESTOR,  USED  FOR  StERILIZ- 

i.NG  BY  Steam  U.vder  Pressure. 
The  lid  is  held  in  place  by  three  winged  nuts,  which  are 
thrown  down  to  the  side  in  order  to  raise  the  lid.  The 
solid  copper  chamber  on  the  inside  has  placed  in  it  two 
liters  of  water,  and  the  material  to  be  sterilized  is  placed 
upon  the  tray  with  perforated  bottom  shown  at  the  side 
of  the  cut;  this  is  then  placed  inside  of  the  autoclave, 
and  the  lid  is  closed  down  and  secured  by  the  winged 
nuts;  the  gas  is  now  lighted  and  the  heat  applied  until 
steam  escapes  from  the  small  cock  at  the  left,  which  is 
then  closed.  The  pressure  within  the  apparatus  now 
rises  until  the  safety-valve,  which  may  be  set  at  any 
pressure,  blows  off.  Sterilization  by  this  means  may  be 
secured,  at  temperatures  ranging  from  100°  C.  to  140° 
C,  in  from  twenty  to  forty  minutes. 


1   :   ' 


HAt'TKKlDl.iK.K      ri;(  iiMC.  907 

capacity  should  bo  about  500  c.c. ;  clean.  pluK  with  cotton,  and  sterilize 
in  hot-air  stcrili/.cr;  charj^'c  with  j^'clatin  or  aj^ar,  usually  about  twenty 
cubic  centimeters.  Sterilize  as  already  directed  for  lulture  media,  and 
set  the  bottle  aside  until  wanted  for  platinj.,';  to  prevent  the  medium 
from  dryin.ij.  the  cotton  may  be  pushed  downward  in  the  neck  so  as  to 
admit  a  short  rubber  stopper,  or  the  neck  ami  lip  may  be  covered  with 
tin-foil  as  already  directed.  As  a  rule,  the  bottle  will  be  used  within 
one  month,  durinj^  which  time  it  should  not  become  dry.  When  ready 
for  use.  at  least  three  bottles  will  be  needed.  bi(|uefy 
the  medium  in  the  sterilizer  or  water-bath;    cool  to  -,^.3 

50°  C.  or  l)elow.  inoculate  the  Hrst  bottle  with  a  small  Wi 

loopful  of  the  mixed  culture  or  suspected  material,  as  .jtJF^"^^*. 

pus  or  blood,  replace  the  cotton  plug,  and  shake,  to  m|^lHH 

thoroughly  mix;  inoculate  the  second  bottle  by  carry-  i!     .    I 

ing  a  loopful  from  the  hrst  to  the  second,  rejjjace  the 
plug,  and  shake;  and  in  the  same  manner  inoculate  a 
third  bottle  from  the  second,  and  shake  as  before. 
Lav  the  three  bottles  on  the  flat  side;  the  medium  will 
spread  out  and  cover  the  side  of  the  bottle;  label  the  ^^j  ^^,^..  - 

three  bottles  ii,  h.  and  c,  the  first  being  a.  "'    • 

Petri  Dish  Plates. — Three  or  more  test-tubes  con-      Vu..  4,,.^.    ui.akk  Bot- 
taining  sterile  agar-agar  or  gelatin,  filled  to  within  an  bottle *"  Pi'ates*— 

inch  or  so  of  the  cotton,  as  already  directed,  are  placed  (Copiin  and  Unan.) 

in  a  water-bath  or  a  sterilizer  and  the  contained 
medium  liquefied;  while  this  is  in  progress  an  equal  number  of  Petri 
dishes  are  sterilized  in  the  hot-air  chamber  and  allowed  to  cool.  The 
liquerted  medium  is  cooled  to  below  50°  C.  A  tube  is  inoculated  with 
the  material  to  be  plated,  as  directed  for  bottles;  from  the  first  tube 
a  second  is  inoculated,  and  from  the  second  a  third,  and  so  on.  each  tube 
having  the  medium  thoroughly  mixed  V)y  using  the  incjculating  needle 
as  a  stirrer.  Remove  the  cotton  from  the  first  tube  and  pass  the  lip  of 
the  tube  through  the  flame;  raise  the  lid  of  a  sterile  Petri  dish  just 
enough  to  get  the  mouth  of  the  tube  under  it.  and 
quicklv  pour  the  contents  of  the  tube  into  the  dish, 
which  is  then  gently  tilted  from  side  to  side  in  order 
to  distribute  the  medium  uniformly.  A  second  dish 
receives  in  the  same  way  the  contents  of  the  second 
tube,  and  so  on,  through  as  many  tubes  as  may  be 
i-iG.  4,4    i'l^ii  in^-vu      desired.     The  plates  are  labeled  as  directed  for  the 

BY   Petri.  ' 

Use<I  almost  cxclu.sivi-ly  for        OOttlCS. 

piatinK,  ihc  m.wt  con-  Esmarch's  Tubc   Plates. — Three    or   more    tubes 

vrnifnt     fliamclcr     i.<  .  .,  ,        .  ,  ,  .  ^     •     • 

from  looio  ijomm.  of  stcrilc  agar  or  gelatin,  each  tube  not  contammg 
more  than  two  or  three  cuf)ic  centimeters  of  the 
medium,  are  liijueHed  and  inoculated  as  directed  for  the  Petri  dish 
method.  A  channel  is  made  on  the  upper  nearly  flat  surface  of  a  block  of 
ice  bv  laying  upon  it  a  test-tube  of  the  same  size  as  those  to  be  used, 
filled  with  hot  water  and  corked,  the  stoppered  end  projecting  beyond 
the  edge  of  the  ice;  this  tube  is  rolled  over  and  over  in  the  same  spot 
until  the  channel  half  buries  it.  the  bottom  being  a  little  lower  than  the 
corked  end.  Into  this  groove  one  of  the  infected  tubes  is  laid  so  that 
the  medium  tlrjws  up  to  within  two  centimeters  of.  but  dovs  not  touch, 
the  cotton;    the  tube  is  then  rolled,  at  first  slowly,  then  more  quickly, 


f 


9o8  GENERAL    LABORATORY    TECHNIC. 

until,  within  the  first  minute,  it  is  spun  rapidly;  the  medium  in  this  way 
is  congealed  over  the  entire  inside  of  the  tube  nearly  up  to  the  cotton; 
if  the  latter  comes  in  contact  with  the  medium,  it  prevents  easy  removal 
of  the  plug  bv  making  it  stick  to  the  side  of  the  tube.  Each  tube  is 
treated  in  the  same  way,  after  which  it  is  labeled  as  directed  for  other 
plates.  When  set,  the  tubes  are  placed  on  end.  With  gelatin  this  can 
be  done  quickly;  with  agar,  however,  the  tube  must  be  kept  in  a  nearly 
horizontal  position  for  several  hours,  generally  overnight,  otherwise 
the  agar  may  slip  down. 

After  the  plates  are  made  by  either  of  the  foregoing  methods  growth 
of  the  bacteria  is  awaited;  agar  may  be  incubated.  At  the  end  of  a 
varving  period  the  colonies  appear  as  distinct  dots  in  and  on  the  culture 
medium.  In  plate  a  they  are  commonly  too  close  together  to  be  distinct ; 
plates  b  and  c  will  be  better.  Select  an  isolated  colony  and  transplant 
into  a  test-tube  in  the  following  manner: 

Heat  to  redness  the  entire  length  of  the  platinum  needle,  at  the  same 
time  exposing  to  the  flame  all  of  the  glass  rod  that  is  likely  to  enter  the 
test-tube,  bottle,  or  dish.  If  the  colony  to  be  removed  is  within  a  bottle 
or  test-tube,  it  is  best  to  bend  the  tip  of  the  inoculating  wire  like  the 


Fic.  435. — Platinum  Inoculating  Needles  Mounted  in  Glass  Rods. 
Showing  the  shape  of  the  ends  as  may  be  found  useful  for:  a,  stab  cuhures  and  stroke  cultures  ;   h  and  c,  stroke 

cultures  and  smear  cultures. 

letter  L;  immediately  after  sterilizing  the  needle,  holding  it  like  a  pen 
in  the  right  hand,  take  the  bottle  and  test-tube  or  both  test-tubes  in  the 
left  hand;  remove  the  plugs  from  the  tubes  or  bottles  by  grasping  the 
projecting  cotton  of  both  tubes  between  the  middle  finger  and  ring- 
finger  and  the  ring-finger  and  little  finger  of  the  right  hand;  pass  the  lip 
of  the  bottle  or  tube  through  the  flame  to  burn  off  any  adhering  dust; 
introduce  the  needle  into  the  bottle  or  tube,  and  lightly  touch  the  colony 
from  which  it  is  desired  to  obtain  a  culture;  this  will  infect  the  needle; 
quickly  withdraw  the  needle  and  pass  it  into  the  tube  containing  the 
medium  to  be  inoculated.  The  inoculation  made  may  be:  (a)  a  streak 
or  stroke  culture,  in  which  case  the  needle  is  drawn  from  below  upward 
in  a  straight  line  over  the  slanting  surface  of  an  agar  or  blood-serum 
tube;  (b)  a  smear  culture,  made  by  gently  rubbing  the  infected  wire 
over  the  surface  of  the  medium;  or  (c)  a  stab  culture,  made  by  a 
straight  needle-thrust,  from  above  downward,  through  the  medium. 
Stroke  and  smear  cultures  are  the  most  used  on  all  solid  media  except 
gelatin,  in  which  stab  cultures  are  best.  In  transplanting  from  a  Petri 
dish  culture,  the  lid  is  raised  barely  enough  to  introduce  the  prev- 
iously sterilized  needle,  which  is  then  touched  upon  the  colony,  re- 
moved, and  applied  to  the  culture  tube  as  previously  directed. 


B  ACT  1-;  K I » > L(  )l-.  I C    T  Kl'  1 1  N  I  ( 


l)0() 


The  platinum  needle  used  in  bacterioloj^ic  work  consists  of  a  platinum 
wire,  from  one  millimeter  to  two  millimeters  in  thickness  and  from  five 
centimeters  to  eitjht  centimeters  in  lenjjth.  fused  into  the  end  of  a  ^lasa 
rod  about  five  millimeters  in  thickness  and  from  fourteen  centimeters 
to  eighteen  centimeters  lonij[.     The  rod  is  used  as  a  holder  or  handle  for 


Fig.  436.— Method  of  Holding  Ti-bes.  Cotton,  and  Platinim  Wire  While  Inocclatiso  Solid  Media.— 

{Kixh'i  nifthod,  modififd  jrom  Woodliaui.) 
The  tubes  c  and  d  arc  gra.spcd  as  shown  in  ihr  illuslraiion.     Thi-  cotton  from  d  is  removed,  with  the  thumb  and 

index-finger  ..f  tlu-  rikiht  hand,  and  hel<l  U-twei-n  the  rinx  fini-.r  ,..n.1  littli   tinir.r  ..f  thr  1,-f-  hanH    nt  ^-   thnt 

portion  "I  •  >hiih  was  within  the  tube  is  not  i 

the  same    •  1  is  now  rcmovetl  from  the  tubt- 

as  at  li,  th  'Ions  luing  use<i  .is  dcscribeil  for  t 

quickly  tlr  if  of  a  Bunst-n  burner,  to  remo\i-   .11;. 

glass  rcxl  n  the  ll.ime,  the  nx)  U-inK  healed  to  a  k. 

tube       '^'.  i-  I'll'  111'"-  fr..n.  uhi.h  it  is  .i-siri-.f  • 

pla.. 

the  . 

c  uv 

rcspc-L-i^. 

tube  ino«  1 

beginner  .■ 

during  the  pr..,_r,>,  hi-  t.ihm.  1-  t.iult>\  .in.l  -houl.l  !.■   p  rl,,'..l  I.  i-r    «. .rk.ru  «i"i  I""''    ■  uiiiir.--. 


the  loop.     The  latter  is  variously  curved,  looped,  or  may  be  used  straight. 
as  for  stab  cultures.     (See  Fii?.  43'^> 

Bacteriologic  Examination  of  Water  and  Other  Fluids.'— Sterilize  a 

•  Bacterid  ill  >},'ic  t.-.\aniinati<>ns  of  water  .in<l  ;iir  arr  iiUrn«lmi<l  htTf  as  good 
examples  of  the  practical  application  of  improved  j>latinK  methods,  and  in  order 
that  the  student  may  familiarize  himself  with  the  technic  of  prepanng  plates  and 
securing  pure  growths  therefrom. 


9  lo 


GEXKkAL    LABORATORY    TECHNIC. 


container  in  the  hot-air  sterihzer,  and  collect  the  water  for  examination. 
As  bacteria  multiply  very  ra])idly,  the  examination  should  be  made 
as  soon  as  possible  after  collection;  after  a  few  hours' stand,  particu- 
larly if  the  weather  be  warm,  the  results  obtained  will  be  without  value 
as  to  quantity  of  bacteria. 

Prepare  a  dozen  Petri  dishes  and  a  corresponding  number  of  tubes 
for  plating.     Sterilize  two  burets  so  graduated  as  accurately  to  measure 


Fig.  437. — .\ppARATUs  i-ok  Counting  Colonies. — {Pahcs.) 

PcLri  dishes  are  placed  upon  the  ruled  circle,  and  the  colonies  counted  as  drected  in  the  te.xt.     An  ordinary  slate 

may  lie  ruled  a,s  in  the  above  figure  and  used  for  the  same  purpo.se. 


0.02  to  I  c.c.  Thoroughly  agitate  the  water  in  order  to  diffuse  the 
bacteria  equally  throughout  the  specimen,  and  fill  a  sterile  buret  with 
the  sample  under  examination.  The  test-tubes  of  media,  gelatin,  or 
agar  having  been  fully  liquefied,  are  cooled  to  45°  C.  in  a  water-bath; 
to  each  of  two  of  the  tubes  is  added  0.02  c.c.  of  the  infected  water;  to 
another  pair  of  tubes  0.05  c.c.  of  water  is  added;  to  another,  0.075  c-c.; 
to  another,  o.i  c.c;  to  another,  0.5  c.c;  and  to  another,  i.o  c.c.  The 
tubes  are  thoroughly  shaken,  immediately  poured  in  the  usual  way,  and 


B  AC  T  K  k  I  ( J  1,(  1 1".  IC    T  KC  1 1  N  U" . 


()\  I 


set  aside  for  the  colonies  to  develop.  If  a^ar  has  been  used,  the  plates 
mav  be  incubated.  As  soon  as  the  colonies  develop  they  are  counted. 
A  Petri  dish  countins,'  apparatus  may  be  used,  or  a  slate  upon  which  has 
been  ruled  a  diai,'rani  like  that  shown  in  fij^ure  4M-  AH  the  colonies  in  the 
plate  mav  be  counted  or  the  number  determined  in  one,  two,  or  more 
of  the  wedije-shaped  areas  bounded  by  the  railii  an<l  the  arc,  and  the 
resulting  number  found  for  one  wedse-shai)cd  area  multiplied  by  the 
total  number  of  divisions — sixteen.  The  number  of  colonies  found  in 
the  whole  plate  represents  the  number  of  bacteria  in  the  water  used  for 
the  plate.  For  example:  Several  areas 
counted  jjive  an  average  of  twenty  colonies  a 

to  each  area;  there  are  sixteen  areas:  20  X 
16  =  320.  the  total  number  of  colonies  in 
the  plate;  assumintj  that  the  quantity  of 
water  used  in  makint];  the  plate  was  o.  i  c.c. 
then  one  cubic  centimeter  contains  ten 
times  320  or  3200  bacteria.  If  different 
quantities  of  water  are  used,  the  result,  re- 
duced to  the  unit. — say,  one  cubic  centi- 
meter,— should  be  approximately  the  same, 
one  series  being  a  control  for  the  others. 

In  the  examination  of  sewage  and  of 
other  materials  exceedingly  rich  in  bacteria 
the  large  number  of  organisms  present  in 
even  the  smallest,  most  easily  measured 
(juantity  may  be  too  great  for  satisfactory 
counting.  To  avoid  this  difficulty,  the 
material  to  be  examined  is  diluted  with  an 
equal  quantity  of  sterile  water  ;  should  this 
not  be  sufficient,  further  dilutions  may  be 
made.  In  the  final  calculation  the  dilution 
must  be  taken  into  consideration. 

The  foregoing  test  determines  the  num- 
ber of  bacteria  in  the  sample.  If  it  is  de- 
sired to  find  what  germs  are  present  in  the 
water,  to  make  the  test  complete,  the  col- 
onies are  transplanted  and  studied  as  al- 
readv  directed  when  considering  pure  cul- 
tures. (See  table  illustrating  the  method 
of  recording  principal  characteristics  of  an 
organism.  ]>.  (j^2. ) 

Bacteriologic  Examination  of  Air. — The 
principle  upon  which   the   examination  is 

conducted  is  to  depend  either  upon  sedimentation  upon  a  sterile  surface. 
as  a  Petri  dish  containing  media. — a  very  unsatisfactory  method.— or  to 
secure  the  bacteria  in  a  sterile  filter  bv' aspirating  through  it  a  known 
volume  of  air.  Fig.  438.  with  the  attached  legend,  will  explain  the 
methods  uscl. 

Staining  Bacteria.— Staining  bacteria  greatly  facilitates  the  study  ot 
their  morphologic  characteristics.  For  this  purpose  the  anilin  dyes  are 
almost  exclusivelv  used.  . 

The   anilin   stains   commonly   used   in   the   laboratory    are    fuchsin. 


Fii;.  4,i8. — Hesse's  .Aer'iscdpe. 
This  consists  of  a  hollow  cylinrltT  of  glass, 
a.  sixty  ccnlinu-tcrs  in  IcnRth.  four 
a-ntimelcrs  in  diami-tcr.  pliiKKi*'!  with 
totton  at  l)oth  cmls,  stiTili/cfl,  an>I 
charneil  with  a  layer  of  tulturr,  much 
as  the  Esmarch  plati-s.  The  two  ends 
arc  covered  by  caoutchouc,  one  of  the 
rubt)cr  cai)S  havinK  a  hole  to  admit 
a  ulass  iul)c  by  which  the  tube  J  is 
connectifl  with  the  jjnivity  tiask  h. 
which  is  further  connectctl  to  the  tiask 
c.  The  flask  ft  is  tilled  with  water. 
When  ready  for  us  •.  the  niblter  cap 
and  the  cotton  |)1uk  at  J  are  removed, 
the  flask  ft  Is  tilled  s«i  that  the  con- 
tained water  flows  into  the  tlask  r, 
thereby  aspiratin);  as  muih  air  into 
the  tube  <i  as  water  is  allowed  to  llow 
from  the  upper  to  the  lower  flask. 
The   luU-  1}  is  now   pluKJ{e<1   and   s<t 


aside  for  colonies  to  dcv 

can   lie  counteil   and   tr.w 

in  other  plate  methods.      I 

ijrovcl  tne  foritt^iiii!   '■'■ 

lor  the   tul>c  a  .1 

with   sand    anil    - 

air    thr..u.;Ii    it      • 

sand    < 

plal' 

steril 

th»     villi  111,-     -11,;. ir     ,in 

methods  give  the  best  results. 


Th. 


91  2 


GENERAL    LABORATORY    TECHNIC. 


gentian- violet,  methylene-blue,  and  a  few  others;  they  are  all  applied  in 
practically  the  same  manner.  For  stock,  it  is  best  to  keep  the  dye  as  a 
saturated  alcoholic  solution.  For  staining,  however,  alcoholic  solutions 
are  of  little  value,  as  they  do  not  seem  to  possess  the  penetration  of 
watery  solutions.  The  usual  strength  employed  is  a  one  to  two  per 
cent,  aqueous  solution  of  the  dye;  the  stains  are  unpleasant  to  handle 
and  may  be  prepared  as  follows:  To  a  test-tube — diameter  13  mm. 
to  15  mm. — two-thirds  full  of  distilled  water  add,  drop  by  drop,  a 
saturated  alcoholic  solution  of  the  dye  until  the  water  is  barely  trans- 
parent. This  is  then  poured  into  a  bottle  adapted  with  a  Barnes  dropper. 
(See  cut  of  appropriate  stain  bottle,  p.  46.)  The  solution  so -prepared 
is  about  1.7  per  cent.,  and  may  be  used  whenever  a  one  or  two  per  cent, 
solution  of  the  dye  is  recommended.  The  addition  of  carbolic  acid  to 
aqueous  solutions  of  some  anilin  dyes  seems  to  enhance  their  staining 
power  and  keeping  properties.  For  this  reason,  instead  of  plain  distilled 
water,  as  previously  recommended,  many  workers  use  a  five  per  cent. 


Figs.  439  and  440. — Two  Forms  or  Stewart's  Cover-glass  Forceps. 
Method  of  holding  cover-glass  and  applying  the  stain.  Convenient  for  blood  work,  and  absolutely  necessary  for 
bacteriologic  work:  useful  also  in  sputum  examination,  etc.  The  lower  instrument  shows  a  cover-glass  with 
stain  in  position.  If  the  cover-glass  be  grasped  with  the  film  or  spread  side  toward  the  side  of  the  forceps 
that  has  the  circular  bend  intended  to  fit  the  thumb,  shown  at  A.  there  will  be  no  danger  of  losing  trace  of 
the  side  containing  the  spread,  as  this  side  of  the  forceps  is  practically  always  upward. 


aqueous  solution  of  chemically  pure  carbolic  acid.  It  is  of  the  greatest 
importance  that  the  carbolic  acid  should  be  pure  ;  many  of  the  samples 
of  the  commercial  acid  contain  impurities  that  are  injurious  to  the 
anilin  dyes. 

One  of  the  most  useful  stains  is  the  Koch-Ehrlich  anilin  water  gen- 
tian-violet solution.  This  should  be  freshly  prepared  as,  at  best,  it  keeps 
but  a  few  days.  Take,  in  a  test-tube,  about  twenty  cubic  centimeters 
of  distilled  water;  add  anilin  oil,  drop  by  drop,  shaking  thoroughly 
until  no  more  of  the  anilin  is  dissolved,  the  drops  floating  on  and  in 
the  water,  which  may  become  milk-like  as  the  result  of  emulsification 
of  the  oil;  filter  until  clear:  usually  one  filtration  is  enough,  but  occa- 
sionally two  or  three  are  required. 

Formula  for  stain : 


Saturated  solution  of  anilin  oil  in  distilled  water 

Saturated  alcoholic  solution  of   gentian- violet,  me- 
thyl-violet, or  fuchsin, 

Alcohol 


100  parts. 


HACTliUIOLOC.U"    THl  IINIC. 


913 


As  it  is  not  dcsireil  to  stain  lal^oratory  utensils  any  more  than  can 
be  avoided,  it  has  l)cen  found  that  practically  tlie  same  results  as  those 
secured  bv  measuring  can  be  obtained  by  dro]>ping  the  solutions:  100 
drops  of  the  anilin  water,  21  drops  of  the  alcoholic  solution  of  the  dye, 
and  20  drops  of  alcohol. 

Lojjlcr's  Alkiiliitc  Mclliylciu-hliii'  Solution: 


Saturated  alcoholic  solution  of  nicthylcnc-liluc,  . . 
Aiiueous  solution  of  caustic  i)Otash   (1:10,000),... 


3  parts. 
100 


Zithl's  Carbolfiiclisin. — For  formula,  see  page  49.  This  is  probably 
the  most  useful  bacterial  stain  yet  introduced. 

To  Stain  Bacteria. — Thoroughly  cleanse,  dry,  and  polish  a  cover-glass; 
grasp  it  with  cover-glass  forceps  and  i)ass  through  the  llame  a  number 
of  times  to  burn  off  any  adhering  bacteria  or  other  organic  material ;  avoid 
over-heating,  as  the  cover  may  warp  or  crack.  Si)read  on  this,  with  a 
previously  well  sterilized  platinum  loop  or  needle,  a  thin  film  of  the 
material ;' permit  it  to  dry  without  using  any  artificial  heat.  It  is  then 
"fixed"  by  passing  through  the  flame,  as  follows:  Stand  about  thirty 
centimeters  from  the  flame  and  carry  the  cover-glass  through  a  circle, 
the  diameter  of  which  is  represented  by  the  distance  between  the  flame 


Fig.  441. — Kaltkvkr's  Cover-<;lass_Forceps. 
This  iii.<!trumcnt  may  be  used  exacilv  as  the  forccfis  shown  in  figures  4.19  and  440;   in  addition,  it  may  |)c  used 
as  in  the  illustration.     The  danger  of  forgetting  which  side  of   the  cover  is   coated  is  less  than   with   any 
other  type  of  forceps. 

and  the  worker;  pass  it  through  the  flame  three  times.  Stain  from  two 
to  ten  minutes;  wash  thoroughly  in  water,  dry,  and  mount  with  the 
film  side  downward.  Films  must  be  thoroughly  dried  before  mounting; 
evaporation  of  the  water  accomplishes  the  same  result  as  the  applica- 
tion of  alcohol  in  sections — dehydration;  the  use  of  a  clearing  agent, 
such  as  creasote  or  cedar  oil.  is  usually  unnecessary,  as  the  residual  oil 
present  in  the  balsam  will  clear  satisfactorily,  provided  the  film  is  dry. 
The  presence  of  either  alcohol  or  water  in  the  him  when  mounted  on 
balsam  leads  to  more  or  less  emulsitication  of  the  residual  oil  in  the 
balsam  and  consequent  clouding. 

Temporary  mounts  are  often  made,  thereby  avoiding  the  use  of 
reagents  so  disagreeable  and  sticky  as  damar  or  balsam.  If  the  examina- 
tion is  to  be  made  with  a  dn.-  lens,  the  film  is  turned  over,  with  the 
spread  side  downward,  upon  a  drop  of  water,  the  excess  of  which  is  re- 
moved to  prevent  the  cover-glass  from  floating.  When  an  oil-immersion 
lens  is  to  be  applied,  the  most  satisfactory  temporary  mounts  arc  made 
in  immersion  oil.  The  thoroughly  dried'  Him  receives  in  its  center  a 
59 


914  GENERAL    LABORATORY    TECHXIC. 

droplet  of  cedar  oil,  and  is  then  inverted  on  the  slide;  a  droplet  of  oil 
is  placed  on  its  upper  surface,  and  the  examination  is  proceeded  with 
in  the  usual  manner.  For  method  of  focusing  immersion  objective,  see 
page  51.  Spreads  can  be  made  directly  on  the  slide,  followed  by  fixation, 
staining,  etc.  Such  spreads  may  be  examined  without  a  cover-glass — a 
method  commonly  in  vogue,  but  one  with  which  the  writer  is  not  in 
svmpathy. 

Wcigert's  Method  for  Sections  of  Tissue  Containing  Bacteria. — Place 
sections  for  from  six  to  eighteen  hours  in  a  one  per  cent,  aqueous  solu- 
tion of  any  of  the  basic  anilin  dyes;  after  removal  from  the  stain,  wash 
in  one-half  saturated  solution  of  potassium  carbonate,  then  in  distilled 
water,  next  in  sixty  per  cent,  alcohol,  and  finally  dehydrate  in  absolute 
alcohol;  clear  in  oil  of  cloves,  xylol,  or  cedar  oil,  and  mount  in  xylol  bal- 
sam. Heating  the  stain  or  using  a  stronger  solution  hastens  the  process, 
but  the  results  are  less  satisfactory.  In  case  the  particular  basic  dye 
used  gives  an  unsatisfactory  result  another  should  be  tried,  using  the 
same  formula  and  method. 

Gram's  Method  may  be  used  either  for  cover-glass  films,  prepared  in 
the  usual  way,  or  for  sections.  Stain  in  the  Koch-Ehrlich  solution 
made  with  gentian- violet  (see  p.  912),  from  two  to  five  minutes,  rarely 
twelve  or  twenty-four  hours;  rinse  for  a  moment  in  water,  and  apply 
Gram's  solution. 

Gram's  lodin-iodo-potassic  Solution: 

lodin • I   part. 

Potassium  iodid, 2  parts. 

Distilled  water, 300 

In  films,  after  one  or  two  minutes,  the  iodin  solution  is  washed  off 
with  water,  followed  by  alcohol.  From  time  to  time  the  cover  mav  be 
mounted  in  water  and  examined  with  a  ^-inch  or  |-inch  objective,  and 
as  soon  as  the  excess  of  dye  and  precipitate  has  been  fully  removed,  it 
may  be  dried  and  mounted  in  xylol  balsam. 

As  soon  as  the  section  becomes  dark  brown,  wash  in  sixtv  per  cent, 
alcohol,  dehydrate  in  absolute  alcohol,  continuing  the  latter  as  long  as 
any  perceptible  amount  of  color  is  discharged,  clear  in  oil  of  cloves  or 
cedar  oil  in  which  a  small  amount  of  color  may  be  discharged,  pass 
through  one  or  two  changes  of  xylol,  and  mount  in  xylol  balsam.  After 
washing  in  sixty  per  cent,  alcohol,  sections  may  be  contrast  stained  with 
carmin  or  hematoxylin,  or  with  a  one  per  cent,  aqueous  solution  of 
vesuvin  or  Bismarck  brown. 

Neisser's  method  of  spore  staining  consists  in  preparing  the  film  in 
the  usual  manner,  floating  it  upon  the  Koch-Ehrlich  solution  (made  with 
gentian-violet)  in  a  watch-glass,  and  heating  to  near  the  boiling-point 
for  an  hour.  The  film  is  next  washed  in  water  and  decolorized  bv  a 
solution  composed  of  twenty-five  parts  of  hydrochloric  acid  and  seventv- 
five  parts  alcohol.  This  removes  the  stain  from  the  bacilli,  but  if  not 
allowed  to  act  too  long,  leaves  the  spores  stained.  The  preparation  is 
next  stained  with  methylene-blue,  washed  in  water,  dried,  and  mounted. 

Flagella   Staining.^ — Loflaer's  method   requires   two   fluids,    the  first 

'Sec  also  Johnston  and  Mack,  "Amer.  Med.,"  May  7,  1904. 


HACTIvklOl.oGIC    TI'CIIMC.  QI5 

lioirii,'    a     monlaiU.     the    set-ond     the    stain.       I-'irsi     sohition    consists 
of: 

A(iuciius  solutiuti  of  tannin   (20  jjin-  tannin   to  So  c.c. 

water), lo  c.c 

Aqueous  solution  of  ferrous  suljihate,  saturated  in  the 


eoM. 
Saturated  aleoholic  solution  of  fuchsin, 


5  c.c. 
I  c.c. 


The  coloring,'  solution  is  composed  of  saturated  solution  of  fuchsin  in 
anilin  water,  to  which  are  added  a  few  drojxs  of  caustic  soda  (i  :  looo) 
until  opalescence  commences.  The  mordant  is  a])plicd  to  the  cover- 
glass  film,  heatins.!;  slowly  over  the  flame  for  one  minute.  It  is  not  neces- 
sary for  the  liquid  to  boil.  Wash  in  distilled  water  and  then  in  alcohol. 
Stain  by  placinj^  on  the  Him  a  drop  of  the  alkaline  staining  .solution, 
heating  again  gently  for  one  minute;  wash  in  distillefl  water,  drv  in  air, 
and  mount. 

Different  species  of  bacteria  require  an  acid  or  alkaline  reaction  to 
the  mordant,  and  for  this  purpose  two  solutions  are  necessary:  (i) 
Caustic  soda,  one  per  cent,  aqueous;  (2)  an  aciueous  dilution  of  sulphuric 
acid,  of  which  one  cubic  centimeter  just  neutralizes  one  cubic  centi- 
meter of  the  alkaline  solution.  For  spirillum  of  cholera,  one-half  to  one 
drop  of  the  acid  solution  to  sixteen  cubic  centimeters  of  the  mordant; 
for  Bacillus  typhosus,  two  cubic  centimeters  of  the  alkali  to  sixteen  cubic 
centimeters  of  the  mordant,  and  so  on;  the  number  of  drops  of  either 
solution  can  be  determined  only  by  experiment  upon  the  organism  in 
([uestion.  The  Bacillus  pyocyaneus  and  many  varieties  of  the  spirillum 
rerjuire  an  acid  reaction,  while  the  Bacillus  typhosus,  Bacillus  subtilis, 
bacillus  of  malignant  edema,  and  bacillus  of  symptomatic  anthrax 
require  an  alkaline  reaction. 

Pitfield  devised  the  following  stain  for  flagclla,  using  but  one  solution 
for  mordant  and  stain : 

(A)  Saturated  aqueous  solution  of  alum...  10  c.c. 
Saturated  alcoholic  .solution  of  j,'cntian-viukt  i   c.c. 

(B)  Tannic  acid i   gm. 

Distilled  water, 10  c.c. 

These  are  made  separately,  filtered  and  mixed.  The  resulting  mixture — 
stain  and  mordant  combined — is  aj)plied  and  heated  gently  almost  to 
boiling-point,  washed  in  water,  dried,  and  mounted. 

McCrorie's  flagella  stain  is  a  single  fluid  having  the  following  com- 
position: 

Xii^ht  blue,  saturated  alcoholic  solution,...  10  c.c. 

Tannic  acid,    10  per  cent.  aqueou.s  solution.  10  c.c. 

Alum,    10  per  cent,  aqueous  solution 10  c.c. 

Spreads  are  made  from  cultures  eighteen  to  twenty-four  hours  old ; 
the  rtlm  is<lried  and  fixed  as  usual.  The  stain  is  applied  for  two  minutes 
cold  and  then  warmed  until  a  faint  haze  of  steam  is  given  off.  Wash 
thoroughly  in  water,  dry,  and  mount  in  balsam.  Of  the  many  stains 
for  flagella  that  have  been  advised,  this  seems  to  yield  the  best  results. 

Duckwall's  Flagella  Stain':    Using  gentle  heat  dissolve  2  gm.  of  tan- 

'  "New  York  Med.  jour.,"  June  24,  1005,  p.  1253. 


9l6  GENERAL    LABORATORY    TECHNIC. 

nil!  in  15  c.c.  of  water;  add  (i)  5  c.c.  of  an  aqueous  solution  of  ferrous 
sulphate  saturated  in  the  cold,  (2)  i  c.c.  of  a  saturated  alcoholic  solution 
of  basic  fuchsin;  and  0.5  c.  c.  to  i  c.c.  of  a  one  per  cent,  aqueous  solution  of 
sodium  hydroxid;  filter  through  two  papers.  The  spreads  are  prepared 
by  mixing  a  drop  of  water  of  condensation  from  a  twenty-four  hour 
old  agar  culture  with  a  drop  of  sterile  water  on  a  perfectly  clean  cover- 
glass,  which  is  then  tilted  from  side  to  side,  to  distribute  the  bacteria; 
dr\'  under  a  bell-jar.  Flood  the  dried  film  with  the  above  solution  and 
heat  over  flame  until  vapor  arises,  continuing  to  heat  for  one  or  two 
minutes.  Add  a  few  drops  of  95  per  cent,  alcohol,  rock  the  cover,  and 
rapidly  flush  with  water.  After  washing  drain  the  cover,  touching  its 
edge  to  bibulous  paper,  and  apply  stain  consisting  of  fuchsin  i  gm., 
absolute  alcohol  13  c.c,  of  a  5  per  cent,  aqueous  solution  of  carbolic  acid 
100  c.c;  heat  gently  for  one  or  two  minutes  and  almost  boil  for  thirty 
seconds;  add  a  few  drops  of  95  per  cent,  alcohol,  wash  with  water,  and 
dry  under  a  bell-jar.  Both  mordant  and  stain  give  better  results  when 
not  over  twenty-four  hours  old. 

Buerger^  recommends  the  following  method  for  staining  capsules: 
Sputum,  pus,  or  other  albuminous  fluid  containing  the  organism  is 
spread  on  a  perfectly  clean  cover-glass;  as  soon  as  the  edges  begin  to 
dry,  the  film  is  covered  by  Zenker's  solution  (p.  35),  omitting  the  acetic 
acid.  Warm  over  the  flame  about  three  seconds,  rapidly  wash  in  water 
followed  by  alcohol,  tincture  of  iodin,  and  finally  thoroughly  wash  with 
alcohol  and  dry  in  the  air.  It  is  then  stained  in  a  mixture  consisting 
of  anilin  oil  10  c.c,  water  100  c.c,  thoroughly  mixed  and  filtered,  and 
5  c.c.  of  a  saturated  alcoholic  solution  of  gentian-violet.  The  stain 
should  act  for  from  two  to  five  seconds,  after  which  time  it  is  washed  off 
with  a  two  per  cent,  aqueous  solution  of  salt,  in  which  it  is  mounted, 
and  ringed  with  vaselin.  The  success  of  the  stain  demands  the  presence 
of  a  proteid,  usually  supplied  by  exudates,  but  when  stains  are  to  be  made 
from  cultures  it  must  be  artificially  added.  A  drop  of  blood-serum 
diluted  with  an  equal  quantity  of  salt  solution,  or  ascitic  or  pleural  fluid, 
is  placed  on  a  cover;  the  bacteria  to  be  stained  are  mixed  yvith  this 
diluted  serum  and  spread  evenly  over  the  surface;  from  this  point  the 
technic  is  the  same  as  that  given  for  sputum  and  pus. 

Hiss^  recommends  staining  in  a  concentrated  solution  of  gentian- 
violet  heated  until  steam  arises;  wash  in  twenty  per  cent,  aqueous 
solution  of  copper  sulphate;   blot  on  filter,  dry  and  mount  in  balsam. 

Microscopic  Examination  of  Stained  and  Unstained  Mounts. — In 
tissues  stained  by  any  of  the  methods  given,  the  location,  under  a  low 
power, — l^-inch  objective, — of  bacteria  can  often  be  inferred  by  ag- 
minated  areas  of  the  dye  known  to  stain  such  organisms.  Having 
located  such  an  area,  a  higher  power  may  be  used.  Always  begin  the 
examination  with  a  low  power. 

(For  description  of  microscope  and  method  of  using  same,  see  pp. 
SI  to  52.) 

Gas  formation  may  be  investigated  in  connection  with  a  study  of 
yeasts.  Thus,  if  a  saccharometer  charged  with  a  sterile  culture  fluid 
containing  glucose  be  inoculated  with  the  Saccharomyces  cerevisiae, 
gas  collects  in  the  measuring-tube,  showing  its  production  by  the  growth 

^  "Medical  News,"  December  10,  1904. 

'  "Jour,  of  Experimental  Medicine,"  vol.  vi,  p.  335. 


n.\cTi;RioLf)c,ic  tkchnmc. 


917 


of  the  yeast.  In  addition  to  the  evolved  j^as,  it  can  he  shown  that  the 
tluid  contains  other  substances;  simultaneously  with  the  gas  production 
alcohol  is  elaborated.     The  equation  is  written  as  follows: 

Glucose  (CgHuOg)  =  Alcohol  (2C,H,0)  +  Carbon  Dioxid  (2CO,). 

The  study  of  gas  formation  is  conducted  for  other  organisms  after 
the  same  method  as  described  for  the  yeasts;  while  saccharine  fluids 
are  mostly  used  for  this  study,  other  media  have  also  been  found  avail- 
iible. 

Gelatin  or  agar  sJuikc  ciiltiin's  are  sometimes  used  to  detect  gas  for- 


FiG.  442. — Novy's  .'Vpparatls  for  /Vnaerobic  Cvl- 
TivATioN  OF  Plates  and  Test-tubes. 

The  apparatus  consists  of  the  following  parts:  A,  the 
l)a.so,  a  solid  glass  cylinder  ha\-ing  a  capacity  of 
abr)ut  one  liter  and  Rround  at  its  upper  edge  with 
a  tlange  to  m.ake  an  air-tight  joint  with  B,  the 
dome,  the  two  being  clamped  together  hy  the  vise- 
like  clamps,  D.  I),  the  joint  U-ing  more  perfectly 
assured  by  rubber  bands.  The  lop  of  the  dome, 
B,  arches  into  a  neck  like  that  of  a  bottle,  and  is 
closed  by  C.  which  is  an  ordin.iry  ground-glass 
stopper  grouml  into  the  mouth  of  the  neck,  to 
the  dome  B.  Through  the  side  of  the  glass  stop- 
per. C.  arc  two  openings,  so  arranged  that  when 
C  is  turned  as  shown  in  the  cut  the  openings  permit 
gas  to  fxiss  into  the  interior  of  the  ap|Kiratus 
through  either  of  the  tubulatures  shown  at  the  side 
of  the  neck.  On  the  inside  of  the  stopper  an  L- 
shapcd  tube  is  fusotj.  so  that  any  gas  carried  into 
the  apfAiratus  through  that  tubuLiture  parses  below 
the  level  of  the  opprjsite  tubulature. 


Fig.  443. — Sternberg's  .^NAEROBtc  Culture  Tube. 

The  tube  is  an  ordinary  culture  tube  of  rather  large 
size.  The  culture  medium,  c  is  inoculated,  the 
cotton  plug,  d,  while  at  the  top  of  the  tulie,  is  ciit 
even  with  the  glass  and  held  in  the  flame  until 
thoroughly  browned,  fully  to  steriliM  it,  and  is 
then  pushed  down  into  the  tube  with  a  sterile 
glass  rod.  A  cork,  f ,  with  two  perforations,  through 
which  pass  the  L-shajxKi  tubes,  a.  is  fitte<l  to  the 
mouth  of  the  test-tube  and  scale<l  with  wa.x  at  b. 
Hydrogen  gas  is  now  jxissed  through  the  apparatu.s 
for  an  hour  or  so,  depending  utxjn  the  size  of  the 
tube,  until  all  the  air  is  displaced;  the  entrance  and 
e.Tit  tubes  are  then  sealed  at  j'  a'  by  fusing  the 
gl.x'^s.  The  ailvantage  of  this  simple  method  is 
that  any  tube  can  be  used  with  any  of  ihc  common 
media  in  use  in  the  Lil>oralory. 


mation.  Either  medium  is  liquetied,  cooled  to  below  50°  C,  and  in- 
oculated while  liquid;  it  is  then  thoroughly  agitated  and  allowed  to 
solidifv.  The  growth  of  organisms  producing  gas  will  be  evident  by  the 
appearance  of  small  bul)bles  throughout  the  medium.  The  test  is,  at  times 
facilitated  by  using  a  medium  containing  glucose,  in  which  case  the 
reaction  may  be  identical  with  that  previously  described;  in  many 
cases  it  is,  however,  a  much  more  complex  problem. 

Anaerobic  Cultures. — Novy's  Apparatus  (Fig.  442). — Petri  plates, 
Esmarch  plates,  or  culture  tubes  are  placed  inside;  the  dome,  B,  is  put 
in  position  and  secured  by  the  vise-like  clamps,  D,  D;   the  glass  stopper 


9i8 


GENERAL    LABORATORY    TECHNIC. 


is  turned  as  shown  in 
extension  downward 


the  cut.  The  tubulature  not  having  the  L-shaped 
is  connected  with  the  hydrogen  generator,  and  a 
constant  stream  of  gas  is  carried  through  the 
apparatus  for  some  hours.  As  soon  as  the  air  is 
displaced,  the  stopper,  C,  is  rotated  one-fourth 
of  a  turn,  thus  closing  the  connection  between  the 
tubulatures  on  the  side  of  the  neck  and  the  in- 
side of  the  apparatus.  If  carbon  dioxid  is  used 
instead  of  hydrogen,  it  is  admitted  through  the 
tubulature  that  communicates  with  the  inside 
through  the  L-shaped  piece.  The  author  has 
fancied  that  the  exclusion  of  air,  when  using 
hydrogen,  was  facilitated  by  attaching  to  the 
L-shaped  piece  a  soft-rubber  tube  extending  to 
the  bottom  of  the  apparatus;  as  air  is  much 
heavier  than  hydrogen,  this  device  causes  the 
gas  admitted  through  the  opposite  tubulature  to 
displace  the  air  more  rapidly.  The  method  de- 
vised by  Sternberg  is  explained  in  the  legend 
beneath  figure  443.  A  more  recent  appliance 
for  excluding  the  air  without  the  use  of  hydrogen 
or  carbon  dioxid  is  that  devised  by  Wright.  Its 
form  and  method  of  application  are  indicated 
in  figure  444.  Hamilton  cultivates  anaerobes  in 
glucose-peptone-bouillon  upon  the  surface  of 
which  he  maintains  a  layer  of  olive  oil  1.5  cm. 
deep;  inoculations  and  removals  are  made  with 
a  sterile  pipet  thrust  through  the  oil.  The  ad- 
vantages of  this  method  are  its  simplicity  and 
the  fact  that  prepared  sterile  media,  always  ready 
for  anaerobic  inoculation,  can  constantly  be  kept 
on  hand.^ 

Hanging-drop  Cultures  for  the  Demonstration 
of  Motility. — If  a  drop  of  liquid  culture  be  placed 
on  a  slide  and  covered  in  the  usual  manner,  exam- 
ination with  a  high  power  will  usually  demon- 
strate the  motility  of  an  organism.  This  crude 
method  is  not  accurate,  as  heat  currents  always 
occur  in  fluids  under  a  cover-glass,  and  may 
mislead  the  observer.  For  demonstrating  mo- 
tility the  drop-culture  slide  is  used.  This 
consists  of  a  thick  slide  of  the  same  dimen- 
sions as  the  ordinary  microscope  slide,  with  a 
concavity  ground  in  its  center.  A  clean  cover- 
glass  is  grasped  in  the  forceps  and  is  passed  ■ 
through  the  gas-flame  to  sterilize  it.  The 
concave  slide  is  prepared  in  the  same  way, 
allowed  to  cool,  and  around  the  concavity  is 
painted   a   thin   line   of    any   nonvolatile    oil — 

*  For  full  review  of  newer  anaerobic  methods  see  Stuler,  "  Centralbl.  f.  Bakt. ," 
Oct.  17,  1904,  p.  298;  also  "Jour,  of  Applied  Microscopy', "  March,  April,  and 
May,  1902. 


Fig.  444. — Wright's  Method 
FOR  .Anaerobic  Cultiva- 
tion IN  Liquid  Media. 

A.  Spindle-shaped  glass  tube,  at 
the  lower  end  of  which  is  at- 
tached a  short  piece  of  rub- 
ber tubing  (lower  b).  c.  Rub- 
ber tubing  connecting  upper 
end  of  a  with  lower  end  of  D. 
D.  Glass  tube  stoppered  with 
cotton  at  upper  b,  and  con- 
tinued upward  by  the  rubber 
tube  E.  For  use,  the  appar- 
atus is  prepared  as  shown  on 
the  left,  sterilized  by  steam, 
and  may  be  kept  in  stock. 
Before  inoculation  the  me- 
dium in  the  tube  is  boiled 
to  drive  off  absorbed  gas, 
cooled,  and  inoculated.  Suc- 
tion is  applied  to  the  rubber 
tube  E,  draw-ng  the  contained 
fluid  upward  to  point  indi- 
cated in  drawing  on  the  right; 
the  tube  is  then  thrust  down- 
ward, kinking  the  rubber 
tube  r,  and  in  a  similar  man- 
ner closing  the  rubber  tube  at 
the  lower  end  of  A.  It  is 
claimed  that  this  apparatus 
affords  a  ready  method  of 
securing,  at  the  same  time, 
both  aerobic  and  anaerobic 
cultures  in  the  one  tube. 


BACTERK)LOGIC    TECHNIC.  QIQ 

ordinary  sperm  oil.  vasclin.  or,  wlit'ii  the  slide  is  to  be  incubated,  parafiin 
or  oleum  theobroma  litiuetied  by  j,'entle  heat.  A  droplet  of  the  culture 
in  bouillon  or  Dunham's  solution  is  i)laced  in  the  center  of  the  cover- 
U'lass,  which  is  then  inverted  over  the  hollow  slide,  care  beinj(  taken  that 
the  droplet  is  very  small, — not  larger  than  a  small  pinhead,  so  that  it 
will  not  sway  from  side  to  side, — and  that  it  does  not  come  in  contact 
with  the  slide  at  any  point.  With  the  stage  of  the  microscope  per- 
fectly horizontal,  the  droplet  is  carefully  focused.  The  moving  bacteria 
can  be  easilv  seen,  provided  the  illumination  is  satisfactory;  the  iris 
diaphragm  should  be  closed  to  admit  but  little  light,  otherwise  the  field 
will  be  so  flooded  with  light  that  the  small,  colorless  bodies — the  bacteria 
— may  escape  detection.  It  is  often  advisable  to  center  the  drop  with  a 
low  power — say,  a  A-inch  or  J-inch  objective — before  attempting  to 
focus  with  a  high  power.  If  the  organism  is  growing  on  a  solid  medium, 
a  small  part  of  the  culture  is  mixed  with  the  bouillon  or  Dunham's 
solution  on  a  sterile  cover,  and  the  hanging  drop  ])repared  from  the 
mixture. 

The  "hanging-drop  culture" — as  such  the  foregoing  is  known — may 
be  incubated  and  kept  under  observation  for  a  long  time  if  care  is  used 
to  avoid  infection  during  its  preparation  and  to  exclude  bacteria  by  a 
perfect  oil  seal.  By  incubating  hanging  drops,  bacteria  can  be  seen 
dividing,  yeasts  watched  while  forming  and  throwing  ofi  buds,  and  other 
observations  made.     (See  Widal's  test,  p.  929.) 


r    --         .     -     »  1 

Fig.  445. — Drop-cui.tlre  Sliuk. 
(7S  X  as  mm.,  of  polished  plate  glass,  with  a  ca\ity  18  mm.  in  diameter.) 

During  the  growth  of  many  bacteria,  bodies  are  elaborated  that 
change  the  reaction  of  the  culture  medium.  This  test  is  applied  by 
adding  an  indicator  to  the  tiuid,  or  other  medium,  and  observing  whether 
the  color  of  the  indicator  changes.  The  two  indicators  most  commonly 
used  are  litmus  and  phenolphthalein;  the  former  is  kept  in  stock  as  a 
tincture,  and  the  latter  as  a  o.i  per  cent,  solution  of  the  salt  in  hfty  per 
cent,  alcohol.  To  apply  the  test,  a  number  of  tubes  of  culture  media — 
milk,  bouillon,  or.  what  is  best  of  all,  Dunham's  solution — are  prepared; 
although  much  less  suitable,  solid  culture  media,  such  as  gelatin,  agar, 
or  potato,  may  be  used.  In  bulk,  some  of  the  medium — sufficient  to 
fill  several  test-tubes  of  the  size  intended  for  use — has  added  to  it  enough 
of  the  indicator  to  show,  faintly  but  clearly,  the  reaction;  one  part  of 
the  medium  should  be  but  faintly  acid,  ver\'  dilute  acetic  acid  being 
used  to  acidify;  another  portion  should  be  rendered  faintly  alkaline 
bv  the  use  of  one  per  cent,  caustic  potash,  while  a  third  is  neutral. 
With  great  care  sterile  media  may  be  sensitized  without  subsequent 
sterilization;  as  a  rule,  however,  after  sensitizing  it  is  necessary  to  re- 
sterilize.  The  same  fjuantity  should  be  in  each  tube.  A  number  of 
tubes  belonging  to  each  series  are  inoculated  with  the  germ  in  question, 
and  several  are  left  as  test  or  control  reserves.  In  the  course  of  a  few 
days,  often  in  less  than  twenty-four  hours,  it  will  be  observed  that  the 
reaction  of  the  two  series  is  changing.  If  the  germ  produces  an  alkaline 
reaction,  the  neutral  series  evinces  the  change  first,  followed  by  the  acid 


920  GENERAL    LABORATORY    TECHXIC. 

series  becoming  less  markedly  acid  and,  in  some  instances,  eventually 
manifesting  a  clearly  defined  alkaline  reaction.  The  alkaline  series 
may  show  a  slight  intensification  of  the  alkaline  reaction  or  may  not 
change  at  all.  If  the  organism  produces  an  acid,  the  reaction  just  given 
will  be  reversed.     In  either  case  the  control  tubes  remain  unchanged. 

Rosolic  acid  is  also  used  as  an  indicator;  the  stock  solution  is  prepared 
by  adding  0.5  gm.  of  the  acid  to  100  c.c.  of  eighty  per  cent,  alcohol. 
Its  use  is  the  same  as  the  foregoing;  it  pales  when  acid,  intensifies  its 
rose-color  when  alkaline. 

Indol. — Among  the  chemic  tests  applied  for  the  identification  of 
bacteria  is  that  for  indol.  Several  tubes  are  charged  with  seven  cubic 
centimeters  of  Dunham's  solution,  sterilized,  and  three  or  four  inoculated 
with  the  germ  under  investigation,  and  twice  the  number  reserved  for 
controls.  After  twenty-four  hours  add  to  one  of  the  controls  ten  drops 
of  chemically  pure  sulphuric  acid,  and  to  another  one  cubic  centimeter 
of  a  sodium  nitrite  solution,  freshly  prepared  by  dissolving  one  gram  of 
chemically  pure  sodium  nitrite  in  10,000  c.c.  of  ammonia-free  water. 
To  the  second  tube  also  add  ten  drops  of  sulphuric  acid.  Both  tubes 
should  be  watched  for  fifteen  or  twenty  minutes;  no  color  should  develop, 
as  they  contained  no  indol.  To  one  of  the  inoculated  tubes  add  the  sul- 
phuric acid,  and  if  in  from  ten  to  twenty  minutes  no  reaction  occurs, 
add  the  sodium  nitrite  solution,  as  previously  directed;  if  indol  be 
present,  a  distinct  rose-color  appears.  Occasionally  the  rose-color  may 
appear  without  the  addition  of  the  sodium  nitrite,  in  which  case  the 
organism  has  produced  not  only  indol,  but  also  a  reducing  agent,  com- 
monly a  salt  of  nitrous  acid. 

Thermic  Disinfection. — Each  organism  thrives  best  at  a  certain  tem- 
perature, known  as  its  optimum  temperature.  Variations  above  or  below 
the  most  favorable  degree  of  heat  influence  the  growth  of  the  germ  in 
question.  The  lowest  temperature  at  which  growth  takes  place  is 
called  the  minimum  temperature;  the  highest,  the  viaximum  temperature. 
The  three  thermal  points  are  rarely  the  same  for  any  two  organisms,  and 
hence  constitute  important  tests  in  the  identification  of  a  germ  under 
investigation.  The  thermal  death-point  is  that  degree  of  heat  destroying 
the  life  of  a  germ;  a  knowledge  of  the  point  at  which  the  organism  is 
destroyed  also  aids  in  the  differentiation  of  bacteria.  The  thermal 
death-point  is  not  constant  for  the  same  microbe  under  all  conditions, 
varying,  in  some  cases,  with  the  age  of  the  organism,  the  presence  or 
absence  of  moisture,  etc.  Again,  moist  heat  is  usually  destructive  to 
bacteria  at  a  lower  temperature  than  dry  heat;  and  moist  heat  under 
pressure  (superheated  steam)  more  penetrating  and  more  rapidly  fatal 
than  dry  heat  at  the  same  temperature. 

In  order  to  determine  the  thermal  death-point  of  a  given  organism 
all  the  foregoing  factors  must  be  borne  in  mind,  as  well  as  the  length  of 
time  of  exposure.  The  latter  also  varies  with  the  conditions  under 
which  the  test  is  made.  A  temperature  of  70°  C,  moist  or  dry,  and 
continued  for  one  or  two  hours,  may  be,  to  a  given  organism,  as  certainly 
fatal  as  100°  C.  with  an  exposure  of  ten  minutes.  The  thermal  death- 
point  in  the  presence  of  moist  heat  is  commonly  determined  by  expo- 
sure of  bouillon  cultures,  infected  material,  or  dried  threads — prepared 
as  described  under  Chemic  Disinfection  (see  below) — to  different  tem- 
peratures and  for  different  lengths  of  time  in  the  steam  sterilizer  (Fig. 


BACTHRKJLoGIC    TECUNIC.  g2I 

431,  p.  905)  or  in  the  autoclave  (Fig.  432,  p.  906).  In  making  the  test 
with  dry  heat  the  hot-air  steriUzer  (Fig.  428,  p,  903)  is  used,  and  pre- 
viously dried  infected  materials,  especially  dricii  threads,  make  the  best 
test-objects.  After  exposing  the  infected  material  to  heat,  inoculations 
are  made  upon  suitable  culture  media;  the  tubes  are  incubated  and 
kept  under  observation  a  sufficient  time  for  the  development  of  any  un- 
destroyed  germs.  The  thermal  death-point  of  an  organism  may  be 
determined  even  before  its  successful  cultivation.  Such  an  experiment 
is  permissible  only  when  we  can  not  successfully  cultivate  the  germ. 
In  order  to  make  the  test  we  must  be  able  to  infect  an  animal.  Material 
that  is  known  to  contain  the  organism  in  question  is  subjected  to  heat, 
and  after  definite  exposures,  is  inoculated  into  susceptible  animals. 
If  disinfection  has  been  complete,  the  inoculated  animals  escape.  A 
source  of  error  lies  in  the  well-known  fact  that  the  pathogenicity  of  an 
organism  may  be  lowered  without  of  necessity  destroying  its  viability; 
if,  however,  the  experiment  has  rendered  the  germ  no  longer  capable  of 
inducing  disease,  its  infectivity  is  removed,  and  therefore  disinfection, 
in  the  theoretic  sense,  has  been  secured. 

For  determining  the  thermal  death-point  a  number  of  factors  must  be 
considered,  otherwise  results  can  not  be  uniform.  The  following  general 
plan  is  recommended  by  Dalton  and  Eyre :  ^  Length  of  exposure,  ten  min- 
utes; the  emulsion  used  for  the  test  to  consist  of  3  c.c.  of  sterilized  nor- 
mal salt  solution  or  water  to  which  has  been  added  3  mgm.  of  the  culture 
from  an  optimum  cultivation,  the  mixture  exposed  in  a  test-tube  1.5 
cm.  in  diameter  with  wall  i  mm.  thick.  The  exposure  should  be  made 
in  a  thermoregulated  water-bath.  The  thermal  death-point  to  be  the 
lowest  temperature  that  will  kill  all  the  organisms  exposed  to  it  in  the 
time  limit  of  ten  minutes. 

Theoretically,  there  should  be  two  death-points — a  maximum  and  a 
minimum;  but  experience  has  satisfactorily  proved  that  there  is  at 
present  available  no  temperature  sufficiently  low  to  act  as  a  disinfectant 
upon  which  it  is  possible  to  rely.  Reduction  below  zero  commonly 
determines  only  a  stage  of  inactivity  that  ends  with  return  of  the 
organism  to  conditions  again  compatible  with  growth. 

Chemic  Disinfection. — In  addition  to  the  influence  of  thermic  changes 
on  bacteria,  it  is  necessary  to  study  the  effect  of  disinfectants  l:)elonging 
to  the  chemic  group.  The  relation  of  other  physical  agents  than  heat 
may  also  be  studied:  c.  g.,  drying,  light,  and  electricity.  In  studying 
disinfectants,  solutions  are  to  be  used  almost  exclusively;  insoluble  dis- 
infectants are  of  more  than  doubtful  value.  Again,  a  culture  medium 
must  be  used  that  does  not  alter  the  chemical  in  question.  Thus, 
if,  in  the  study  of  corrosive  sublimate,  a  culture  medium  rich  in  albumin 
or  strongly  alkaline  be  used,  the  mercurial  is  instantly  decomposed 
when  it  comes  in  contact  with  the  culture  medium,  and,  it  may  be,  be- 
fore it  has  had  time  to  act  upon  the  bacteria.  Having  found  the  de- 
sired culture  medium,  the  next  point  to  determine  is  the  exact  point  at 
which  the  body  under  investigation  ceases  to  be  antiseptic:  that  is, 
inhibits  the  growth  without  of  necessity  destroying  the  life  of  the  bac- 
teria. For  this  purpose  a  series  of  tubes  of  culture  media  are  prepared 
containing  the  antiseptic  in  var^'ing  (juantities.  These  are  best  pre- 
pared, if  possible,  by  taking  50  or  100  tubes  of  the  medium  it  is  desired 
'  "  Jour,  of  Hygiene."  April,  1904,  p    158. 


922 


GEXERAL    LABORATORY    TECHXIC. 


OLQ 


to  use,  sterilized  in  the  usual  way:  To  ten  of  these  enough  of  the  agent 
is  added  to  make  the  strength  ten  per  cent.;  to  another  ten,  enough  to 
make  the  strength  live  per  cent.;  to  another  ten,  four  per  cent.;  and  so 
on,  covering  various  percentages. 

All  these  tubes  are  inoculated  with  the  germ  that  it  is  proposed  to  use 
for  the  test.  A  series  will  be  found  in  which  dilution  is  so  great  that  the 
agent  no  longer  perceptibly  influences  growth  of  the  germ;  another 
series  contains  a  sufficient  amount  of  the  germicide  to  inhibit  repro- 
duction but  not  destroy  vitality ;  in  the  third  group  of  tubes  the  microbe 
is  killed.  The  strength  at  which  disinfection — that  is,  destruction  of 
reproductive  power — occurs  may  be  approximately  inferred  by  diluting 
with  the  same  sterile  culture  medium  the  tubes  in  which  no  growth  has 
evinced  itself,  so  that  the  proportion  of  the  disinfectant  in  the  dilution 

shall  be  less  than  that  already  found 
not  to  inhibit  growth.  After  this  dilu- 
tion the  bacteria  that  have  not  been 
destroyed  develop,  showing  in  what 
strength  disinfection  has  been  com- 
plete. This  has,  however,  taken  so 
much  time — probably  days — that 
doubt  may  still  exist  as  to  the  rapidity 
with  which  the  agent  in  question  acts ; 
and  as  the  time  required  by  a  given 
solution  to  destroy  viability  is  impor- 
tant, the  rapidity  of  action  and  the 
necessary  strength  for  practical  dis- 
infection must  be  determined.  For 
this  purpose  a  number  of  methods 
have  been  suggested,  all  of  which  are 
open  to  certain  sources  of  error. 

To  a  number  of  cultures  in  a  liquid 
medium  the  agent  in  question  is 
added,  so  as  to  make  the  percentage 
such  as  has  been  found  in  the  previous 
test  to  be  destructive ;  the  added  solu- 
tion is  thoroughly  mixed  with  the  cul- 
ture, from  which  inoculations  are 
made  at  intervals  of  minutes  for  as  long  as  an  hour.  The  removal  must 
be  made  into  tubes  containing  sufficient  of  the  medium  to  dilute  the 
material  carried  over  beyond  the  strength  already  shown  to  have  an 
inhibitory  action,  so  that  any  undestroyed  bacteria  may  be  free  to 
develop. 

The  source  of  error  by  this  method  lies  in  the  clumping  of  the  germs 
in  the  original  tube;  if  grouped  in  clumps,  the  agent  may  not  have 
penetrated  the  clumps.  Penetration  is  a  most  important  point,  for 
without  this  power  a  disinfectant  is  of  little  practical  value;  as,  in  all 
purposes  for  which  germicides  are  used,  a  certain  degree  of  penetration 
is  necessary,  this  apparent  objection  is  not  without  its  good  side.  To 
get  rid  of  "the  clumps,  cultures  are  made  in  a  medium  containing  fine 
quartz  sand;  this  is  shaken  up  in  the  culture  and  the  culture  filtered 
through  glass  wool  and  the  filtrate  used  for  the  test.  Tubes  containing 
the  sand  may  have  mixed  with  them  growing  cultures  containing  no  sand. 


Fig.  446. — Small  Incubator  SuFFiaENixy 
Lakge  for  IxDmDU.AL  Work. 


BACTERIOLOC.IC    T  ICC  II  N  I  C.  923 

Again,  threads  of  silk  from  two  (.iMitiinctcrs  to  six  centimeters  in  length 
may  be  placed  in  tubes  of  li(|uid  eulture  media,  the  tubes  sterilized  as 
usual,  and,  when  sterile,  infected  with  the  germ  that  it  is  intended  to 
use  for  the  test.  When  the  culture  is  well  grown,  it  is  shaken,  the 
threads  are  withdrawn,  and  may  be  used  as  test  bodies  to  disinfect;  they 
mav  be  first  tlricd  in  sterile  dishes  or  they  may  be  used  moist,  A 
source  of  error  lies  in  the  (juantity  of  the  disinfectant  that  the  thread 
mav  convey  into  the  tube  into  which  it  is  transplanted  after  treatment 
with  the  disinfectant.  In  some  cases  this  may  be  partly  avoided  by 
washing  the  thread  in  sterile  water  or  in  some  solution,  or  by  exposing 
it  to  a  vapor,  which,  by  chemic  action,  converts  the  disinfectant  into  an 
insoluble  or  inactive  compound.  Thus,  threads  which  have  been  in 
corrosive  sublimate  solutions  may  be  exposed  to  ammonium  sulphirl 
vapor,  the  solution  converting  the  mercurial  into  an  insoluble  and 
inactive  sulpliid. 

It  will  be  noted  that  one  of  the  essential  elements  is  to  make  the 
transplantation,  after  treating  the  thread  or  culture  with  the  disin- 
fectant, into  stich  a  quantity  of  new  noninfected  medium  as  to  insure  a 
dilution  bevond  the  inhibiting  point,  which  may  be  due  to  any  of  the 
antiseptic  carried  over  on  the  thread  or  on  the  platinum  loop.  Thus, 
if  a  thread  has  been  exposed  to  a  solution  of  an  agent, — say,  in 
the  strength  of  i  :  loo, — and  the  inhibiting  action  is  present  in  a  solu- 
tion having  a  strength  of  i  :  looo,  it  will  be  necessary  to  carry  the 
thread  into  a  medium  having  a  minimum  bulk,  in  order  to  be  safe,  of 
at  least  loo  times  the  quantity  carried  over  on  the  thread,  thereby  as- 
suring such  dilution  as  not  to  preclude  the  disinfectant  preventing 
growth  of  any  undestroyed  organism. 

In  testing  gases,  threads,  cultures,  and  other  infected  materials  are 
exposed  to  the  gas — either  pure  or  with  a  known  dilution  of  air — in 
a  closed  chamber,  such  as  a  bell-jar. 

In  addition  to  the  foregoing  system  of  tests,  so-called  practical  tests 
are  made.  A  known  quantity  of  pus,  blood,  sputum,  or  feces  is  mixed 
with  a  known  quantity  of  the  disinfectant,  and  inoculations  made  at 
intervals  of  from  two  to  five  minutes.  Varying  strengths  of  the  disin- 
fectant are  used  with  exposure  for  different  lengths  of  time ;  in  this  way 
purelv  laboratory  experiments  are  controlled  by  what  are  considered 
practical  methods. 

Again,  animals  may  be  inoculated  with  cultures  or  threads  that  have 
been  exposed  to  disinfectants.  In  the  latter  case  it  is  to  l)e  rememliered 
that  in  rare  instances  the  pathogenicity  may  be  reduced  without  the 
germ  being  destroyed. 

To  study  the  pathogenesis  of  an  organism  inoculation  of  animals  is 
necessary.  The  animals  most  used  are  rabbits,  guinea-pigs,  rats,  and 
mice.  The  absolute  requisite  to  success  is  careful  asepsis  at  ever\'  stage 
of  the  process,  and  during  the  postmortem  if  the  animal  dies.  If  the 
disease  or  a  disease  is  produced,  and  it  is  desired  to  obtain  cultures,  they 
must  he  secured  with  the  same  strict  attention  to  detail. 

All  instruments  used  in  the  various  stages  of  inoculation,  examina- 
tion during  life,  or  postmortem,  should  be  sterilized  by  heat:  preferably 
dry.  although  moist  heat  may  be  used.  Chemic  disinfection  must  be 
regarded  with  suspicion,  although  syringes  may  be  sterilized  in  a  five  per 
cent,  solution  of  carbolic  acid  allowed  to  act  for  one  or,  better,  two  hours, 


924 


GENERAL    LABORATORY    TECHMC. 


Fig.  447. — Apparatus  for  Holding  a  Mouse  or  Rat  for 
Inoculation.  (Devised  by  Dr.  Lydia  Rabinowitsch 
and  Dr.  Voges.) 

The  inoculation  is  usually  made  just  over  the  root  of  the 
tail. 


during  which  time  the  solution  should  be  kept  warm.  Pure  formalin 
may  be  used  on  instruments.  No  matter  what  chemic  body  is  used,  it 
must  be  thoroughly  removed  by  washing  in  sterile  water  before  pro- 
ceeding with  the  operation.  The  hands  of  the  operator  and  of  the 
assistants,  and  the  table  upon  which  the  operation  is  to  be  conducted, 
should  be  washed  with  soap  and  water  as  hot  as  can  be  tolerated, 
followed  by  alcohol,  ether,  and  finally  corrosive  sublimate  solution  (i 
part  of  the  salt  dissolved  in  1000  parts  of  normal  salt  solution),  which 

should  be  allowed  to  act  several 
minutes,  followed  by  thorough 
washing  in  sterile  water. 

Of  the  many  methods  for  in- 
oculating an  animal,  the  follow- 
ing will  be  found  useful : 

I.  Subcutaneous    inoculation 
is  the  one  most  frequently  used. 
The   site    of    the    contemplated 
operation  is  shaved,  washed  with 
soap  and  water,  water,  alcohol, 
ether,  alcohol,  and  corrosive  sub- 
limate  solution    (i  :  1000),   and 
the  last   removed  by  thorough 
washing  with  sterile  water.     Between  the  scapulas  and  near  the  tail  are 
the  most  convenient  sites  for  inoculation,  but  any  point  where  the  tissues 
are  lax  will  answer  the  purpose. 

The  skin  is  stretched  and  made  tense,  an  incision  or  pocket  is  made 
in  the  tissues  about  five  millimeters  to  ten  millimeters  in  length  and 
correspondingly  deep  under  the  skin ;  into  the  pocket  so  made  a  loop  of 
the  growing  organism  or  suspected  material  is  introduced,  after  which  a 
layer  of  sterile  cotton  is  laid  over  the  wound  and  a  thick  coating  of  col- 
lodion applied;  in  a  few 
minutes  this  will  dry; 
the  animal  is  then  liber- 
ated and  kept  with  an 
uninoculated  animal 
known  as  the  control. 
Subcutaneous  injection 
of  bacteria,  suspended 
in  sterile  water  or  bouil- 
lon, may  be  resorted  to 
as  directed  for  intraperi- 
toneal inoculation. 

2.  Intraperitoneal  in- 
jections are  made  by  preparing  the  animal  as  before.  A  syringe  graduated 
in  cubic  centimeters  is  necessary  for  this  method.  The  skin  of  the  ab- 
dominal wall — the  site  of  the  operation — is  prepared  as  previously 
directed,  grasped  by  an  attendant,  and  raised  as  a  fold,  into  which  the 
needle  is  introduced  and  forced  onward  into  the  peritoneum,  then 
partly  withdrawn  to  make  sure  it  is  free  in  the  peritoneal  cavity. 
The  syringe  is  now  attached,  a  given  quantity  of  bouillon  culture  is 
introduced,  and  the  wound  is  sealed.  Rosenau^  has  greatly  im- 
^  Hygienic  Laboratory  Bull.  No.  19,  1904. 


.  44S. — K'ich's  Svrtxge  for  Hypodermic,  lNTRAPERiTi>xFAL,  and 
OTHER  Injection  Methods  for  Inoculating  A^^MALs■,  the 
Capacity  Should  Be  About  Two  Cubic  Centimeters. 


BACTi;kU)L(.)eiic  T];ciinr'.  925 

])roveil  the  KulIi  syringe,  and  describes  a  method  foe  .i>>,uiiii^  .nc  urate 
dosage. 

?.  Intravenous  iiiocitlatioii  is  made  directly  into  a  vein;  the  most 
convenient  veins  are  tliose  of  the  rabbit's  ear.  Tlie  overlying  skin  is 
l>repared  as  already  directed,  and  an  incision  is  made  down  ui)on,  but 
not  into,  the  vein;  wlien  the  vessel  is  thoroughly  exposed,  the  needle 
of  the  hypodermic  syringe  is  thrust  into  the  vein  in  the  line  of  the  blood- 
eurrent,  ami  the  contents  of  the  syringe  slowly  injected.  Cireat  care 
must  be  used  to  see  that  no  air  enters  the  vein,  and  that  no  clumps  or 
other  solid  material  that  might  cause  embolism  are  thrown  into  the  blood. 

-/.  I)iocnlatioii  i)ito  the  Anterior  Chamber  of  the  Eye. — Anesthetize 
the  cornea  by  cocain.  wash  with  sterile  water,  perforate  the  cornea  at  the 
scleral  margin  with  a  hypodermic  needle,  through  which  the  material 
is  injected;  the  rjuantity  should  be  very  small — scarcely  a  half  drop; 
otherwise  a  disturbing  tension  is  created  that  greatly  modifies  the  result 
of  the  operation. 

5.  Tissue  Iinphmtation. — Sometimes  (as  in  glanders  and  tubercu- 
losis) a  small  piece  of  the  suspected  tissue  is  used  for  inoculating.  The 
implantation  may  be  made  into  the  subcutaneous  tissues  or  serous 
cavities.  In  the  first  instance  a  pocket  is  prepared  as  already  directed 
for  subcutaneous  inoculation,  into  which  the  block  of  tissue  (which 
should  not  be  larger  than  from  two  to  five  millimeters  cube — the  smaller 


(r__ZrrjErr=3 

f'iG.  440- — Spatvla  Used  for  Searing  the  Surfaces  of  Organs  Before  Making  Incisions  into  Their 
Interiors  for  Obtaining  Culture  Material. 

the  better)  is  implanted,  the  wound  sealed,  if  necessary,  sutured,  and 
covered  as  already  directed.  For  transplantation  into  a  serous  cavity, 
the  peritoneum  is  usually  selected.  Under  the  strictest  asepsis  the 
cavity  is  opened,  the  tissue  dropped  in,  and  the  opening  closed.  In 
some  instances,  in  order  to  assure  vascularization,  a  tip  of  the  omentum 
is  brought  out,  the  block  of  tissue  rolled  in  the  serous  membrane,  and  the 
roll  secured  by  a  stitch.  The  foregoing  methods  demand  the  use  of  a 
piece  of  tissue  of  macroscopic  proportions,  and  leave  a  wound  through 
which  accidental  infection  may  occur.  In  many  instances  the  diffi- 
culties just  indicated  may  be  evaded  by  rubbing  up  the  material  in  a 
sterile  glass  mortar  with  a  small  fiuantity  of  sterilized  water.  Unless 
there  is  an  unusual  amount  of  connective  tissue,  the  maceration  may  be 
sufficient  to  permit  of  injection  through  a  medium-sized  hypodermic 
needle.  When  there  is  reason  to  believe  that  the  water  may  act  del- 
eteriously,  some  other  menstruum,  such  as  normal  salt  solution  or  Itlood- 
serum,  may  be  used. 

6.  Inhalation. — By  means  of  an  atomizer  bacteria  suspended  in 
water  or  other  liquid  medium  are  sprayed  in  such  a  manner  that  inhala- 
tion seems  reasonably  certain.  So  administered,  necessarily  many 
enter  the  alimentary-  canal  and  infection  by  that  pathway  may  occur. 
For  large  animals  (dogs,  cattle,  and  horses)  it  is  possible  to  introduce  a 
tube  past  the  epiglottis  and  in  that  way  infect  the  trachea;  usually 
tracheal  infection  is  best  accomplished  by  exposing  the  trachea  in  the 


926  GENERAL  LABORATORY  TECHNIC. 

neck  and  injecting  the  bacteria  directly  into  the  tube.     The  lung  may 
be  infected  through  the  chest  wall  by  hypodermic  injection. 

7.  Infection  by  the  reproductive  or  genito-nrinary  system  is  rarely 
practised. 

8.  Feeding  experiments  are  frequently  employed.  The  bacteria 
from  cultures  or  in  the  dried  form  are  distributed  on  food,  or  infected 
tissues  may  be  fed.  When  the  gastric  juice  would  probably  destroy  or 
render  inert  the  particular  germ,  the  stomach,  before  the  experiment, 
may  be  washed  out,  or  the  gastric  acidity  neutralized  by  weak  alkaline 
solutions.  Less  commonly  the  action  of  the  stomach  is  evaded  by  a 
laparotomy  and  direct  intestinal  deposit  of  infectious  material. 

Q.  Infection  of  joint  cavities,  bones,  muscles,  etc.,  may  be  attempted 
in  ways  similar  to  those  for  subcutaneous  and  intra-abdominal  inocula- 
tion. 

10.  Intracranial  inoctdation  is  performed  in  the  following  manner: 
Shave  and  antisepticize  the  scalp  in  the  parietal  region;  with  sterile 
hands  and  instruments  raise  a  V-shaped  flap  of  skin  twice  the  size  of  the 
trephine  to  be  used;  with  a  trephine  0.5  cm.  in  diameter  remove  a 
button  of  bone,  exposing  the  dura;  if  a  mass  of  tissue  is  to  be  inserted, 
open  the  dura,  introduce  the  tissue,  and  close  the  dura  with  a  suture. 
Fluid  or  finely  emulsified  tissue  may  be  injected  with  a  syringe  without 
incising  the  membrane.  Suture  the  skin  and  seal  with  antiseptic 
dressing. 

After-treatment  of  the  Animal. — Medication  of  all  kinds  should  be 
avoided;  overcome  the  immediate  shock  by  the  gentlest  handhng  of 
the  animal,  abundance  of  fresh  air,  and  warmth.  It  should  be  treated 
exactly  as  a  control  (an  uninoculated  animal  of  the  same  species),  but, 
as  a  rule,  should  be  in  a  cage  or  inclosure  by  itself;  otherwise  the  control 
may  injure  the  inoculated  animal. 

The  Postmortem. — If  the  animal  dies,-  the  body  should  at  once  be 
washed  with  soap  and  water  and  with  water  and  alcohol,  and  immersed 
in  I  :  1000  corrosive  sublimate  solution,  followed  by  washing  with  sterile 
water.  A  postmortem  is  made  under  strict  asepsis.  (See  also  p.  29.)  As 
soon  as  the  heart  is  exposed,  a  spot  on  the  surface  of  the  right  auricle  is 
seared  by  laying  a  heated  spatula  upon  it ;  this  thoroughly  disinfects  the 
surface.  Thrust  a  sterile  inoculating  needle  into  the  auricle,  moving  it 
through  the  blood  backward  and  forward  until  a  drop  emerges  along  the 
side  of  the  needle,  when  it  is  withdrawn  and  a  tube  of  medium  inoculated, 
which  may  be  at  once  poured  into  a  plate.  (See  Plate  Methods.)  This 
operation  is  repeated  for  each  cavity  of  the  heart  and  for  all  important 
organs  of  the  body.  Pieces  of  tissue  are  hardened,  either  in  absolute 
alcohol  or  corrosive  sublimate,  and  prepared  for  sections  in  the  usual 
manner.  (See  Killing  and  Fixing  of  Tissues,  p.  2,Z\  also  Staining  of 
Bacteria,  p.  911.) 

Preparation  of  Toxins  and  Antitoxins. — The  preparation  of  the 
diphtheria  and  tetanus  antitoxins  is  as  follows:  The  bacilli  are  grown 
in  flasks  (i  L.  to  2  L.)  of  bouillon,  which  in  the  case  of  tetanus  must  be 
arranged  to  assure  anaerobiosis.  For  the  satisfactory  production  of 
diphtheria  toxin  the  bacilli  should  be  grown  in  a  thin  stratum  of  an 
alkaline  glucose-free  bouillon;  the  maximum  strength  usually  is  attained 
during  the  second  week.  Filter  through  a  Pasteur-Chamberland  filter, 
preserve  in  well-stoppered  bottles,  and  keep  in  a  dark  place.     In  doses 


HACTERIOI.OGIC    TBCHNIC. 


92; 


of  0.0 1  CA-.  this  fillrate  should  kill  a  ^uinea-pij^  wcij^hinj,'  500  grams  in 
from  forty-ciijht  to  sixty  hours.  For  the  j)uri)ose  of  immunizing  animals, 
this  tiuid  is  in  many  cases  too  strong  for  the  first  injections,  and  should 
be  diluted  with  one-fourth  its  volume  of  Gram's  solution.  Roux  and 
Vaillard  have  determined  that  the  toxin  is  much  less  dangerous  when 
combined  with  iodin.  For  experimental  studies  small  laboratory 
animals  (rabbits)  may  lie  used,  but  for  the  production  of  antitoxin  on  a 
larger  scale  animals  able  to  supply  more  serum  are  necessary;  horses, 
cows,  sheep,  and  goats  are  commonly  selected.  The  weakened  or 
modified  toxin  is  administered  hypodermatically  at  first,  but  after  a 
relatively  high  degree  of  resistance 

has  been  attained  it  may  be  given  TjTT 

intravenously.  Toward  the  end  of 
immunization  bacteria  themselves 
may  be  injected.  The  injection  is 
repeated  in  a  few  days,  and  thus 
continued  for  several  weeks.  With 
each  successive  injection  the  pro- 
portion of  Gram's  solution  should 
be  diminished,  and  the  dose  slightlv 


Fig.  450. — Sternberg's  Flask,  Useo  for  Collect- 
ing Fluids,  Water,  etc.,  and  for  Holding  Cil- 
TVRF-S  in  Lkjuid  Culture  Media. 

Before  using,  it  is  sterilized  in  the  hot-air  oven.  To 
fill,  the  point  is  broken  off  and  the  bujb  is  heated, 
thus  txix-UinR  some  of  the  contained  air;  the  point 
is  then  thrust  into  the  fluid,  and,  as  the  bulb  cools, 
the  fluid  rises  into  it;  when  the  desired  qiiantity  is 
drawn^inlo  the  bulb,  the  point  is  sealed  in  a  gas- 
flame.  Certain  branfis  of  antitoxin  arc  now  dis- 
fK-nsed  in  bulbs  similar  to  the  one  here  illustrated. 


Fig.  451. — K.iiA.-.Aio'3  liLitK. 
The  material  to  be  tiltcred  is  placed  in  the  upper  bulb, 
which  is  connected  with  the  central  bougie  of  un- 
glazeii  iKjnelain.  The  point  of  connection  between 
the  receiving  chamber  and  the  filter  bougie  is  cov- 
ered by  a  rubber  cork,  which  fits  vcr>-  lightly  into 
the  neck  of  the  fl.isk.  Through  the  later.d  arm  of 
the  flask,  extending  out  to  the  right,  the  air  is  ex- 
hausted from  the  interior.  In  this  way  filtration, 
ordinarily  slow,  may  l>e  acccKrate<l  by  air  pressure. 
The  filter  is  mostly  used  for  s<'paraling  germs 
from  their  toxins. 


increased  until  the  pure  toxin  is  reached.  After  injection  of  the  toxin 
the  animal  not  infrecjuently  manifests  a  slight  rise  in  temperature,  with 
accelerated  pulse,  and  sometimes  an  evident  malaise.  A  second  injection 
should  not  be  given  until  all  symptoms  of  the  previous  injection  have  dis- 
appeared. The  amount  of  toxin  is  gradually  increased  until  the  animal 
bears  without  inconvenience  a  dose  equal  to  100  minimum  fatal  doses. 
If  during  this  time  a  loss  in  body-weight  becomes  manifest,  the  injections 
should  be  discontinued;    otherwise   a  fatal  cachexia   may  develop. 

The  horse  is  easily  immunized,  and  will  supply  large  quantities 
of  the  antidiphtheric  serum.  Horses  bear  proportionately  large 
doses  better  than  other  animals,  and  but  a  transient  fever  succeeds  a 
dose  of  from  two  to  five  cubic  centimeters  of  a  strong  toxin. 


928  GENERAL  LABORATORY  TECHXIC. 

Antitoxin  is  obtained  from  the  animal  by  bleeding  under  the  strictest 
conditions  of  asepsis,  receiving  the  blood  through  a  cannula  into  a  sterile 
jar,  flask,  or  other  container,  as  already  directed  for  the  preparation  of 
blood-serum  for  culture  purposes.  The  separated  serum  may  be  pre- 
served by  the  addition  of  tricresol,  thymol,  carbolic  acid,  camphor,  etc. 
It  should  be  sterile,  and  if  care  has  been  taken  to  exclude  contamination 
during  the  various  stages  in  its  preparation,  the  addition  of  a  preservative 
is  unnecessary.  The  milk  of  immune  animals  may  offer  an  important 
source  of  the  antitoxin. 

In  order  to  estimate  the  strength  of  an  antitoxin,  the  minimum  fatal 
dose  of  a  toxin  must  first  be  known.  This  information  is  obtained  by 
selecting  a  number  of  guinea-pigs,  each  of  which  weighs  250  gm.,  and 
by  injecting  subcutaneously  different  c|uantities  of  the  toxin  under 
investigation.  The  minimum  fatal  dose  is  that  which  kills  a  guinea-pig 
weighing  250  gm.  inside  of  four  days.  In  order  to  exclude  possible  error, 
arising  from  unusual  susceptibility  or  insusceptibility  of  the  animal,  a 
number  of  injections  should  be  made  and  a  fairly  uniform  result  finally 
attained. 

The  strength  of  the  antitoxin  present  in  the  serum,  obtained  as 
previously  described,  is  expressed  in  immunity  units.  An  immunity 
unit  is  the  quantity  of  antitoxin  which,  when  mixed  with  the  toxin, 
neutralizes  100  minimum  lethal  doses  of  the  latter.  For  the  pur- 
pose of  securing  a  uniform  strength  the  U.  S.  Government  now  sup- 
plies a  standard  serum  used  by  manufacturers  for  standardizing 
sera. 

A  number  of  test  doses  of  the  toxin  are  prepared,  each  containing 
a  hundred  times  the  minimum  fatal  dose.  To  each  test  dose  is  added 
a  measured  quantity  of  the  serum  in  question.  To  one  dose  is  added 
0.0 1  c.c.  of  the  serum;  to  another,  0.05  c.c.  of  the  serum;  to  another, 
0.1  c.c.  of  the  serum;  to  another,  0.5  c.c;  and  to  still  another,  i  c.c, 
and  so  on.  The  mixtures  are  now  injected  into  guinea-pigs  and  the 
results  observed.  Animals  not  dying  within  four  days  were  protected; 
local  infiltration,  wasting  or  death  after  the  fourth  day  does  not  enter 
into  the  computation.  The  mixture  containing  the  smallest  amount 
of  serum  and  yielding  this  result  contains  i  immunity  unit.  If  0.05 
c.c.  of  a  serum  neutralizes  one  hundred  times  the  minimum  lethal  dose, 
each  cubic  centimeter  contains  twenty  immunity  units.  Antitoxin,  as 
placed  upon  the  market,  is  labeled  as  containing  a  certain  number  of 
immunity  units,  and  the  measured  ciuantity  of  serum  necessarily  varies, 
as  the  number  of  units  obtained  are  rarely  exactly  the  same  in  two 
animals.  For  the  treatment  of  disease  the  antitoxin  is  administered 
subcutaneously. 

In  the  production  of  antitoxins  the  tissues  are  immunized  to  toxic 
agents  produced  by  the  bacteria,  while  upon  the  germs  themselves  there 
is  no  direct  action.  If  bacteria  or  other  cells  ar.e  injected  the  serum 
of  the  animal  acquires  the  property  of  attacking  the  bacteria  or  other 
cells  not  onlv  in  the  tissues  but  in  vitro  as  well.  The  protection  of  the 
organism  against  the  foreign  substances  is  accomplished  through  the 
intervention  of  substances  called  bacteriolysins  or  cytolysins,  and  the 
process  is  called  bacteriolysis  in  one  case  and  cytolysis  in  the  other. 
An  important  clinical  application  of  this  fact  is  in  the  diagnosis  of 
typhoid  fever.      Theoretic  considerations   are  discussed  elsewhere    (see 


HAlTKklOLDC.IC    TFXIIXIC.  ()2q 

discussion  on  imniunitv),  and  at  lliis  point  tin*  tcilinir  onl\'  tu'cd  \>v 
(.onsidoR'd. 

Widal's  Test  for  the  Diagnosis  of  Typhoid  Fever.'  (  itllitn-  Employed. 
— Tlio  culture  used  ni  tlie  Widal  test  should  l»c  taken  from  an  a^ar 
growth  that  has  l)een  allowed  to  develop  at  ordinary  rooni-temperaturc 
for  at  least  twenty  days.  From  this  aj^jar  culture  inoculations  arc  mafic 
into  tubes  containing  neutral  beef  bouill(»n,  and  these  tubes,  after 
incubation  at  37.5°  C.  for  from  eighteen  to  twenty-four  hours,  are  used 
in  the  test.  Instead  of  making  bouillon  growths,  emulsions  in  sterile 
distilled  water  may  be  used  with  good  results  by  thoroughly  mixing  a 
bit  of  a  recent  agar  growth  with  about  2.5  c.c.  of  sterile  water  in  a  test- 
tube  until  a  uniform  cloudiness  appears. 

The  precautions  previously  indicated  must  be  followed  to  avoid 
certain  false  or  pseudo-reactions,  which  sometimes  occur  when  normal 
blood  or  blood  from  individuals  suffering  from  diseases  other  than 
enteric  fever,  is  added  to  a  virulent  culture  of  the  typhoid  bacillus. 

Microscopic  Method. — The  blood  is  obtained  by  puncture  of  a  finger, 
and  three  separate  drops  are  allowed  to  fall  upon  the  surface  of  a  perfectly 
clean  glass  slide  that  has  been  passed  through  a  flame  and  cooled  just 
before  use.  The  glasses  are  permitted  to  dry,  and  arc  then  placed  in  a 
box  to  await  examination  at  a  convenient  time. 

To  one  of  the  blood-drops  a  large  drop  of  sterile  distilled  water  is 
added  to  effect  a  solution  of  the  dried  blood;  and  while  this  is  going  on, 
the  other  preparations  for  the  test  are  being  made,  by  cleaning  and 
sterilizing  by  the  tiame  two  cover-glasses  and  a  "concave  slide,"  to  be 
used  for  the  microscopic  examination  of  the  specimen. 

On  one  of  the  cover-glasses  six  drops  of  the  typhoid  bouillon  are  now 
placed,  and  to  this  is  added  a  large  drop  taken  with  a  platinum  loop 
from  the  summit  of  the  blood  solution,  and  the  whole  is  thoroughly- 
mixed  together.  From  this  mixture  of  blood  solution  and  typhoid 
bouillon  a  minute  quantity  is  now  placed  with  a  ])latinum  needle  upon 
the  center  of  the  second  cover-glass,  which  is  immediately  inverted  over 
a  hollow-cell  slide,  sealed  with  either  vaselin  or  cedar  oil,  and  examined 
under  the  microscope  with  a  J -inch  dry  objective.  (See  Hanging-drop 
Culture,  p.  918.) 

Instead  of  the  glass  slide  previously  recommended  for  receiving  the 
blood,  a  small  piece  of  highly  glazed  paper  may  be  substituted.  Whether 
using  the  glass  slide,  cover-glass,  foil,  or  paper,  the  blood  as  received  at 
the  laborator)-  is  dry,  and  the  difficulty  that  at  once  confronts  the 
investigator  is  to  restore  this  to  its  original  volume.  It  does  not  seem 
probable  that  accurate  restoration  is  ever  possible,  and  for  this  reason 
the  dry  method  must  always  be  liable  to  error,  depending  upon  our 

'  While  largely  used  in  laboratories  for  the  diaj^nosis  of  typhoid  fever  the  same 
principle  may  be  applied  to  the  diagnosis  of  paratyphoid,  colon  infections,  para- 
colon infections,  bacillary  dysentery,  Malta  fever,  and  with  less  hoix-ful  results 
to  cholera,  plague,  tulx;rculosis.  pneumonia,  meningitis,  anthrax,  etc  The  bibli- 
ography of  serum  diagnosis  is  most  e.xtensive.  (See  Craw.  "Jour  of  Hygiene." 
lanuarv,  IQ05;  Rostoski,  '.Manual  of  Serum  Uiagnosis,"  New  York.  1004:  Asa- 
kawa.  'Zeit.'f.  Hyg.  u.  Infectionskrank.."  xlv;  Scheller,  "Centralbl.  f.  Bakt.." 
Bd.  x.xxviii.  p.  loo;  Ficker.  "Berlin,  klin.  Woch."  190^.  Xo.  4s:  Borden.  "Medi- 
cal News,"  Slarch  18,  IQ05.  p.  485:  Wood,  "Chemical  and  .Microscooical  Diag- 
nosis." 1905.)  Full  review' of  the  subject  by  Rosenljerger  ( "Amer.  Med."  April 
16.  1904.  p.  621). 
60 


93° 


GENERAL  LABORATORY  TECHXIC. 


total  inability  accurately  to  determine  the  dilution  used.  The  majority 
of  observers  favor  a  dilution  of  not  less  than  one  part  of  serum  to  fortv 
parts  of  bacterial  suspension,  and  for  this  purpose  the  writer  is  not  familiar 
with  any  method  that  possesses  advantages  over  that  devised  by  Cabot. 
A  drop  of  blood  is  placed  in  a  tube  or  other  container,  and' at  once, 
using  the  same  pipet,  nineteen  drops  of  sterile  water  are  added.  In 
the  laboratory  the  cells  are  sedimented  and  one  drop  of  the  clear  fluid  is 
mixed  with  one  drop  of  a  bouillon  culture  or  aqueous  suspension  of 
typhoid  bacilli,  giving  as  nearly  as  can  be  obtained  a  dilution  of  i  :  40. 
If  not  unnecessarily  agitated,  the  corpuscular  elements  will  lie  mostlv 
at  the  bottom,  and  the  supernatant  fluid  may  be,  in  a  short  time,  clear. 
When  the  mixture  has  not  cleared,  sedimentation  may  be  hastened  bv 
the  use  of  the  centrifuge.  Accurate  dilution  may  be  assured  bv  the  use 
of  the  white  cell  pipet  of  the  Thoma-Zeiss  counting  apparatus.  The 
dilution  made  with  distilled  water  is  i  to  20;   this  mixture  is  blown  out 


Fig.    452. — B.^ciLLUs     Typhosus:     Widal's     Test; 

Negati\'e  Reaction. 
Hanging-drop  culture,  prepared  as  directed  on  page 

918.     The  bacilli  are  actively    motile  throughout 

Ibe  field. 


Fig.    453. — Bacillus    Typhosus;     Widal's    Test; 

Positive  Reaction. 
Large  clumps  of  motionless  bacilli  separated  by  open 

spaces.     The    few    bacteria  outside    the    clumps 

are  devoid  of  motility. 


into  a  small  pipet  or  tube,  which  is  sent  to  the  laboratory  and  examined 
as  directed  above. 

The  time  limit  is  as  important  as  the  dilution;  usually,  by  the  micro- 
scopic method,  if  the  reaction,  in  dilutions  of  i  to  40  or  i  to  50,  is  ruot 
well  advanced  or  complete  in  thirty  minutes,  the  test  may  be  con- 
sidered negative. 

Appearance  of  the  Reaction. — If  the  reaction  is  positive  large  clumps 
of  motionless,  agglutinated  bacilli,  which  appear  as  irregularly  shaped 
islands,  separated  by  open  spaces  containing,  perhaps,  a  few  isolated 
bacteria,  whose  power  of  propulsion  is  either  decidedly  inhibited  or 
entirely  lost. 

If  the  reaction  be  negative,  the  bacilli  appear  as  actively  motile  rods, 
darting  across  the  field  in  ever}'  direction  and  showing  no  tendency  to 
form  into  masses,  although  occasionally  small  clumps  of  the  micro- 
organisms may  be  noted.  In  negative  reactions,  however,  clump 
formation  never  progresses  to  any  marked  degree,  and  motility  persists, 
regardless  of  the  time  during  which  the  specimen  is  watched.     If  any 


H  ACT  K  RIO  I.oc;  I C    T  KC 1 1  \  IC 


9.?' 


doubt  exists  as  to  llu-  nature  of  a  reaetioti,  a  "control"  slide  sliouM 
be  prepared  with  normal  blood  and  tx'phoid  l>()uillon.  for  purpc^ses  oi 
eonijjarison.      (See  I'i.us.  452,  453.  454.) 

The  time  rc(|uired  for  the  completion  oi  a  reaction  varies,  but  in  a 
{general  way  it  may  be  said  that  typhoid  blood  will  cause  detinite  clump- 
injj  and  loss  of  motility  of  the  typhoid  bacilli  within  thirty  minutes 
in  the  great  majority  of  instances.  In  some  cases  a  longer  time  will 
be  necessary  before  a  correct  interpretation  of  the  test  can  be  made. 
.1  reaction  ttioy  not  be  classed  as  positive  unless  both  cliinip  jormation 
and  loss  of  motility  coexist,  and  those  reactions  in  lehich  either  of  the 
phenomena  are  icantiiii;  may  not  be  called  typical. 

For  the  macroscopic  method  small  test-tubes,  the  luniina  of  which 
should  not  exceed  0.5  to  0.7  cm.,  are  used.  The  examination  should 
be  made  in  series,  and  for  this  purpose  the  tubes  may  be  arranged  side 
by  side.  The  first  tube  should  contain  the  bacterial  emulsion  alone. 
The  second  tube  forty  parts  of  the  bacterial  emulsion  and  one  part  of 


I-'ic.  454. — Hacii.lcs  Typhmsl^;   W  iual's  Tkst;   .V  1'seudo-reaction. 
.\  few  small  clumps  of  bacilli  having  impaired  motility.     Persistent  motility  of  the  bacteria  in  other  parts  of  the 

Ik'ld  occurs. 


the  suspected  serum.  The  third  tube  receives  one  jtart  of  normal  serum 
and  forty  parts  of  the  liacterial  emulsion.  Ot'her  tubes  may  be  used 
containing  higher  dilutions  of  the  suspected  serum.  In  the  pres- 
ence of  a  positive  reaction,  the  bacteria  collect  in  minute  Hocculi  (ag- 
glutination) and  finally  fall  to  the  bottom  of  the  tube  (precipitation). 
The  reactif)n  should  be  complete  in  from  twelve  to  twenty-four  hours. 
Systematic  Records. — In  order  to  render  comparable  studies  made 
by  different  investigators,  as  w^ell  as  for  comparison  of  the  character- 
istics of  different  bacteria,  it  becomes  necessary  to  select  some  definite 
order  of  study  and  a  method  by  which  accurate  records  may  be  kept. 
The  method  which  follows  presents  nothing  original,  and  is  that  in 
use  in  the  laboratories  under  the  author's  supervision.  The  entire 
blank,  as  well  as  the  outline  drawings  of  culture  tubes  (b,  c,  d,  e,  table 
on  p.  932),  are  supplied  to  the  student,  and  on  these  blanks  he  draws 
in  black,  or  better  in  color,  the  cultural  })cculiarities  of  the  microorgan- 
ism under  investigation.  For  noting  the  changes  observed  in  the 
culture  fnim  day  to  day  the  drawings  made  each  iliv  .ire  kept,  and  the 


932 


GENERAL  LABORATORY  TECHNIC. 


entire  series  clamped  or  gummed  together  for  tiling.  The  table  not 
only  affords  a  satisfactory  means  for  recording  the  characteristics  of  an 
organism,  but  also  indicates  what  data  should  be  worked  out,  and 
the  usual  sequence  in  which  the  results  attained  are  recorded. 


TABLE    ILLUSTRATING    METHOD  OF  RECORDING    THE    PRINCIPAL 
CHARACTERISTICS  OF  AN  ORGANISM. 

(A)  Where  found. 

(B)  Morphology,      (a)  Form,  (6)  size,    (c)  arrangement. 

(C)  Stains.      Reaction  to  Gram's  inethod  of  staining. 

(D)  Motility  I  W   Si;-?,ate. 

(E)  Method  of  reproduction. 

(F)  Products  of  growth:  (a)  Acids,  (b)  alkalies,  (c)  odor,  (d) 
color,  (e)  gases,  (/)  enzyme,  (g)  indol,  (h)  toxin,  (i)  other 
chemicobiologic  reaction  or  product. 

(G)  Characters  of  growth  on:      (a)    Plates. 


Make  Drawing. 


fC:>    fCr^     FCC^    F^^ 


(b)  Bouillon. 


(c)  Gelatin. 


(rf)  Agar, 


(e)  Blood- 
serum. 


(/)  Spkcial 
Medium. 


BACTKKIOLOGIC    TKCIINIC.  933 

(H)    (a)   Aerobic.   (/-)   u.uic-rul.ic   -[i'*     ]-;=J^;"lt;^tivc. 

I  (2)     Obhj^ate. 
(I)    Reaction  of   inediiiin    Ivst    adapted  to  its  j^Towth.      Reaction  of  cultures 

in   milk. 

(j)    (a)    Optinuun   teinpeniture     (l>)    thermal    -kMlh-noint    M'v    ?!"''*'.   '^^'''*- 
,.,    ,     ,  ,  .  <  (2)    Drv  heat. 

(K)    Intluence   of  antisejitics  and   di.sinfectants. 
(L)    Pathoi^enesis 

(M)    Immunity,  method  of  securing,  duration,  blood  characteristics  in  and 
inrtuence  of  blood-serum  of  immune  animal  on  the  orrjanism. 

(S)    Remarks:    Peculiarities   not   embraced   in    foreijoing   fortn. 


CHAPTER  II. 
MICROSCOPIC  EXAMINATION  OF  URINE. 

Collection  of  Sample. — The  amount  of  urine  necessary  for  the  exami- 
nation depends  somewhat  upon  the  object  of  the  examination  and 
the  condition  of  the  urine.  In  most  instances  at  least  200  c.c.  should 
be  submitted  to  the  examiner.  For  chemic  examination  a  mixed 
twenty -four  hours'  sample  is  usually  recommended,  but  for  microscopic 
study  a  succession  of  samples  collected  at  different  hours  during  the 
day,  and  especially  morning  and  evening,  offers  certain  advantages. 
Bryson  has  shown  that  for  the  demonstration  of  tubercle  bacilli  resid- 
ual urine  offers  better  results  than  the  tidal.  It  is  well  known  that 
purulent  urines,  and  especially  those  rich  in  bacteria,  particularly  the 
colon  bacillus,  exert  a  lytic  action  on  structural  elements  coming  from 
the  kidney,  and  especially  on  casts;  such  specimens  should  be  examined 
shortly  after  voiding.  The  urine  should  be  collected  in  a  perfectly 
clean  bottle  and  delivered  at  once.  When  tubercle  bacilli  are  to  be 
looked  for,  or  when  any  bacteriologic  examination  is  contemplated,  the 
container  should  be  disinfected,  all  parts  of  the  external  genital  organs 
that  are  likely  to  come  in  contact  with  the  urine  should  be  cleansed  and 
the  urine  drawn  with  a  thoroughly  cleansed  and  sterile  catheter. 
Smegma  bacilli  are  so  abundant  in  the  external  genital  organs  of  the 
female  that  it  is  best  to  use  extra  precautions,  and,  if  possible,  to  re- 
move the  urine  by  means  of  a  glass  catheter  that  has  been  sterilized  in 
a  hot-air  oven  at  a  sufficiently  high  temperature  to  carbonize  any 
bacteria  that  may  be  upon  or  within  it.  As  soon  as  received,  the 
urine  should  be  sedimented.  This  may  be  accomplished  by  per- 
mitting it  to  stand  in  a  conic  glass,  such  as  is  shown  in  figure  456. 
A  better  and  more  convenient  means  for  securing  sedimentation  is  by 
the  centrifuge.  Of  the  various  forms  of  centrifuge,  those  in  which  the 
power  is  supplied  bv  the  hand  or  turbine  are  to  be  preferred. 

Method  of  Conducting  the  Examination. — As  soon  as  the  sediment 
has  been  secured  by  either  of  the  methods  previously  indicated,  a  sterile 
pipet,  closed  by  the  finger  at  the  upper  end,  is  cautiously  introduced 
through  the  supernatant  fluid  into  the  sediment;  the  finger  is  slowly 
drawn  to  one  side,  permitting  a  few  drops  of  sediment  to  enter.  The 
finger  is  then  held  tightly  over  the  pipet,  which  is  at  once  withdrawn 
from  the  urine.  The  fluid  on  the  outside  of  the  pipet  is  then  removed 
with  a  cloth  or  paper,  and,  holding  the  pipet  perpendicularly,  a  small 
drop  is  placed  on  the  slide  and  a  cover-glass  applied.  Drain  off  excess 
of  fluid  with  blotting-paper,  and  examine  with  f-inch  and  \-  or  -g-inch 
objectives.  While  a  number  of  methods  have  been  devised  by  which 
the  organized  constituents  of  urine  may  be  stained,  the  student  had 
best  familiarize  himself  with  unstained  preparations,  although  for 
special   purposes   staining   may   be   necessary.     An   important   precau- 

934 


MICROSCOPIC     KXAMINATION     OK    I'RINK. 


935 


tion  is  never  to  Hood  the  field  witli  li.^lit.  TIk-  illuiiiiiiation  should  he 
even  but  subdued;  an  excess  of  lij^dit  renders  hyaline  casts,  red  blood- 
cells  which  have  lost  their  henioj^dobin,  and  other  shadowv  structures 
invisible.  The  lis^dit  is  best  reduced  by  lessening  the  opcninj^  in  the 
iris  diaphrajjjni. 

Preservation  of  the  urine  may  be  aided  by  adding'  a  crvstal  of  thvmol, 
camphor,  or  menthol.  If  it  be  desired  to  preserve  the  sediment,  this 
is  best  accomplished  by  carefully  decanting  the  sujjernatant  fluid  and 
addinj^  an  ecjual  quantity  of  a  saturated  acjueous  solution  of  potassium 
acetate,  allowing  this  to  remain  forty-eight  hours,  again  decanting, 
and  adding  fresh  acetate  solution.  After  repeating  this  three  times, 
no  difficulty  will  be  found  in  preserving  casts,  Ijlood,  epithelium,  etc., 
present  in  the  sediment,  leasts  may  be  preserved  indefmitelv  in  chloral, 
provided  they  have  been  washed  according  to  the  methods  just  indi- 
cated. The  chloral  solution  should  have  a  strength  of  about  twentv 
grains  to  the  ounce  of  water,  and  should  exceed 
in  volume  one  hundred  times  the  volume  of  the 
sediment  to  be  preserved.  Fischel  preserves 
casts  in  a  mixture  of  equal  parts  of  glycerin 
and  distilled  water,  saturated  with  thymol.' 

()rg.\xized  Sediment  {Cellular  Constitu- 
ents).— Red  HlooJ-eorf>uscies. — When  these  cor- 
puscles occur  in  large  numbers  and  in  good  con- 
dition without  being  intimately  blended  with  the 
urine,  they  are  usually  from  the  bladder  or  ure- 
thra;  but  when  they  do  not  form  a  red  sediment 
after  many  hours'  standing,  and  have  lost  their 
coloring-matter  and  appear  as  pale  yellow, 
washed-out  rings  (phantom  corpuscles  of 
Traube),  especially  if  associated  with  blood- 
casts,  the  hemorrhage  has  probably  occurred 
in  the  substance  of  the  kidney,  renal  pelvis,  or 
ureters. 

Leukocytes  in  urine  are  usually  indicative  of 
some  inflammatory  condition  of  the  conducting 
passages.  They  rapidily  disappear  in  alkaline 
urines;  when  freshly  voided,  they  may  show 
ameVjoid  movement.  While  other  forms  arc 
not  infre(|uently  found,  the  polynuclear  usuall\ 
predominates.      Fragmented  and  granular  cells  are  commonly  present. 

Epitheliuni. — (Make    drawings    of    different    forms.) 
Squamous  epithelium. 
Transition  epithelium. 
Epithelium  from  bladder. 

Uriiuiry  Casts   (see   p.   639). 

I.  Those  consisting  of  cells. 
II.  Those  that  consist  of  the  products  of  cellular  change. 
III.   Hyaline  casts. 

'  For  the  permanent  preservation  of  tube  casts  for  microscoi)ic  mounts,  see 
Boston.  ■■  X.  ^  .  Med.  Jour."  Novemlx^r  4.  1809.  For  chemistry  of  tul^-casts  and 
other  details,  see  Coplin.  •Publications  from  the  LaV>oratories  of  the  Jefferson 
Medical  College  Hospital,"  1004.  vol.  i.  For  structure,  origin,  and  significance  of 
casts,  see  p.  639. 


Tig 
Ilu 


455.       WaII.K      ChMklKLut. 

number  of  rcvuluiions  <lc- 
[x-nds  on  the  water  pressure 
and  on  the  size  of  the  supply 
pipe.  .\  pilie  at  least  J  of  an 
inch  should  }>v  used.  The 
ordinary  city  pretv-sure  is  aUmt 
25  [xmnds;  with  }  inih  jiijx- 
this  will  ijive  1200  revolutions 
a  minute;  .^o  |x>unds  will  give 
1400;  is  |x>unds.  1500.  A 
thou.sani)  revolutions  a  min- 
ute are  sufficient  for  urine 
sedimentation.  Tubes  .\  and 
M  IimI.I  ;o.  .  .  rarh. 


936 


GEXERAL  LABORATORY  TECHXIC. 


Examine  with  i-inch  or  ^-inch  objective  and  make  drawings  of- 

Hlood-casts, 

Epithelial  casts, 

Granular  casts, 

Waxy  casts, 

Fatty  casts, 

Hyaline  casts, 

Pus-casts, 

Bacterial  casts, 

Cylindroids, 

False  casts,  composed  of  Pirates 
or  crystals. 

Casts  from  seminal  tubes. 
S  permatozoa     are      thread-like 
bodies,  50  ,«  long,  provided  with  a 
head  and  a  long,  tapering,  tail-like 
extremitv. 


Fig.  456. — Conic  Glass  Suitable  for  the  Sedi- 
mentation OF  Urine. — (Coplin  and  Bcoan.') 

In  position  is  shovs-n  a  candle-wick  filter  for  securing 
urinary  sediment.  The  filter  consists  of  a  glass 
tube  so  bent  that  the  longer  arm  is  outside  and 
opens  below  the  level  of  the  bottom  of  the  conic 
glass.  Through  the  bent  glass  tube  are  drawTi  a 
few  strands  of  candle-wick  to  fill  the  tube  rather 
tightly.  By  capillarity  the  urine  rises  in  the  bent 
tube  and  eventually  flows  over;  in  so  doing  it 
deposits  all  the  sediment  on  that  end  of  the  candle- 
wick  which  is  at  the  bottom  of  the  glass.  This  is 
gently  brushed  over  a  number  of  slides,  cover- 
glasses  are  applied  and  the  slides  examined  at 
once. 


Fig.  457. — Centrifuge  with  Hematocrit  Attach- 
ment. 

The  attachment  for  sedimenring  liquids  such  as  urine 
is  shown  in  position  for  use.  This  may  be  lifted 
off  and  the  hematocrit  attachment  shown  in  the 
upper  part  of  the  figure  substituted  in  the  place 
of  sedimenting  attachment  shown  in  position. 
There  are  two  gears,  one  for  sedimenting  blood, 
known  as  the  high  gear,  and  which  gives  10,000 
to  14,000  revolutions  a  minute;  the  lower  gear, 
for  sedimenting  urine,  giving  from  2500  to  4000 
revolutions  a  minute.  The  crank  is  easily  trans- 
ferred from  one  gear  to  the  other. 


Their  constant  deposit  indicates  spermatorrhea.  They  are  easily 
identified  in  urinary  sediment,  or  may  be  stained  as  follows:  Spread 
a  thin  laver  of  the  sediment  on  a  clean  cover-glass;  dry  without  heat; 
stain  in  carbolfuchsin  for  two  seconds ;  wash  in  water ;  dry,  and  mount 
in  balsam. 

Occasionally  fragments  of  papilloma  may  be  recognized  in  the  urine. 
If  the  specimen  has  been  drawn  with  a  catheter,  the  eye  of  the  instru- 
ment may  contain  shreds  of  such  growths. 

Nonpathogenic  Fungi: 

Molds,    or   large   segmented   rods. 


MICROSCOPIC     KXA.MINATION    OV    UKINK.  Q37 

Yeast  plants  (Sarcharoiiiyrcs  urina*  and  other  yeasts)  arc  arraii'/cil 

in  bead-like   forms   with    Imddin^'   iclls   attached. 
T^atteria  of  decomposition. 
Pathogenic   Fungi,  —  Ttibcrclc  Bacilli  (see  p.    144). — In   all   cases  of 
j)urulcnt  urine  accompanied  by  anemia,  wasting.  an<l  evening  rise  of 
temj)erature.  the  urinarv  sediment   should    be   examined    for   tubercle 
bacilli. 

Purulent  deposits  of  tul)erciilous  urine  should  be  treated  the  same 
as  sputum  in  searching  for  tul)ercle  bacilli.  The  centrifuge  aids  ma- 
terially in  this  examination.  (For  method  of  dcmonstratif)n  see  Tu- 
bercle Bacilli.) 

Go)iococct(s  (Xeisser,  see  p.  107). — Minute,  roll-shaped  diplococcus 
found  in  urine  containing  gonorrheal  pus.  (For  method  of  staining  and 
description  see  Gonococcus.) 

Distoma  Hccmatobium  (see  p.  193). — The  oval  eggs  of  this  parasite, 
about  125  «  by  40  /(,  spiculated  at  one  end,  are  found  accompanied 
by  blood-cells  and  pus. 

Filaria  Sanguinis  Hoiiiinis  (see  p.  207). — The  embryos  are  occa- 
sionally found  in  chyluria.     (See  Animal  Parasites.) 

UxoRCAXizi: I)   vSHniMKXT    (Crystalline    a}id    Auiorplions). 
Sediment  of  Acid  Urine. — (Examine  and  draw  the  various  crystals.) 
Uric  acid  (whetstone  crystals). 
Oxalate  of  lime  (envelop   crystals). 
Hippiiric  acid. 
Urate  of  soda. 
Tyrosin  and  lencin. 
Soaps   of  lime  and  magnesium. 
Amorphous  deposits. 
Urates. 

Hroien    and    yelloie    concretions. 
Sediment   from   Alkaline   Urine. 

Triple  phosphates  (cotfin-lid  crystals). 

Urates  of  Ammonium  (hedge-hog  crystals). 

Indigo. 

Cholesterin. 

Amorphous  deposits. 

Phosphate  of  lime. 

Carbonate  of  lime. 


93S 


GENERAL  LABORATORY  TECHNIC. 


ILLUSTRATIONS  OF  VARIOUS  URINARY  SEDIMENTS.^ 


(?9 


?ep 


o 


o 


Fig.  4s8. — Phantom  and  Dis- 
torted Red  Blood-cells 
Found  in  Urine,  Most 
Commonly  That  of  Renal 
Hematuria. — (Landois.) 


®%  *    ^       ^  ^%^ 

(3*    ^    ®  c       O    "(ji 

•    ^''-'   ^©^»®®^ 

Fic.  459. — Blood-cells  in  the 
Urine. — (Gould.) 

The  cells  that  appear  almost  nor- 
mal could  not  have  been  sub- 
jected to  the  action  of  the 
urine  but  for  a  short  time. 


Fig.  460. — Blood-cells  in  the 
Urine,  Lymph-corpuscles, 
Leukocytes  or  Pus-cells,  and 
Crystals  of  Triple  Phos- 
phate. X  350  diameters. — (Lan- 
dois.) 


Fig.  461. — Epithelium  from  the  Conducting  Part 
OF  the  Urinary  Apparatus,  Mostly  from  the 
Bladder. 

Note  in  the  upper  right  quadrant  of  the  figure  the 
cells  that  resemble  renal  epithehum. 


Fig.  462. — Epithelium  of  the  Renal  Type. 
The  four  cells  below  and  to  the  left  are  fatty.  This 
form  of  epithelium  will  be  found  on  casts  and 
free  in  the  urine.  It  will  be  noted,  however,  that 
it  so  closely  resembles  epithelium  from  one  layer 
of  the  conducting  apparatus  that  the  diagnosis  of 
free  renal  epithelium  must  always  be  open  to 
criticism.  See  figure  461,  epithelium  from  the 
bladder. 


'  Experience  has  convinced  the  writer  that  the  best  way  to  learn  to  recog- 
nize the  various  urinary  sediments  is  to  take  as  good  an  illustration,  or  series  of 
illustrations,  as  can  be  secured,  and  work  at  the  microscope  with  the  illustrations 
at  hand  until  able  to  recognize  all  the  ordinary  forms. 


MICROSCOPIC    EXAMINATION    Ol'    URINE. 


939 


Fig.  463. — Semixai.  Elements,  Some  of  Which  Mav  Be  Found  in  L'rine. 
a,  a.  Spcrmatoxo.i.     b.  Seminal  cells,    e.  Epithelium,     d,  d.  Seminal  gr.Tnules. 


Fic.  464. — Illvstrati.ng  the  Formation  of  Casts  . 
(Rindflfisch.) 

a.  Hyaline  cast  in  place.  If  it  comes  away  bringinn 
nothinK  n-ith  it.  it  will  remain  a  hyaline  cast.  If 
it  brinns  epithelium,  it  will  t>c  an  epithelial  cist; 
if  the  epithelium  is  granular,  it  will  be  a  KTanular 
cast;  if  fatty,  a  fatty  cast.  c.  Granular  cist.  The 
two  casts  in  the  lower  comer,  and  to  the  left,  are 
hyaline'  the  remaining  casts  are  largely  hyaline, 
but  bear  a  few  epithelial  cells. 


Fig.  465.— Epithelial  CA^i  

Epithelial  cast,  the  lower  en<l  of  which  is  coarsely 
eriinuLv.  B.  Epithelial  ca.M  in  which  the  epithe- 
lial cclU.  thougn  themselves  granubr,  have  not 
broken  up. 


940 


GENERAL  LABORATORY  TECHNIC. 


t)^^a 


Fig.  466. — Blood-cells  and 
Blood-cast. — {Landois.) 


Fig.  467. 
.4.  Hyaline  cast.  iS.  Hyaline 
cast  with  a  few  attached 
leukocytes.  C.  Hyaline 
cast  with  attached  epithe- 
lium, truly  an  epithelial 
cast. — {Landois.) 


Fig 


— Granular  Casts. — {Landois^ 


Granular  casts  in  which  the  granules  are 
fine  and  the  dissolution  of  the  epithelial 
cells  is  complete.  B.  Granular  casts  in 
which  the  granules  are  coarse  and  the 
outlines  of  the  epithelial  cells  at  points 
faintly  distinguishable. 


Fig.  469. 
A.  Cast  made   up  almost  purely   of  leukocytes.     B. 
Casts  composed  of  acid  sodic  urate;  crystalline 
casts. — (Landois^ 


«^/ 


Fig.  470. 
a,  a,  b,  c.  Crystals  of  uric  acid,     d,  g.  Zooglea  masses 
of  cocci  and  bacilli,     e.  Mold.     /.  Yeast. — (Lan- 
dois.) 


MICROSCOPIC    EXA.MINATIO\    OF    URINE. 


941 


Fig.  471. — Some  Forms  of  Uric  Aao. 
Rhombic  cnslal?.    2.   Whetstone  forms.     3,  3.  Quadrate  fonns.     4,  4,  .5.  Irregular  forms.     6,  8.  Groupings 
into  roset  forms.     7,  0.  Bundle  forms,  precipitated  by  adding  hydrochloric  acid  to  the  urine.     The  crj-stals 
may  be  pigmented  or  lightly  colored  brownish-yellow;  the  pigment  is  presumed  to  be  uroerythrin,  also  called 
urochrome. — (Landois.) 


Fig.  472- — AaD  .'\mmo.nii'ji  Urate. 


Fig.  473.— HiPPi  rk  .\c\v.     Fuirsided  Prisms  with 
Two  OR  FoLR  Beveled  Edges. — {Gould.) 


942 


GENERAL    LABORATORY    TECHNFC. 


Fig.  474. — Some  Deposits  in  Acid  Fermentation  of  the  Urine. — (Landoit.) 
a.  Bacteria.     6.  Amorphous  sodic  urate,     c.  Uric  acid.     d.  Calcium  oxalate. 


Fig.  475. — Some  Deposits  from  Ammoniacal  Urine  (Alkaline  Fermentation). 
a.  Acid  ammonium  urate,     b.  Ammoniomagnesium  phosphate,     c.  Bacteria. 


Fig.  476. — Whetstone  and  Irregular  Crystals  of        Fig.  477- — Ammonium  Ur.ate.    "Hedge-hog"  Crys- 
Uric  Actv.— (.Gould.)  J ALS.— (Gould.) 


MICkOSCOl'M      1.  \  AM  1  .\  A  1  IMN     (II      ri<iNi; . 


943 


Fic.  478. — Stellate  and  Feathery  Crystals  of  Triple  Phosphate.— (Tyson.) 


Fic.  479. — Forms  of  Crystals  of  thf  .■XMiioMfiMAr.NE.siirM  Phosphate. — (7"yjo«.) 


0  ^ 


m 


l-i...   4^0        \mm"M '■  \i  A  ..  \  r  -  I  f  M  hit..      4^I 

Phosphate    (Tripi.e   Phos-  ph a  1 

PHATE).— (C»«W.)  Elong.iic<l  rli 
Triangular  prisms  with  leveled  edges;  mav  l>e  fu>cl  '.w^t  :iii  r  in  v  ^ri 

"coffin-lid  "  crystals.  ouOv  form»-H  m.i*!*^. 


'  ^      liRAN- 

w  Cakbon- 


944 


GENERAL  LABORATORY  TECHNIC. 


Fig.  483. — Oxalate  of  Lime. 


Fig.    484.— .•Xmorphous    Gran-  Fig.   485. — Dumb-bell    and    Octa-  Fig.  486. — Calcium    Sulphate; 

ULES,  Wedge-shaped  Crys-  hedral  Crystals  of  Calcium               Elongated      Transparent 

TAI.S,    SOME    Arranged    in  Oxalate. — (Gotild.)                                   Needles     or     Tablets. — 
Rosets  of  Calcium    Phos-                                                                                   {Gould.) 
PHATE. — (Gould.) 


Fig.  487. 
a.  Crystals  of  cystin.     *.  Crystals  of  o.xalate  of  L'me.     c.  Hour-glass  forms  of  b. 


MICkOSCOl'IC    EXAMINATIOM    OF    rUINK. 


945 


Fig.  488. 
a.  Lcucin  balls      h,  h.  Tyrosin  sheaves. 


Fig.  489. — Leucin  and  Tyrosin.  Fig.  490.— Cystin,  Six-sided  ri.ATEs,  Often  Super 

.1    A.  Leucin;    yellowish     highly    refractinR    spheres.  imposed.— (Go«W.) 

with  radiating  lines.     B,  B.  Tyrosin.  needles  and 
sheaf. 


Fig.  49 1 .— Cholesterin.— (iunrfoij.) 
61 


Fic.  4oi.— Indigo.— ((;(»i«/</.) 

Amorphous  krr.mults.  fine  needles,  and   rryst.ils  of  a 

'lue  color. 


CHAPTER  III. 

TECHNIC  OF  SPUTUM  EXAMINATION. 

Collecting  the  Specimen. — Great  care  should  be  exercised  in  ob- 
taining the  sputum  for  examination.  Sputum  collected  immediately 
after  eating  usually  contains  particles  of  the  food,  which  unnecessarily 
complicate  the  examination.  The  first  sputum  raised  in  the  morning 
is  to  be  preferred.  The  patient  should  be  instructed  to  avoid  collect- 
ing mucus  brought  from  the  nose  and  pharynx.  Findlay  obtains 
sputum  from  young  children  by  wrapping  the  finger  with  a  piece  of 
gauze,  irritating  the  epiglottis  by  the  gauze-wrapped  finger,  and  sweep- 
ing out  of  the  mouth  any  sputum  that  results  from  the  induced  cough- 
ing. The  amount  of  sputum  to  be  obtained  will  vary  with  circumstances : 
while  a  very  small  amount  may  be  examined  and  give  satisfactory 
results,  five  or  ten  cubic  centimeters  or  more  should  be  obtained  when 
possible.  The  patient  should  expectorate  directly  into  a  small  stone 
cup  or  sterilized  salt-mouth  bottle;  as  soon  as  a  sufficient  quantity  of 
sputum  has  been  collected,  the  container  should  be  at  once  sealed  with 


Fig.  493. — Squamous  Epithelium. 
Often  found  in  sputum  and  in  urine.     In  the  former  it  is  from  the  mouth  or  pharynx.     In  urine  it  is  usually  from 

the  vagina. 

adhesive  plaster  or  tightly  corked,  and  labeled.  When  ready  for  ex- 
amination, the  sputum  should  be  poured  upon  a  piece  of  ordinary 
window  glass  with  the  under  side  painted  black,  or  into  a  Petri  dish 
placed  over  a  blackened  surface.  Upon  this  black  surface  the  small, 
white,  opaque  portions,  which  are  best  for  examination,  can  be  readily 
seen,  removed  by  forceps  or  platinum  hook,  and  placed  in  the  center 
of  a  glass  slide.  A  cover-glass  is  laid  on  the  specimen,  and  slight  pres- 
sure made  to  obtain  a  uniform  layer. 

White  blood-corpuscles  are  always  present  in  sputum;  eosinophiles 
occur  in  certain  forms  of  asthma  and  chronic  bronchitis,  and,  accord- 
ing to  Teichmiiller,  in  two-thirds  of  the  cases  of  pulmonary  tubercu- 
losis; in  the  latter  condition  he  believes  they  have  some  prognostic 
value,  being  most  abundant  in  patients  that  are  doing  well. 

Red  Blood-corpuscles. — Their  presence  in  small  numbers  is  not 
significant.     In   pneumonia    they   occur   as   pale,    discoid   bodies,    and 

946 


TECIINIC    OF    SPUTUM    EXAMINATION'. 


947 


in  hemoptysis  tlie  si)utum  may  consist  almost  entirely  of  red  cor- 
puscles. 

Epithelium. — Squamous,  from  the  mouth. 

Ciliated,  usually  from  the  trachea  and  bronchi. 

Alveolar,  from  the  alveoli  of  the  lungs. 

Elastic  Fibers. — When  these  fibers  display  an  alveolar  arranjjement, 
they  have  been  ilerived  from  the  i>ulmonary  alveoli,  and  indicate  a 
destruction  of  lung  tissue. 

They  occur  in  tuberculosis  and  bronchiectasis,  and  occasionallv  in 


Fic.  494. — CcRscHMAxs's  Spirals. — {Schmaus.) 
a.  X  80  diameters.     6.  X   300  diameters. 


pulmonan.'  abscess,  gangrene  of  the  lung  (some  cases),  pneumonia 
and  destructive  processes  attacking  the  air-passages  and  lungs.  The 
slide  of  sputum  is  prepared  in  the  usual  way,  and  examined  with  a 
|-inch  objective.  The  elastic  fibers  exhibit  a  double  contour,  are 
dark  colored,  slightly  curved,  and  vary  much  in  length  and  breadth. 
They  can  be  most  readily  collected  for  demonstration  by  rapid  sedi- 
mentation in  a  centrifuge. 

The  sputum  contains  extraneous  pigments  in  the  pneumonoconioses 
and  altered  blood-pigments  in  chronic  i)ulmonary  congestion. 


948 


GENERAL    LABORATORY    TECHNIC. 


Cursclinumn's  spirals  are  found  in  sputum  of  asthmatic  patients, 
and  appear  as  thick  white  bodies  having  a  twisted  tubular  form.  When 
examined  with  a  low  power,  they  show  a  central,  highly  refracting, 
twisting  thread,  around  which  is  a  meshwork  of  delicate  fibers.  They 
require  no  stain. 

Fibrinous  casts  are  tree-like  casts  of  the  terminal  bronchial  tubes, 
found  in  bronchitis  and  pneumonia,  and  composed  of  fibrin  or  mucin 
containing  entangled  cellular  elements.  (See  Fibrinous  Inflammations 
of  Mucous  Membranes.) 

Charcot-Leyden  Crystals. — These  crystals  are  colorless,  have  a  pointed 
octahedral  form,  and  are  found  chiefly  in  the  semi-solid,  grayish-yellow 
pellets  discharged  during  an  asthmatic  attack. 

The  diagnosis  of  pulmonary  cancer  from  neoplastic  fragments  found 
in  the  sputum  has  been  made  by  Cornil. 


Fig.  495.— Charcot-Levdex  Crystals.— (Laiidois.) 


Tubercle  Bacillus. — (For  technic  of  examination  see  article  on 
Bacteriology.) 

Bacillus  of  leprosy  occasionally  occurs  in  sputum.  (For  technic  of 
examination  see  article  on  Bacteriology.) 

Pnemnobacillus  (Friedlander),  Pneumococcus  (Frkrikel),  Actinomyces, 
Bacillus  anthracis,  staphylococci,  streptococci,  Bacillus  influenzce.  Bacillus 
mallei.  Bacillus  pestis,  Bacillus  typhosus,  etc.^ — (For  technic  of  demon- 
stration see  article  on  Bacteriology.) 

Fragments  of  echiuococcus  cysts,  the  scolices  or  hooklcts  of  the  para- 
site, the  eggs  of  the  Distoma  pulmonale,  rarely  the  parasite,  are  occasion- 
ally found  in  sputum.  The  Amoeba  histolytica  and  possibly  other 
amebae  are  occasionally  encountered;  Schmidt  has  observed  non- 
pathogenic flagellates  (trichomonads)  in  the  sputum. 

*  For  an  exhaustive  review  of  the  bacterial  flora  of  the  sptitum  see  Kerschen- 
steiner  ("Deut.  Arch.  f.  klin.  Med.,"  1902,  vol.  Ixxv) ;  Lenhartz  C"  Postgraduate," 
1Q02). 


INDEX. 


NDEX 


Abnormal,  5S 

Abrjn.  252 

Abscess,  amebic,  284 

cerebral,  870 

chronic  perinephric,  634 

cold.  Si  7 

of  muscle,  706 

hepatic,  749 

lingual,   679 

metastatic,  284 
ofheart,  495 
of  liver,  740 

myocardial,  495 

of  brain,  870 

of  liver,  740.  750 

of  lung,  592 

of  muscle,  703 

of  pharynx,  682 

paraosteal,  872 

perigastric,  703 

perinephric,  634 

periurethral,  559 

pharyngeal,  683 

pyemic.  275,  284 

of  liver,  750,  780 

splenic,  437 

thyroid,  780 

tonsillar.  681 

traumatic,  of  liver,  750 

tropic,  of  liver,  75  i 

wall  of,  295 
Acaridae.  212 
Acarinoses,  212 
Acarus  foUiculorum  hoininis,  213 

scabiei,  212 
Achondroplasia,  80  x,  802 
Achorion  Schonleinii,  1^4 
Acid-alcohol,  46 
Acid  glychiemalum,  47 

picric,  47 

rosolic,  as  an  indicator.  <)2o 
Acids  produced  by  bacteria,  86 
Acinous  adenoma.  318 
Acne  pancreatica,  774 
Acromegaly,  806 

Actinomyces,  demonstration  of,  167 
Actinomycosis,  166 

abdominal,  732 

of  bone,  819 

of  esophagus,  691 

of  heart,  503 

of  intestine,  732 

of  lar>-nx,  572 

of  liver,  761 


Actinomycosis  of  lung,  624 

of  mucous  membranes,  562 

of  muscle,  797 

of  spleen,  441 

of  tonsil,  682 

path  of  infection,  168 
Acute  aneurysm,  533 

ascending  paralysis,  882 

Bright's  disease,  643 

bulbar  paralysis.  869 

catarrh     of     mucous     membranes, 

547 
catarrhal  colitis,  722 

enteritis.  720 

morbid   anatnniv   >jf.    720 

gastritis,  700 

nephritis,  647 

pharyngitis,  682 

rhinitis.  565 

urethritis,  672 
desquamating  nephritis.  647 
diffuse  nephritis.  643.  647 

morbid  anatomy  of.   645 

splenitis,  434 
dilatation  of  heart,  517 

of  intestine,  707 
disseminated  tuberculosis  of  lung, 

engorgement  of  spleen,  434 
fatty  degeneration  of  liver,   747 

morV)id    anatomy   of, 
748 
fibrinous  bronchitis,  577 
focal  encephalitis,  simple,  867 
follicular  colitis,  723 
gastrectasis,  707 
gastric  catarrh,  700 

dilatation,  707 

morbid  anatomy  of.  707 
gastro-intestinal  dilatation,  707 
glanders,  161 

hemorrhagic  pancreatitis.  760 
hyperplasia  of  spleen,  434 
infectious  dysentery,  726 

epiphysitis,  81 1 

hepatitis.  740 

-    '  "  iry  angina.  '179 

inter  iritis,  641 

intestinal  707 

miliary  tu'  of  lung.  618 

nephritis,  urinary  changes  accom- 
panying. 648 
neuritis,  889 


95» 


952 


INDEX. 


Acute  nonsuppurative  hepatitis,  479 
interstitial  nephritis,  647 
thyroiditis,  780 
paralytic   distention    of    intestine, 

707.  715 
ileus,  707 
parenchymatous  hepatitis,  749 

nephritis,  646 
poisoning,  75 
polymyositis,  793 
reticular  lymphangitis,  538 
simple  endocarditis,  vegetations  in, 
508 
periostitis,  803 
serous  synovitis,  826 
suppurative  arthritis,  827 

interstitial  nephritis,  641 
lymphangitis,  538 
nephritis,  641 

morbid   anatomy   of,    642 
pancreatitis,  770 
periostitis,  803 
strumitis,  780 
tonsillitis,  681 

tuberculous  osteomyelitis,  817 
tubular  lymphangitis,  538 
yellow  atrophy  of  liver,  743,  747 
Addiment,  102 
Addison's  causeless  anemia,  422 

disease,  786 
Adenia,  simple,  448 

Adenitis  chronica  of  lymph-nodes,   444 
Adenoids,  post-nasal,  567 
Adenoma,  318 
acinous,  318 
malignant,  328 
of  cervix  uteri,  319 
of  nasal  mucous  membrane,  566 
of  pituitary  body,  878 
of  salivary  glands,  689 
of  suprarenals,  786 
of  thj-roid  gland,  783 
of  tonsil,  685 

papillary,  of  intestine,  734 
rectal,  319 
site  of,  318 
tubular,  318 
Adenosarcoma  of  kidney.  661 
Adhesions  of  pericardium,  467 
of  serous  membranes,  467 
Adiposis,  226 

dolorosa,  227 
Adiposity,  226 
Aerobe,  85 
Aerocele,  568 
Aeroscope,  Hesse's,  911 
Agar,  blood-smeared,  898 
Agate-ware  water-bath,  900 
Age,  66 
Agenesis,  223 
of  bone,  802 

of   pyramidal    motor    tract,    866 
Agents,  fixing,  33 
Agglutinable  substance,  104 
Agglutination,  104 


Agglutination  of    Bacillus  tuberculosis, 

147  . 
of  Bacillus  typhosus,  931 

of  Micrococcus  melitensis,  117 
Agglutinins,  104 

of  Spirillum  cholera  asiaticse,  143 
Agglutinophore  group,  104 
Agnathia,  674 

Air,   bacteriologic  examination  of,   913 
Air-passages,  infection  through,  92 
Albino,  236 
Albuminuria,  639 
Alcohol,  acid,  46 
Alexins,  99,  102 
Algor  mortis,  5 

Alimentary     canal.      See     Canal,     Ali- 
mentary. 
Alkali  produced  by  bacteria,  86 
Alveoli  of  carcinoma,  332 
Amboceptor,  102 
Ameba,  infection  of  colon  by,   724 

Mallory's  method   for  demonstrat- 
ing, 182 
Amebae,  181 
Amebiasis,  181 
Amitosis,  300 
Amitotic  division,  300 
Amoeba  buccalis,  181 

dysenteriae,  181 

gingivalis,  181 
Amygdalitis,  681 
Amyloid,  chemic  tests  for,  230 
Amyotrophy,  progressive  spinal,  788 
Anaematosis,  422 
Anaerobe,  85 
Anasarca,  270 
Anastomosis,  aneurysm  by,  346 

collateral,  260 
Anatomy  of  brain,  834 
Anemia,  259,  419 

Addison's  causeless,  422 

associated  lesions  of,  422 

blood  changes  in,  428 

effect  of,  259 

essential,  422 

ganglionic,  422 

idiopathic,  422 

local,  259 

myelogenic,  422 

of  bone,  805 

of  brain,  857 

of  esophagus,  690 

of  meninges,  850 

of  spinal  cord,  879 

of  thyroid  gland,  776 

pernicious,  422 

primar3^  419 

progressive  pernicious,  422 

secondary,  419 

conditions  in,  420 

splenic,  430,  438 
Anemias,    tabulation    of   blood-changes 

in,  428 
Anencephalia,  845 
Aneurysm,  531 


INDEX. 


953 


AiiLurysm.  acute,  533 
arteriovenous.  532 
by  anastomosis,  346 
chronic,  533 
circumscribed,  532 
cirsoid,  346 
cryptogenic.  53  i 
cure  of,  533 
cylindric,  532 
diffuse.  533 
dissecting.  533 
embolic.  533 
false,  531 
forms  of,  532 
fusiform,  532 
idiopathic.  533 
mycotic,  S62 
of  coronary  artery,  501 
of  heart.  501 

eld.  533 

racemose.  346 

recent.  533 

saccular.  532 

traumatic.  531 

true,  531 

verminous,  533 
Angina.  173,  682 

diphtheroid,  174,  685 

"angrenous.  557 

Ludwig's,  559,  679 

pectoris.  501 

pseudodiphtheric,  685 

submaxillary,  acute  infectious,  679 

Vincent's.  174 
Angioleucitis.  296,  53S 
Angioma  of  muscle,  797 

telangiectoides,  345 
Angiomata,  345 

of  brain,  877 

of  kidney,  661 

of  liver,  762 
Angiosarcoma,  plexiform,  359 
Angi(jsclerL>sis,  526,  535 
Anguillula  intestinalis,  204 

stercoralis,  204 
Anhydremia,  406 

Animals,     inoculated,     after-treatment 
of,  926 

inoculated,      postmortem      exami- 
nation upon,  926 
Ankyloglossia,  674 
Ankylosis,  false,  of  joints,  832 

of  joints.  832 

true,  832 
Ankylostomiasis,  205 
Anopheles,  186 
Anosmia,  567 
Anthracemia,  123 
Anthracosis,  232,  542 
Anthrax,  123 

cutaneous,  125 

erysij)elatous,  125 

intestinal,  125 

pulmonary,  125 
Anti-bodies,  og 


Anlil»(>tulm.  123 
Antislrepl()C(jIvsins.  116 
Antitoxin,  diphtheria.  121 

method  of  estimating  strength  of, 
926 

of  tetanus,  123 

of  plague,  131 
Antitoxins.  100 

meth<xl  of  preparing.  026 
Aorta,  abdominal  symmetric  aneurysm 
of.  532 

double,  487 

postmortem  examination  of,  20 
Aplasia,  223 
Apneumatosis,  587 
Apoplexy,  862 

cerebral,  264 

embolic,  862 

hemorrhagic,  862 

meningeal,  862 

of  pancreas,  768 

pulmonary.  5S5 

suprarenal.  7S5 

thrombotic,  862 
Apparatus  for  counting  colonies,  910 

Novy's.   for  anaerobic  cultivation. 
oi'7 
Appendicitis.  560 

catarrhal,  721 

chronic  catarrhal,  721 

gangrenous,  722 

perforative,  721 

propagative.  722 

suppurative.  72  i 

ulcerative.  721 
Appendix,  inflammations  of.  721 

concretions  within.  722 

cysts  of.  722 

gangrene  of.  722 

propagative.  of  infection.  722 
Apyrexia,  37 
Arachnoid,  833 
Argyria,  233,  236 
Arhinencephalia,  847 
Arnold's  steam  sterilizer.  005 
Arteries,  coronary,  aneurysm  of,  510 
atheroma  of,  501 
postmortem    examination    <>f. 

14 
obliterativc  arteritis  of,    501 

degenerations  of,  530 

diseases  of.  520 

hypertrophy  of,  533 

inflammation  of,  520 

structure  of,  520 

tuberculosis  of,  529 
Arterioliths,  277 
Arteriopathy,  cardiac,  5  1  ; 
Arteriosclerosis,  525 

intluencc  of.  on  nutnii'ii  ■>:  nr^Miis, 

?2S 

Arteritis.  520 

atheromatous,  520 
ectasia],  529 
infectiosa,  524 


954 


IXDEX. 


Arteritis  obliterans,  522 

obliterative,   of   coronary    arteries, 

501 
Artery,  pulmonary,  atresia  of,  487 
Arthritis,  acute  suppurative,  827 

chronic,  829 

fibrous  tuberculous,  8^  i 

deformans,  829 

drv,  829 

gouty,  828 

monarticular,  826 

polyarticular,  826 

purulent,  827 

rheumatoid,  829 

suppurative,  470 

trophic,  829 
Arthropathies,  neurogenous,  830 

spinal,  830 
Arthropodae,  212 
Arthrosis,  hydrops,  827 
Arthrospores,  formation  of,  82 
Ascarides,  202 
Ascaris  lumbricoides,  202 
Ascites,  270,  453,  520 

chyliform   454 

chylous,  265,  454,  537 
Ascococci,  106 
Aspergillosis,  162 
Aspergillus,  163 

fiavus,  163 

fumigatus,  163 

keratitis,  163 

niger,  163 
Asthma,  579 
Atavism,  61 
Ataxia,  Friedreich's,  887 

hereditary,  887 

locomotor,  886 
Atelectasis,  acquired,  587 

compression,  588 

congenital,  587 

obturation,  588 

pulmonary,  587 
Ateleiosis,  222 

asexual,  222 

sexual,  223 
Atheroma,  520 

of  coronary  arteries,  501 
Ath^-roidation,  779 
Athyroidea,  779 
Athyroidism,  779 
Athyrosis,  779 
Atony  of  bladder,  668 

of  intestine,  715 

of  stomach,  707 
Atresia  of  intestine,  714 

of  pulmonary  artery,  487 

of  stomach,  696 
Atrophy,  220 

active,  222 

acute  yellow,  of  liver,  743,  747 

brown,  of  heart,  488 

concentric,  of  bone,  809 

degeneration,  222 

eccentric,  of  bone,  809 


Atrophy,  general,  of  heart,  48S 

Haversian,  of  bone,  809 

local,  of  heart,  488 

lymphoid,  442 

mural,  of  bladder,  668 

neuropathic,  of  bone,  809 

numerical,  222 

of  bone,  809 

of  kidne^^  635 

of  liver,  742 

of  mucous  membranes,  542 

of  muscle,  788 

of  pancreas,  769 

of  perirenal  fat,  634 

of  spleen,  433 

of  suprarenals,  785 

of  thyroid,  777 

passive,  222 

pressure,  of  bone,  809 
of  liver,  743 

progressive     muscular,     of     spinal 
origin,  884 

red,  of  liver,  519,  740,  743 

senile,  of  bone,  809 
of  lung,  591 

simple,  222 

of  liver,  742 
Autoclav,  906 

Autoinoculation   of   tumors,   transcuta- 
neous, 314 
Auto-intoxications,  direct,  77,  376 

indirect,  376 
Axis-cvlinder  of  nerves,  835 


Bacillemia,  tuberculous,  154 

of  typhoid,  141 
Bacilli,  106 
Bacillus  aceticus,  86 

acidi  lactici,  86 

aerogenes  capsulatus,  135 

anthracis,  124 

botulinus,  123 

butyricus,  86 

coli  communis,  136,  137 

diphtheriae,  118 

metachromatic     granules     of 

119 
Neisser's  stain  for,  119 
polar  granules  of,  119 

dysenterife,  141 

fusiformis,  174 

influenzae,  126 

Koch-Weeks,  133 

lacunatis,  133,  134 

lepras,  157 

extracellular,  158 

mallei,  160 

oedematis  maligni,  136 

of  avian  tuberculosis,  147 

of  Friedlander,  127 

of  influenza,  toxins  of,  127 

of  sj'mptomatic  anthrax,    125,    126 

paratyphoid,  731 

pestis,  128 


INDICX 


95  5 


Bacillus  jjcstis,  toxins  of,  i  j(j 

pneumoniae,  127 

jiyoeyancus,  1,^4 

rhinoscleromatis,  150 

tetani,  121 

tuberculosis,  145 

agglutination  of,  1.(7 
paths  of  infection  by,  14.S 

typhi  abdoininalis,  i^c) 

typhosus,  131) 

ulceris  mollis,  132 
Bacteremia,  275,  377 
Bacteria,  81,  106 

aerobic,  85 

anaerobic,  85 

as  causes  of  disease.  Si,  04.  106 

chromogenic,  83 

in  osteomyelitis,  Sii 

in    tissue,     Weigcrt's    method    for 
demonstrating,  914 

liquefaction   of  gelatin  by,    84 

motility  of,  S2 

not  staining  by  Gram's  method,  84 

of  intestine,  720 

of  stomach,  607 

of  suppuration,  113 

pathogenic,  S3 

producing  hemolysins,  79 

propagation  of,  by  fission,  82 

reproduction  of,  82 

saprophytic,  83 

spore  formation  of,  82 

stain  reaction  of,  85 

staining  by  Gram's  method,   84 

structure  of,  81 

temporary  mounts  of,  913 

toxicogenic,  84,  88 

zymogenic,  8^ 
Bacteriolysis,  104 
Balantidium  coli,  182 
Banti's  disease,  439 
Barnes's  dropping  bottle,  46 
Basedow's  disease,  782 
Basket-cells  of  nervous  system,  841 
Basophilia,  410 
Battledore  hand,  806 
Bedbug,  213 

Beef  extract  for  preparing  bouillon,  901 
Beef-peptone-agar,  902 
Beef- peptone-gelatin,  901 
Bensley's  solution,  34 
Beri-beri,  890 
Bidcrmoma,  370 
Biebrich's  scarlet,  389 
Biermer's  disease,  422 
Bile-ducts,  763 

acute    catarrhal    inflammation    of, 

7  "3 
chronic  catarrhal  inflammation  of, 

7  ^'3 
cystadenomata  of,  766 
diseases  of,  763 
obstruction  to,  765 
papillomata  of,  766 
primary  cancer  of.  766 


Bile-ducts,  secondary  carcinoma  of,  766 

suppuration  of,  7^4 

tumors  of,  7 60 
Bilharzia  hicmatobia,  1(^3 
Bilharziosis,  193 
Biliary  cirrhosis,  75^ 

passages,  763 

postmortem    examination     of, 
18 
Birth-canal,  infection  through,  92 
Birth-mark,  345 
Black-leg,  126 
Black-tongue,  679 
Bladder,  atony  of,  668 

chronic  congestion  of,  66S 

encephaloid  carcinoma  of,  672 

exstrophy  of,  633 

hy])ertrophy  of,  669 

inflammation  of,  669 

malformations  of,  633 

mural  atrophy  of,  668 

papilloma  of.  671 

papilloma  fimbriatum  of,  671 

postmortem  examination  of,  16 

primary  sarcoma  of,  672 

scirrhous  carcinoma,  672 

tuberculosis  of,  670 

tuinors  of,  671 

villous  cancer  of,  671 
Blake  bottle  for  plating,  907 
Blastomyces,  170 
Blastomycosis,  170 
Bleeders,  263 
Bleichsucht,  421 
Blood,  385 

animal  parasites  in,  430 

changes  in  anemia,   tal»ulati"Ti  ••!' 
428 

coagulation  time  of,  404 

color  index,  398 

counting  erythrocytes,  399 
leukocytes,  402 

determination  of  specific  gravity  of. 

.,^07. 
diabetic,  staining  of,  381)        ^ 
differential  counting.  403 
examination  of,  385 
films,  staining  of,  386 
hemoglobin  estimation  of,  390 
infection  by  extension,  92 
in  pernicious  anemia,  422 
liquor  sanguinis,  405 
metastasis  of  tumors  by.  3 1 4 
method  of  obtaining  for  examina- 
tion, 3S5 
mycoses  of,  377,  430 
pathology  of,  405 
platelet.  417,  405 
staining  of,  386 

by  Ehrlich's  met  ii.Hi     ;>; 

by  Wright's  mcthcnl,  3S6 
volume  index  of,  404 

of  red  corpuscles.  403 
Blood-cells,  nucleated  red,  408 
Blood-scrum,  fluid.  S97 


956 


INDEX. 


Blood-serum,  human,  898 

mixture,  Loffler's,  898 

solid,  897 

sterilization  of,  897 

by  Councilman-Mallory  meth- 
od, 898 
Blood-vessels,  520 

amyloid  intiltration  of,   530 

angiosclerosis  of,  526,  535 

cryptogenic  calcification,  530 

diaphanous  degeneration  of,  530 

diseases  of,  520 

fatty  degeneration  of,  530 

hyaline  degeneration  of,  530 

of  heart,  malformation  of,  486 

ossification  of,  530 

terminal,  281 

tumors  of,  536 

vitreous  degeneration  of,    530 
Bodies,  foreign,  in  myocardium,  504 
in  stomach,  698 

loose,  in  joints,  826 

Pacchionian,  834 
Body  of  hernia,  713 

postmortem   external   examination 

of'  5 

internal  examination  of,  6 

restoration  of,  30 
Bone,  acquired  syphilis  of,  819 
actinomycosis  of,  819 
agenesis  of,  802 
anemia  of,  805 
angular  deformity  of,  820 
atrophy  of,  809 
caries  of,  812,  814 
chronic  infections  of,  817 

nonsuppurative    inflainniation 
of,  815 

tuberculosis  of,  8 1 7 
comminuted  fracture  of,  820 
compact  portion  of,  79S 
concentric  atrophy  of,  809 
congenital  syphilis  of,  818 
congestion  of,  805 
cysts  of,  825 
diseases  of,  798 
eccentric  atrophy  of,  809 
fibrous  union  of,  822 
fractures  of,  819 
glanders  of,  819 
greenstick  fracture  of,  820 
halisteresis  of,  810 
Haversian  atrophy  of,  809 
hyperemia  of,  805 
hypertrophy  of,  806 
immediate    complications    of   frac- 
ture of,  820 
inflammations  of,  810 
leontiasis.  807 
leprosy  of,  819 
line  of  fracture,  820 
malformation  of,  801 
necrosis  of,  812 
neuropathic  atrophy  of,  809 
postmortem  examination  of,    26 


Bone,  pressure  atrophy  of,  809 

regeneration  of,  814 

repair  of,  820 

resorption  of,  800 

rotary  deformity  of,  820 

secondary    complications    of    frac- 
ture of,  820 

senile  atrophy  of,  809 

spongy  layer  of,  798 

structure  of,  798 

syphilis  of,  818 

toxic  necrosis  of,  813 

tuberculosis  of,  817 

tumors  of,  823 
Bone-cutting  forceps,  29 
Bone-marrow,  799 

cells  of,  799 

changes  in,  802 

human,  elements  of,  800 

red,  799 

yellow,  800 
Botulism,  123 
Bouillon,  Koch's  alkaline  beef-peptone, 

900 
Brain,  834 

abscess  of,  870 

active  hyperemia  of,  857 

acute  inflammations  of,  866 

anatomy  of,  834 

anemia  of,  857 

angiomata  of,  877 

cholesteomata  of,  877 

circulatory  disturbances  of,  857 

cysts  of,  877 

diseases  of  blood-vessels  of,  864 

edema  of,  850 

ependymal  sclerosis,  874 

fibromata  of,  877 

gliosarcoma,  876 

granular    ependymal    sclerosis    of, 

874 

heterotopia  of  gray  matter  of,  847 

hypertrophy  of,   847 

inflammation  of,  866 

insular  sclerosis  of,  873 

lipomata  of,  877 

lobar  sclerosis  of,  874 

malformations  of,  845 

multiple  sclerosis  of,  873 

occlusion  of  vessels  of,  864 

osteomata  of,  877 

parasitic  cysts  of,  877 

partial  hypoplasia  of,  847 

passive  hyperemia  of,  858 

Pitres-Nothnagel  method  of  exam- 
ining, 25 

postmortem  examination  of,  22 
method  of  preserving,  24 
removal  of,  22 

primary  carcinoma  of,  877 

psammoma  of,  877 

red  softening  of,  865 

sarcomata  of,  876 

smooth  ependymal  sclerosis  of,  874 

softenina:  of,  86=; 


i.\i)i:x 


957 


Brain,  syphilis  of,  872 

thn)inl)osis  of  veins  of,  SOO 
tuberculosis  of,  S;  ^ 
tumors  of,  875 
vesicles,  842 
white  softcnini^  of,  865 
vellow  softening  of,  865 
Bright  s  disease,  acute,  643 

chronic,  see  chronic  ditTuse  ne- 
phritis, 648 
forms  of,  640 
Bronchi,  575 

chronic  lil)rinous  inflammation  of, 

5  7-^ 

concretions  of,  5 So 

fibrinous  inflammations  of,  577 

gangrcn<nis  intl.ammations  of,  578 

hemorrhai^e  irnm,  575 

hemorrhagic  intlammations  of,  578 

hyjicreniia  of,  575 

inflammation  of  capillary,  607 

malformations  of,  575 

normal  structure  of,  575 

parasites  in,  627 

])igmentary  infiltration  of,  578 

postmortem  examination  of,  15 

pseudomembranous  inflammations 
of.  577 

stenosis  of,  578 

syphilitic  inflammation  of,  578 

tufjerculosis  of,  578 

tumors  of,  580 
Bronchiectasis.  57Q 
Bronchiolectasis,  570 
Bronchioles,  inflammation  of,  577 
Bronchioliths,  580 
Bronchiolitis,  577 
Bronchitis,  capillary,  607 

catarrhal,  575 

chronic  caseous,  578 
catarrhal,  577 
fibrinous,  578 

fetid,  576 

fibrinous,  577 

follicular,  576 

gangrenous,  578 

hemorrhagic,  578 

pseudomembranous   inflammations 

of.  577 

putrid,  576 

syf)hilitic,  578 
Bronchoblcnorrhea,  576 
Bronchocele,  780 
Bronchopneumonia,  606 

causes  of,  607 

complications  of,  61 1 

morl)id  anatomy  of,  60S 
histology  of,  ftog 

terminations  of,  610 
Bronchorrhea,  576 
Brush  for  handling  sections,  43 
Bubo,  444 

chancroidal,  132 

parotid,  f)S6 

primary,  130 


Bubo,  primary,  of  first  order,  130 
of  second  order,  130 
secondary,  130 
Buerger's  method  for  staining  capsules, 

Burns  as  causes  of  di.scase,  70 

classified  as  to  degree,  7  i 

systematic  i)henomena  of,  71 
Bursa,  inflammation  of,  456 

suppuration  of,  470 
Bursitis,  456 

sujiinirativc,  470 


Cachexia  strumii)riva,  770 
Calcilii  ation,  cry])logenic,  of  blood-ves- 
sels, 530 

miliary,  238 

of  l)lood-vessels,  521) 

of  pericardium,  468 
Calculi,  biliary,  765 

in  stomach,  6g8 

mulberry,  670 

of  intestine,  736 

pancreatic,  773 

urinary,  670 

vesical,  670 
Callus,  822 

Calvarium,  postmortem  examination.  22 
Canal,  alimentary,  673 

central,  of  cord,  842 
Cancer  (also  see   Carcinoma),   acinous, 
332 

acute,  335 

adenoid,  328 

chronic,  332 

ectopic  thyroid,  776 

gangrenous,  of  stomach,  700 

gastric,  morbid  anatomy  of,  7o<) 

hard.  332 

infra-ampullary,  735 

juxtaicjunal,  735 

medullary,  335 

melanotic,  324 

of  larynx,  574 

extrinsic,  574 
intrinsic,  574 

of  stomach,  701) 

of  suprarenals,  7.S6 

of  thyroid,  7S3 

])eri-ampullary,  735 

primary,  of  bile-ducts,  766 
of  liver,  761 
of  lung,  625 

secondary,  of  muscles,  797 

^olt,  335' 

superficial,  325 

supra-ampullary,  735 

varieties  of.  325 

villous,  of  bladder,  671 
Cancrum  oris,  256,  558,  676 
Capacity,  measures  of,  2 
Capsulitis,  circumscribed,  of  spleen.  436 

fibrous.  47 ^ 

hepatic.  758 


958 


INDEX. 


Carbol-hichsin,  Ziehl's,  49 
Carcinoma,  322 

alveoli  of,  332 

atrophic  scirrhous,  334 

basocellulare,  331 

branchiogenic,  674 

clinical  characters  of,  323 

colloid,  336 

degeneration  of,  324 

cystic,  331 

site  of,  331 
styloid,  331 

diagnostic  features  of,  362 

encephaloid,  335 
of  bladder,  672 

endothelial,  359 

epithelial,  325 

fibrous,  332 

gelatiniform,  336 

glandular,  325 

varieties  of,  332 

juxta-pyloric  duodenal,  735 

melanosis  of,  324 

melanotic,  337 

mucoid,  336 

myxomatous  degeneration  of,   324 

of  bile-ducts,  766 

of  brain,  877 

of  esophagus,  693 

of  intestine,  734 

of  lung,  626 

of  lymph-nodes,  449 

of  nose,  566 

of  stomach,  709 

pigmentation  of,  324 

scirrhous,  332 

forms  of  degeneration  in,  334 
of  bladder,  672 

secondary  changes,  324 

site  of,  325 

varieties  of,  325 

villous,  of  bladder,  671 
Carcinomatosis  cutis,  357 

of  serous  membranes,  481 
Carcinosarcomata  of  thyroid,  783 
Cardiopathy,  515 
Cardioptosis,  485 
Cardiospasm,  691 
Caries,  dry,  814 

humida,  814 

of  bone,  812,  814 

sicca,  814 
Carmin,  45 

Carnification  of  lung,  588 
Caseation,  254 
Casts,  blood,  640 

epithelial,  640 

fatty,  640 

fibrinous,  in  sputum,  948 

granular,  640 

hyaline,  640 

renal,  639 

waxy,  640 
Catarrh,  acute  gastric,  700 

chronic  gastric,  701 


Catarrh,  chronic  nasal,  565 
pharyngeal,  682 

dry,  of  mucous  membranes,  550 

suffocative  bronchial,  576 

suppurative,      of     mucous      mem- 
branes, 559 
Causes,  autogenous,  66 

conditional,  66 

exciting,  66 

exogenous,  67 

external,  67 

extrinsic,  67 

immediate,  66 

internal,  66 

intrinsic,  66 

of  malformation,  61 

mental,  68 

predisposing,  66 

remote,  66 

unconditional,  66 
Cavity,  abdominal,  postmortem  exami- 
nation of,  9 

bronchiectatic,  579 

thoracic,  postmortem  examination 
of,  9 
Cecitis,  720 
Cell,  direct  division  of,  300 

division  by  force,  301 

gangUon,  835 

bipolar,  835 
multipolar,  835 
pathology  of,  858 
unipolar,  835 

indifferent,  302 

indirect  division  of,  300 

parasitism  of,  in  neoplasms,  312 

reproduction,  300 
Celloidin,  infiltration  with,  42 
Cellulitis,  diffuse  submaxillary,  679 

suppurative,  296 
Center,  thermotactic,  373 
Cercomonas  hominis,  182 
Cerebral  abscess,  wall  of,  870 

apoplexy,  862 

hemorrhage,  862 

softening,  864 
Cerebritis,  866 

acute  hemorrhagic,  868 

suppurative,  869 
Cerebrospinal  meningitis,  855 
Cerebrum,  834 

Cervix  uteri,  adenoma  of,  319 
Cestodes,  194 
Chalicosis,  232 
Chancre,  hard,  177 
Chancroid,  132 
Charbon,  124 

symptomatique,  126 
Charcot-Leyden  crystals  in  sputum,  948 
Charcot's  disease  of  joints,  830 
Chemiotaxis,  291 
Chemotaxis,  291 
Chills,  378 

Chloral,  aqueous  solution  of,  for  preser- 
vation, 32 


INDEX. 


959 


Chlorancniia,  421 
Chloremici,  421 
Chloruformbacillinc.  SS 
Chlorolyniphoma,  j6o 
Chloroma,  3O0 
Chlorosis,  421 

associated  lesions  of,  422 
Cholangitis.  550,  763 

acute  catarrhal,  763 
chronic  catarrhal,  763 
suppurative,  7  64 
Cholecystitis.  550 
fibrinous,  764 
phlegmonous,  764 
pseudomembranous,  764 
tuberculous,  764 
Cholelithiasis,  765 
Cholera  asiatica,  142.  727 

infantum,  723 
Cholesteatoma,  358 
Cholesteomata  of  brain,  877 
Chondritis,  articular,  826 
Chondroblasts,  821 
Chondroma.  339 
laryngeal.  575 
of  heart.  503 
of  muscle.  797 
of  thyroid,  783 
Chondrosarcoma,  361 
Chorioepithelioma,  364 
Chromatolysis,  779,  859 
Chromo-aceto-osmic  acid  mixture,  33 
Chromogens,  83 
Chronic  aneurysm,  533 

anterior  poliomyelitis,  884 

arthritis,  829 

caseous  peribronchitis,  578 

tuberculosis  of  bowel,  732 
of  joints,  831 
catarrhal  appendicitis,  721 
bronchitis,  577 
colitis,  724 
enteritis,  720 
gastritis,  701 

inflammation  of  mucous  mem- 
branes, 546,  548 
congestion  of  liv'er,  740 
cyanosis,    with    polycythemia    and 

enlarged  spleen,  411 
desquamative  nephritis,  648 
diffuse  nephritis,  648 

splenitis,  435 
dilatation  of  stomach,  708 
edema  of  larynx.  573 
epithelial  nephritis,  648 
glanders,  161 

hyperplastic  inflammation  of  serous 
membranes,  473 
tuberculosis.  153 

of  intestine,  733 
of     mucous     membranes, 
561 
infectious  inflammations  of  mucous 

membranes,  5O0 
interacinar  pancreatitis.  772 


Chronic  interlobular  pancreatitis,  772 
internal  pachymeningitis,  849 
interstitial  hepatitis,  753 

nephritis,  O52 

pancreatitis,  772 

parotitis.  086 

pneumonia,  611 

thyroiditis,  780 

tonsillitis,  682 
lacunar  tonsillitis,  68  2 
laryngitis,  569 

lead  intoxication,  neuritis  of,  891 
leptomeningitis,  850 
lymphangitis,  538 
meningo-encephalitis,  870 
nephritis,  648 
neuritis,  889 
pancreatitis,  771 
parenchymatous  nephritis,  648 
periadenitis,  444 
peribronchitis,  577 
pharyngeal  catarrh,  682 
pharyngitis,  682 
phlebitis,  535 
pneumonia,  604 
poisoning,  75 
poliomyelitis,  884 

productive  inflammation  of  serous 
membranes,  473 

osteitis,  815 

periostitis,  805 
rhinitis.  365 
serofibrinous    exudative     serositis, 

473 

serositis,  472 

serous  exudative  serositis,  473 

splenic  tumor,  435 

tonsillitis,  681 

tubular  nephritis,  648 
Chylangioma,  347 
Chyle-cysts,  537 
Chylocele,  210,  537 
Chylothorax,  265 
Chyluria,  210,  537 
Cimex  hirundinis,  213 

lectularia,  213 
Cirrhosis  anthracotica  of  liver,  756 

atrophic,  of  liver,  753 

biliary,  of  liver,  757 

congestion  of,  519 

fatty,  of  liver,  756 

hypertrophic  biliary,  of  liver,  757 

interlobular,  of  liver,  755 

intralobular,  of  liver,  755 

Laennec's,  of  liver,  753 

monolobular,  of  liver,  755 

obstructive  biliary,  756 

of  collapse  of  lung,  588 

of  liver,  753 

perilobular,  of  liver,  755.  758 

polylobular,  of  liver,  755 

portal,  753 

pulmonary,  61 1 

true,  of  lung,  613 

venous,  of  liver,  753 


960 


INDEX. 


Clarke,  column  of,  841 

Classification  of  tumors,  315 

Cleaning  of  hemocytometer,  402 

Clearing  agents,  35',  45 

Clots,  postmortem,  270 

Cloudy  swelling,  241 

Coagulation  of  milk  by  bacteria,  84 

necrosis,  251 
Coagulometer,  Wright's,  405 
Cocci,  106 

pathogenic,  107 

varieties  of,  106 
Coccidia,  184,  370 
Coccidiosis,  184 
Coccidium  oviforme,  185 
Cold,  72 
Colitis,  550,  720,  722 

acute  catarrhal,  722 
follicular,  723 

chronic  catarrhal,  724 

croupous,  724 

cystic,  724 

diphtheric,  725 

gangrenous,  725 

mucous,  725 

necrosing,  725 

poh-posa,  724 

pseudomembranous,  724 
Collapse  of  lung,  587 
Colloid,  246 
Colon,  acquired  dilatation  of,  715 

chronic  catarrh  of,  724 

gangrene  of,  725 

infection  by  ameba,  724 

inflammation  of,  722 

invagination  of,  717 
Colonies,  apparatus  for  counting,  910 
Color  index  of  blood-cell,  398 
Colpitis  mycotica,  165 
Column  of  Clarke,  841 
Complement,  102 
Complications,  65 

immediate,  of  fracture  of  bone,  820 

of  bronchopneumonia,  611 

secondary,  of  fracture  of  bone,  820 
Compound  granule  cells,  865 
Concretions  of  bronchi,  580 

within  appendix,  722 
Conditions,  elephantoid,  537 
Congestion,  265 

active,  260 

chronic,  of  liver,  740 
of  bladder,  668 

cirrhosis  of,  519 

hypostatic,  266 
of  lung,  582 

morbid  anatomy  of,  266 

of  bone,  805 

of  esophagus,  690 

of  intestine,  719 

of  kidney,  637 

of  larynx,  569 

of  lung,  582 

of  mucous  membranes,  541 

of  pancreas,  768 


Congestion  of  regurgitation,  266 
of  stomach,  698 
of  thyroid,  776 
passive,  265 

of  spleen,  436 
venous,  265 
Congo  red,  389 
Conidia,  162 
Conjunctivitis,  133 
Constitution,  lymphatic,  451 
Constriction,  subvalvular,  of  heart,  516 
Continuity,   extension   of  infection   by, 

92 
Conus  arteriosus,  stenosis  of,  487 

medullaris,  834 
Copremia,  376 
Copula,  102,  184 
Cor  hirsutum,  462 
villosum,  462 
Coronary  arteries,  atheroma  of,  501 

obliteration  of,  501 
Corpora  amylacea,  865,  875 
Costotome,  9 
Cover-glass  forceps,  912 
Coxalgia,  817 
Craniopagus  frontalis,  63 
occipitalis,  63 
parietalis,  63 
Craniorrachischisis  totalis,  842 
Cranioschisis,  845 
Craniotabes,  823 
Crenation,  408 
Cretinism,  sporadic,  777 
Crisis,  379 

Croup,  catarrhal,  569 
false,  569 
membranous,  569 
spasmodic,  569 
Croupous  pneumonia,  597 

abscess  of  frontal  sinus  in,  606 
accompanied  by  endocarditis, 

605 
accompanied  by  pleurisy,  605 
blood-changes  in,  605 
causes  of,  598 
complications  of,  605 
engorgement,  600 
gray  hepatization,  603 
meningitis  in,  606 
monarticular   joint    inflamma- 
tion in,  606 
morbid  anatomy  of,  599 
nephritis  in,  606" 
pericardial     inflammation     in, 

605 
red  hepatization,  600 
suppurative  parotitis  in,   606 
terminations  of,  603 
Culex,  214 

Culture-containers,  903 
Culture-media,  897 
artificial,  897 
natural,  897 
Cultures,  anaerobic,  917 
hanging-drop,  918 


INDi;  X. 


961 


Cultures.  iiuul)atii>n  of,  ()22 

mixed,  uoO 

pure,  iSgy 

shako,  ()i  7 

slant.  1)05 

smear,  008 

stab,  008 

stroke,  ()oS 
Culture-tulie.  Sternberg's  anaerobic,  Q17 
Cure  of  aneurysm.  53^ 
Curschmann's  spirals  m  sputum,  047 
Cyanosis,    chronie,    with    polycythemia 

and  enlari,'ed  sjileen,  41  1 
Cyclocephalia,  S47 
Cyclopia,  564,  847 
Cylindrolysis,  640 
Cylindroma.  360 
Cyst  adenoma.  3f>8 

papillary,  of  thyroid,  7S3 
Cystadenomata  of  bile-ducts,  766 

of  pancreas,  774 
Cysticercosis,  107 
Cysticercus  cellulosie,  i()7,  370 

saginata,  106 
Cystitis,  550,  66q 
Cystocele,  abdominal,  668 

vaginal.  668 
Cystoma.  36S 

of  pancreas,  774 
Cysts.  367 

branchial,  674 

cavernous,  367 

chylous,  347 

coccidial,  184 

conglomerate  renal,  665 

dermoid,  360 

of  thyroid,  784 

extravasation,  369 

exudation,  367 

hydatid,  loq,  370 
of  heart,  503 
f>f  kidney,  665 

metastatic,  of  spleen,  440 

inultilocular,  367 

multiple,  367 

mucous,  367 

nephric,  367 

of  appendix,  722 

of  bone,  825 

of  brain,  877 

of  kidney,  663 

of  liver,  762 

of  pancreas,  773 

of  pia-arachnoid,  857 

of  spinal  cord,  888 

of  spleen,  773 

of  suprarenais,  786 

of  thyroid,  784 

of  urachus,  633 

papillifcrous,  3(17 

paranephric  urinary,  634 

pararenal,  634 

parasitic,  370 

of  brain.  877 

proliferous,  367 
62 


Cysts,  psoudopancreatic,  774 

retention,  307 

retrojK-ritoncal,  480,  735 

siinguineous,  30^ 

simj)lc,  367 

thyroglossal,  776 

traumatic  jjancrcatic,  774 

unilocular,  367 

urinosanguineous,  634 
Cytase,  102 

Cytodiagnosis,  2f)i.  477 
Cytolysis,  Ssg 
Cytoryctes  variola*,  186 


Dare's  hemoglobinometer,  3<;5 
Dcaih,  thymic.  451 
Ucath-point.  thermal,  020 

for  bacteria.  85 
Deciduoma  malignum,  364 
Decolorization  of  thrombus,  276 
Deformity,  60 

angular,  of  bone,  820 
ape-like,  806 
rotary,  of  bone,  S20 
Degeneration,  240 

acute  fatty,  of  liver,  747 
ascending,  of  spinal  cord,  87(j 
chronic  renal,  640 
colloid,  246 

of  carcinoma.  324 
corneous,  248 
cystic,  of  kidney,  665 
diaphanous,  of  blood-vessels,  530 
fatty,  242 

demonstration  of,  244 

of  blood-vessels,  530 

of  joints,  8 25 

of  mucous  membranes.  545 

of  muscle,  701 
fibrous,  of  myocardium,  405 
glassy.  247 
granular,  241 

of  heart.  4()  1 

of  mucous  mcmt'r.incs.  545 

of  muscle,  7QI 
hyaline,  247 

of  blood-vessels,  530 

of  heart,  493 

of  joints,  825 

of  lymph-nodes.  443 

of  muscle,  791 
hydropic,  245 

demonstration  oi,  ^40 

nf  muscle.  7QI 
keratohyaline,  24S 
mucoid,  246 

of  joints,  S25 
myxomatous,  246 

of  carcinoma,  324 
of  bl<xxl -vessels,  530 
of  gastric  muco.sa.  700 
of  kidnty.  636 
of  lip<j>ma,  339 


962 


INDEX. 


Degeneration  of  nerves,  889 

of  nerve-cell,  demonstration,  853 

of  pericardium,  456 

of  suprarenals,  785 

of  thyroid,  779 

parenchymatous,  241 

demonstration  of,  242 

of  liver,  747 

of  suprarenals,  785 

secondary,  of  nerve-hbers,  860 
of  spinal  cord,  882 

vitreous,  247 

Vjlood-vessels  of,  530 

Wallcrian,  861 
Degenerations  and  infiltrations,  224 
Delafield's  hematoxylin,  46 
Demarcation,  line  of,  257 
Dementia  paralytica,  871 
Demodex,  213 
Dendrites,  changes  in,  859 

of  nerves,  836 
Deposits,  calcific,  demonstration  of,  238 

uric  acid,  238 
Dermatitis,  blastomycetic,  171 
Dermatolysis,  342 
Dermatomycosis,  163 
Dermatomyositis,  793 
Dermoids,  compound,  370 

simple,  370 

traumatic,  370 
Descensus  ventriculi,  697 
Desmoid,  341 
Desmon,  102 
Dexiocardia,  484 
Diastematomyelia,  845 
Diathesis,  inherited  hemorrhagic,  262 
Dibothriocephalus  latus,  201 
Dicephalus,  63 
Dicrocaelium  lanceatum,  192 
Differentiation  of  stain,  45,  49 
Digitu  mortui,  257 
Dilatation,  acquired,  of  colon,  715 
of  esophagus,  692 
of  intestine,  715 

acute  gastric,  707 

gastro-intestinal,  707 
intestinal,  707 
of  heart,  517 

ampullary,  of  veins,  536 

atonic,  of  esophagus,  692 

chronic,  of  heart,  518 

c^^stic,  of  veins,  534 

of  esophagus,  diffuse,  692 

of  heart,  with  thickening,  515 
with  thinning,  515 

of  intestine,  715 

of  stomach,  706 

morbid  anatomy  of,  707 

varicose,  of  veins,  536 
Diphtheria,  684 

antitoxin,  121 

bacillus  of,  118 

chronic,  684 

clinical,  684 
Diphtheriolysin,  120 


Diphtheromycosis,  684 

Diplococci,  106 

Diplococcus  pneumoniae,  109,  598 

demonstration  of,  no 

pathogenesis  of,  no 

staining  of,  in  tissues,  no 
intracellularis  meningitidis,  in 

demonstration     of,      in, 
856 
rheumaticus,  112 

pathogenesis  of,  113 
Dipygus,  63 
Disease,  64 
acute,  65 

Bright's,  643 
Addison's,  786 
albuminoid,  227 

alterations    in    atmospheric    pres- 
sure as  causes  of,  73 
animal  parasites  as  causes  of,   iSi 
arthropathic,  831 
bacteria  as  causes  of,  106 
Banti's,  439 
Basedow's,  782 
Biermer's,  422 
Bilharzia,  193 
caisson,  73 
causes  of,  66 
Charcot's,  of  joints,  830 
chronic,  65 
communicable,  65 
congenital  cystic,  of  pancreas,   774 
electric  discharges  as  causes  of,  74 
foot  and  mouth,  675 
functional,  64 
Glenard's,  431 
guinea-worm,  210 
Hodgkin's,  430,  447 
ingestive,  65 
Kahler's,  824 
lardaceous,  228,  490 

of  heart,  490 

of  liver,  745 

of  lymph-nodes,  443 

of  spleen,  434 

of  suprarenals,  785 
Madura,  organism  of,  169 
Mikuhcz's,  186 
organic,  64 

poisons  as  causes  of,  75 
Pott's,  817,  830 
Raynaud's,  257 
Riga's,  679 

scalds  and  burns  as  causes  of,    70 
screw- worm,  214 
specific,  65 

starvation  as  a  cause  of,  68 
thermal  causes  of,  70 
trauma  as  a  cause  of,  72 
villous,  317 
wool-sorter's,  124 
Diseases,  bacterial,  65 
contagious,  65 
chronic,  65 
communicable,  and  insects,  214 


INDKX. 


0^3 


Diseases,  cryptogenic,  65 

clephantuid,  210 

endemic,  h^ 

epidemic,  05 

foudrovant,  65 

fulminating,  65 

germ.  05 

hyperacute,  65 

idiopathic,  65 

infectious,  63 

intercurrent,  O; 

medical,  of  kidney,  035 

microhic,  65 

neuropathic,  of  joints,  830 

of     blood-vessels     supjjlying     the 
heart,  501 

of  kidney,  634 

of  kidney-bed,  634 

of  larger  blood-vessels  of  cranium, 
878 

of  pineal  gland,  878 

of  pituitary  body,  877 

of  urinary  organs,  628 

pandemic,  65 

parasitic,  65 

sporadic,  65 

surgical,  of  kidney,  635 

traumatic.  65 
Dish,  I^etri,  go7 
Disinfection,  021 

technic  of,  922 
Dissecting  forceps,  20 
Disseminated  pneumonia,  607 
Distention,  renal,  665 
Distoma  hepaticum.  192 

hematobium,  194 

in  urine,  194,  937 

lanceolatum,  i<)2 

pulmonale.  192 

ringeri.  192 

sibiriscum.  192 

Westcrmanni,  192 
Distomatosis,  192 

Bilharzia,  193 

hepatic,  192 

intestinal,  193 

pancreatic,  193 

pulmonary,  192 

venal,  193 

of  intestine,  735 
Distomiasis,  see  Distomatosis,  102 
Disturbances,  circulatorv,  259 
Disuse  as  a  cause  of  atrophy,   220 
Diverticula,  esophageal,  692 

false,  7 1 5 

gastric,  696 

intestinal,  714 

Meckel's,  714 

of  esophagus,  692 

pulsion,  of  esophagus,  6q2 

traction,  of  esophagus.  692 

tract ion-pulsion,  of  esophagus,  693 
Diverticulitis,  715 
Division,  amitotic,  300 

mitotic,  300 


Dourine,  183 
Dracontiasis,  210 
Dracunculus  Medinensis,  210 
Dropsy.      See  lidcina. 
cellular,  245 
of  gall-bladder,  663 
of  joints,  827 
of  serous  cavities,  453 
Duckwall's  Hagella-stain,  915 
Duct,  thyroglossal,  776 
Ductus  arteriosus,  patulous,  487 
Dunham's  peptone  solution,  ^)o(^ 
Duodenitis,  720 
Duodenum,     postmortem    examination 

of,  18 
Duplicitas  anterior,  63 
parallela,  63 
posterior,  63 
Dura  mater,  833 

circulatorv     disturbances     of, 

848 
hyperemia  of,  848 
syphilis  of,  849 
tuberculosis  of,  849 
tumors  of,  849 
Durante-Cohnheim,     inclusion     theory 

of,  310 
Dyes,  anilin,  used  in  staining,  48 
Dysentery,  141,  725 

acute  infectious,  726 
amebic,  726 
Dyspepsia,  550 

Dystrophy,  progressive  muscular,  789 
Erb  type,  790 
facioscapulohumeral  type, 

790 
Landouzy    and     Dejerine 
type,  790 


Ecchondromata,  339 
Ecchymosis,  6,  264 
Echinococcus  altriciparicns.  i()o 

granulosus,  199 

hominis,  199 

hydatidosus,  199 

multilocularis,  199 

scolices  of,  200 

scolipariens,  i<>(} 

veterinorum,  199 
Ectasia,  arterial,  531 
Ectasy,  gastric,  706 
Ectopia,  sS 

cordis,  4S4 

vesicae,  633 
Edema,  267 

acute  fulminating  pulmonary,  5 S3 

angiosclerotic.  270 

cachectic.  269 

cardiac,  520 

cerebral,  270 

chronic,  of  larynx,  573 

chronic,  pulmonary,  584 

ex  vacuo,  269 

infectious.  269 


964 


INDEX. 


Edema,  inflammatory,  269 

ischemic,  26Q 

morbid  anatomy  of,  269 

neuropathic,  269 

of  brain,  850 

of  glottis,  573 

localized  pulmonary,  584 

phlegmonous,  of  larynx,  573 

pulmonary,  583 

simple  acute,  583 

serovis,  of  larynx,  573 

thermal,  269 

traumatic,  269 

trophic,  269 

toxic,  269 

varieties  of,  269 
Egg  for  use  as  culture-medium,  899 

sterilization  of,  for  culture-medium, 
899 
Ehrlich's  acid  hematoxylin,  47 

stain  for  blood,  388 
Elements  of  human  bone-marrow,   800 
Elephantiasis,  209,  537 
Emboli,  forms  of,  279 

infective,  284 

neoplastic,  284 

retrograde,  279 
Embolism,  278 

of  coronary  arteries,  501 

pulmonary,  585 

recurrent,  279 
Embolus,  278 

changes  indtxced  by,  279 

crossed,  279 

infective,  279 

paradoxic,  278 

simple,  279 
Embryoinata,  370 
Emphysema,  acute  vesicular,  592 

atrophic,  591 

cadaverosum,  135 

compensatory,  589 

gangrenous,  257 

gaseous,  134 

hypertrophic,  589 

idiopathic,  589 

interlobular.  588 

interstitial,  588 

large-lunged,  589 

local,  589 

of  lung,  588 

of  neck,  568 

of  spleen,  431 

senile,  591 

small-lunged,  591 

substantial,  589 

vesicular,  589 

vicarious,  589 
Empyema,  469 

bacteriology  of,  469 

interlobar,  471 

of  gall-bladder,  764 
Encephalitis,  acute,  866 

hemorrhagic,  876 
suppurative,  867 


Encephalitis,  chronic,  870 
meningo-,  870 

hematogenous,  867 
Encephalocele,  846 
Encephalomeningocele,  846 
Encephalomyelitis  ha^morrhagica,  868 
Enchondroma,  339 
Enchondrosis,  339 
Endarteritis,  atheromatous,  520 

cartilaginosa,  525 

chronica  nodosa,  520 

deformans,  520 

luetica,  529 

tuberculosa,  154,  529 

verrucosa,  525 

warty,  525 
Endocarditis,  504 

acute  malignant,  510 
simple,  506 

bacteria  in,  508 
vegetations  in,  508 

adhesive,  512 

bacterial,  510 

chronic,  512 

ulcerating,  512 

classification  of  forms,  504 

diphtheritic,  510 

fibrous,  512 

forms  of,  505 

in  croupous  pneumonia,  605 

indurative,  512 

interstitial,  512 

malignant,  505 

mural,  505 

mycotic,  510 

permanent,  512 

polypous,  509 

pustular,  510 

pyemica,  510 

sclerotic,  512 

simple,  505 

ulcerative,  510 

valvular,  505 

verrucosa,  509 

villous,  509 
Endocardium,  inflammations  of,  504 

structure  of,  504 
Endometritis,  septic,  559 
Endoneurium,  St,^,  841 
Endophlebitis  tuberculosa,   154 
Endospore  fonnation  of  bacteria,  82 
Endothelioma.  358 
Endotheliomata,  hemangio-,  359 

lyinphangio-,  359 

of  pia-arachnoid,  856 

of  pituitary  body,  878 

of  salivary  glands,  689 

of  serous  membranes,  480 
Endotoxin,  88,  97.  120 
Engorgement,  acute,  of  spleen,  434 

splenic,  434 
Enlargement,  inflammatory.  299 
Enostoses,  340,  808 
Entamoeba  coli,  181 

histolvtica,  181 


I  M )  I'.  X  . 


'>'>5 


liiUtTii.-  it-'vcr.  7J.S 
ICntcritis,  720 

acute  (.iitarrhul.  720 

(.hronic  catarrhal,  720 

fi)llicul;ir.  720 

j^angrcnous,  72  i 

licinorrhaijic.  72  1 

pliloijnionoiis,  72  1 

psouiloniembrarums,  72  t 

sortms.  720 
EnttTocelc,  7  13 
Enterocolitis,  720 
Entcrocystoma.  7  1 4 
Entero-epiplocele,  713 
Entcrolithiasis,  735 
Enteroliths,  730 
Enteroplegia,  707,  715 
Enteroptosis,  431,  712 
Enterorrhagia,  264 
Enterosepsis,  376 
Enterotome,  iS 
Enzymes,  86 
Eosin,  alcoholic  solution  of.  47,  50 

aqueous  solution  of.  50 
Eosinophilia,  2Q2 
Epidermoids.  370 
Epineurium.  S33,  841 
Epiphyseolitis.  818 
Epiiihyseolysis,  176 
Epi])hysitis.  acute  infectious.  Sit 
Epiplocele.  713 
Epispadias,  633 
Epistaxis.  264.  564 
Epithelioma.  325 

columnar  cell,  328 

cylindric  cell,  328 

pearl.  326 

primary,  of  spleen,  430 

squamous,  325 

of  esophagus,  693 

of  mouth,  685 

of  salivary  glands,  68g 

of  serous  membranes,  359 

sites  of.  327 

tuV)ulated.  321) 
Ef)ithelium  in  sputum.  ((47 

in  urine,  935 
Epulis.  356,  686 
Erlicki's  solution,  3; 
Erosions  of  stomach.  701 
Erysipelas,  streptococcus  of,  115 
Elrythrasma,  164 
Erythrocidins,  1 15 
PIrythrocruorin,  411 
Erythrocyte,  407 
Erythrocytolysin,  78 
Erythrocytolysis.  78.  410 
Esmarch's  tube  plates,  907 
Esophagismus,  69  i 
Esophagitis,  550,  690 

phlegmonous,  691 
Esophagomalacia,  693 
Esophagus.  680 

acquired  dilatation  of,  692 

actinomycosis  of,  691 


Eso[)hagus.  anemia  of.  0(>o 
atonic  dilatation  of,  692 
atresia  of,  690 
carcinoma  of,  693 
congestion  of,  690 
diffuse  dilatation  of,  6ij2 
gummata  of,  69  1 
hyperemia  of,  6go 
hysteric  stricture  of.  69 1 
inorganic  stricture  of.  6<)i 
malformations  of,  6(>o 
normal  structure  of.  6S() 
organic  stricture  of,  601 
perforation  of,  693 
jKJStmortem  examination  of,  19 
]3ulsion  diverticula  of.  692 
sarcoina  of.  693 
simple  stricture  of,  692 
spasmodic  stricture  of.  6(ji 
spontaneous  rupture  of,  693 
squamous  epithelioma  of,  603 
streptothricosis  of,  691 
stricture  of.  691 
structure  of,  689 
syphilis  of,  691 
thrush  of.  691 
traction  diverticula  of.  6()2 
traction-pulsion     diverticulum     of. 

603 

tuberculosis  of.  69  i 

tumors  of.  693 
Etiology,  55,  66 

Evisceration,  Letulle's  method,  26 
Exostoses.  340.  808 
Exostosis,  chondroid,  ^^i 
Exstrophy  of  bladder,  633 
Exudates.  269 

Eve.    inoculations   into   anterior  cham- 
ber of,  925 


Face,  cleft,  67 

hemihypertrophy  of,  So  7 
Family,  hemophilic,  genealogic  tree  of, 

263 
Farcy.  161 
Farcy-V)ud.  161 
Farina  kettle.  (>oo 
F'asciola  hepatica.   192 
Fasciolid;e.  192 
Fastigium.  379 
Fat.  necrosis  of.  25s 

perirenal,  atrophy  ot.  034 
Fauces,  gangrene  of,  S57 
Favus.  1 63 
Febris  amatoria.  421 
Femur,  osteophytes  on.  808 
Ferments,  amylolytic.  86 

diastatic,  86 

lipolytic.  86 

peptonizing,  86 

proteolytic,  86 
Fever.  374 

blood -'changes  in.  380 

cerebrospinal,  848 


966 


INDEX. 


Fever,  changes  in  organs,  380 

enteric,  728 

intermittent,  379 

lung,  597 

malaria,  liver  in,  746 

malta,  117 

paratyphoid,  731 

remittent,  379 

splenic,  124 

surgical  aseptic,  376 

syphilitic,  178 

Texas,  79 

typhoid,  138,  728 

Widal's  test  for,  931 
Fibers,  elastic,  in  sputuin,  947 

of  muscles,  788 
Fibro-adenoma,  318 
Fibroblasts,  302 
Fibroid,  recurrent,  353 
Fibroma,  341 

angio-,  342 

corneal,  of  spleen,  436 

durum,  342 

lamellar,  of  spleen,  436 

lipoinatodes,  342 

molle,  342 

of  brain,  877 

of  heart,  503 

of  muscle,  797 

of  stomach,  712 

of  thyroid,  783 

ossificum,  342 

petrificum,  343 

simple,  341 

telangietaticum,  342 
Fibroneuromata,  320,  893  i 

Fibrosarcoma,  353 
Fibrosis,  arteriocapillary,  526 

dystrophic,  498 

local  splenic,  436 

of  muscle,  791 

pancreatic,  771 

substitutive,  297 
Filaria  Bancrofti,  209 

bronchialis,  212 

embryo  of,  207 

hominis  oris,  212 

loa,  212 

medinensis,  210 

sanguinis  hominis,  207 
diurna,  208 
in  urine,  937 
nocturna,  208 
perstans,  208 
Filariae,  table  of,  208 
Filariosis,  207 
Filum  terminale,  834 
Fissura  abdominalis,  62 

sterni,  62 

vesic;c,  633 
Fistula,  thyroglossal,  776 
Fistulae,  branchial,  674 
Fixation,  process  of,  33 

of  tissue  by  alcohol,  35 

by  bichlorid  of  mercury,  34 


Fixatives,  ^^ 
Fixator,  102 

Flagella,  Loffler's  method  of  staining, 
914 

Pitfield's  method  of  staining,  915 
Flea,  dog,  213 

human,  213 

sand,  213 
Flemming's  solution,  ;^^ 
Fluke,  blood,   194 
Flukes,  192 
Foam-liver,  739 
Foam-organs,  135 
Foot-and-mouth  disease,  675 
Forceps,  bone-cutting,  29 

cover-glass,  38 

dissecting,  20 

Stewart's  cover-glass,  912 
Formalin,  31 
Formation  of  gas,  84 
Fracture  of  bone,  819 
Fragilitas  ossium,  809 
Fragmentation  of  thrombus,  276 
Friedlander's    method    of    staining    for 

capsule  of  Bacillus  pneumoniae,  128 
Friedreich's  ataxia,  887 
Frog,  leukocytes  of,  289 
Fungi,  mould,  162 

nonpathogenic,  in  urine,  936 

pathogenic,  in  urine,  937 
Fungus  hematodes,  335,  362 

ray,  166 

thrush,   166 


Gabbet's  stain  for  tubercle  bacillus,  146 

Galactocele,  367 

Gall-bladder,  empyema  of,  764 

fibrinous  inflammation  of,  764 

inflammation  of,  550,  763 

phlegmonous  inflammation  of,  764 

pseudomembrane  of,  764 

purulent  accumulation  in,  764 

tuberculosis  of,  764 

tumors  of,  766 
Gall-stones,  765 
Gametes,  184 

Ganglia,     semilunar,     postmortem     ex- 
amination of,   17 
Ganglion  cells  of  nervous  system,  835 

pyramidal,  of  nervous  system, 
840 
Gangrene,  255 

circumscribed,  256 

diabetic,  258 

diffuse,  of  lung,  595 

dry,  258 

gaseous,  257 

hospital,  258 

infiaminatory,  255 

latent  pulmonary,  595 

line  of  demarcation,  257 

moist,  255 

multiple,  256 

of  lung,  595 


INDEX. 


()()■; 


Gangrt-nt--  i>f  luni,',  (.ircumscril)*.'!!,  5<)5 
cHlTusc.  5i)<) 

of  sjilecn,  438 

pancreatic.  770 

pulmonary.  545 

senile,  258 

spreading.  250 

symmetric.  250 

traumatic,  255 
Gas,  formation  of,  S4,  i>i6 
Gastralgia,  701) 
Gastrectasis,  70b 

acute,  707 

chronic,  708 
Gastritis.  550,  700 

acute  catarrhal,  700 

atrophic,  702 

chronic,  701 

croupous.  702 

degenerative,  700 

fibrinous,  702 

fibroid,  702 

hyperplastic  interstitial,  702 

phlegmonous,  702 

polyposa,  701 

pseudomembranous,  702 
Gastroliths,  608 
Gastromalacia,  b()5 
Gastroplegia,  707 
Gastroptosis,  697 
Gastrorrhagia,  698 
Gastroschisis.  63 

Gelatin,  liquefaction  by  bacteria,  84 
Gemmulic,  changes  in,  859 

of  nerves,  836 
Genitals,   internal,    postmortem   exami- 
nation of,  16 
Giant  growth,  216,  806 
Giants,  806 
Gigantol)lasts,  409 
Gilsons  method  of  celloidin  infiltration, 

Gingivitis,  phagedenic,  675 
Gland,  thyroid,  adenoma  of,  783 
anemia  of.  776 
atrophy  of,  777 
hyperemia  of,  776 
hypertrophy  of,  770 
Glanders,  i6o 

acute,  161 

chronic,  161 

"healed-in"  nodules  of,  162 

localized,  161 

of  bone,  819 

of  lung,  624 

of  mucous  membranes,  562 

of  nasal  mucosa,  566 

septicemic,  161 
Glands,  ductless,  775 
Gl^nard's  disease,  431,  767 
Glioma,  321,  875 

ependyma-cell,  321 

of  spinal  cord,  888 

site  of,  322 
Gliosarcoma,  321 


I   Gliosarcoma  of  brain,  876 
!  of  spinal  cord.  888 

Glossina  palpalis,  183 
Glossitis,  5^0,  678 

interstitial,  679 

parasitic,  679 

pseudomembranous,  679 
Glossophygia,  679 
Glottis,  edema  of,  573 
Glycemia,  407 

Glycerin-ether  mixture,  Unna,  49 
Glycogen,  239 
Gnats,  213 
Goiter,  780 

aberrant,  782 

acute,  782 

benign,  782 

chronic,  782 

cystic  colloid,  781 

ectopic,  782 

exophthalmic,  782 

fibroid,  781 

hemorrhagic,  781 

hyperplastic,  781 

intratracheal,  575,  782 

large  cystic,  781 

lingual,  685,  782 

malignant,  782 

mediastinal.  782 

neoplastic,  782 

nodular  fibroid,  781 

parenchymatous,  781 

submaxillary,  782 

telangiectatic,  782 

tracheal,  782 

vascular,  782 
Golgi's  method,  Berklev"s  modification 

of,  836 
Gonococcemia,  109 
Gonococcus,  107 

in  urine,  937 

local  infections  of,  108 

pathogenesis  of,  108 

svstemic  infection  by.   io(j 
Gonorrhea,  92,  108,  550,  559,  672 
Gonotoxin,  112 

Gowers'  hemoglobinometer,  390 
Gram's  iodin-iodo-potassic  solution,  914 

method  of  staming,  <)i4 
Granulation,  basophilic,  410 
Granules,    metachromatic,    of    Haeillus 

dii)htheri£e,  119 
Graves's  disease.  777,  782 
Gray   induration,   of  unresolved   pneu- 
monia, O12 
Greensickness,  421 

Grenachcr's  alcoholic  borax-carmin,  45 
Grooved  director,  15 
Group,  agglutinophore.  104 
Guinea-worm  disease,  a  10 
Gumma,  179 

cardiac,  502 

of  esophagus,  691 

of  liver,  in  congenital  syphilis,  758 

of  mouth,  678 


968 


INDEX. 


Gumma  of  muscle,  797 

of  pituitar)'  body,  877 


Habits,  68 

Ha3matochyluria,   210 

H:emosporidia,   186 

Haffkine's  protective  inoculation,  132 

Hair-balls  in  stomach,  698 

Halisteresis  of  bone,  810 

Hand,  battledore,  806 

Haptophore  group,  loi 

Harelip,  673 

Harris's  hematoxylin,  47 

Head,  postmortem  examination  of,  20 

Healing  by  second  intention,  305 

by  third  intention,  306 
Heart,  482 

abdominal,  483 

acquired  malposition  of,  485 

acute  dilatation  of,  517 

albuminoid  infiltration  of,  490 

amyloid  infiltration  of,  490 

aneurysm  of.  501 

brown  atrophy  of,  488 

calcareous  infiltration  of.  490 

cervical.  483 

chondroma  of,  503 

chronic  dilatation  of,  518 

cloudy  swelling  of.  491 

concentric  hypertrophy  of,  515 

diffuse  fatty  degeneration.  491 

dilatation  of,  with  thickening,  515 
with  thinning,  515 

diseases  of  blood-vessels  of,  501 

eccentric  hypertrophy  of.  5  1 5 

edema  of,  520 

extreme  fatty  infiltration,  226 

fatty  degeneration  of,  491 

fibroma  of,  503 

general  atrophy  of,  488 

general  fatty  degeneration  of,  491 

granular  degeneration  of,  491 

gumma  of,  502 

hyaline  degeneration  of,  493 

hydatid  cysts  of,  503 

hypertrophy  of,  515 

hypoplasia  of,  487 

inflammation  of,  494 

influence  of  insufficiency  on,  518 
of  stenosis  on,  514 

lardaceous  disease  of,  490 

lipomatosis  of,  490 

malformations  of,  485 

of  blood-vessels  of,  486 
of  valves  of,  487 
of  walls  of,  485 

malposition  of,  483 

metastatic  abscess  of,  495 

mobile,  485 

muscle,  toxic  degeneration  of,  493 

myxoma  of.  503 

normal  structure  of,  482 

orifices,  narrowing  of,  513 
obstruction  of,  513 


Heart  orifices,  stenosis  of,  513 

partial  or  local  fatt}^  degeneration 
of,  492 

pectoral,  484 

pigmentary  infiltration  of.  491 

postmortem  examination  of,  1 1 

pre-aortic  stenosis,  515 

removal  of,  postmortem,  12 

rhabdomyoma  of,  503 

rupture  of,  503 

sarcoma  of,  503 

showing  villous  pericarditis.  464 

simple  hypertrophy  of.  515 

size  of  normal.  483 

structure  of,  482 

subvalvular  constriction,  516 
stenosis,  515 

tabby  cat,  491 

tiger.  491 

toxic  degeneration  of,  493 

tubercvilosis  of,  502 

tumors  of,  503 

valves,  incompetency  of,  514 
insufficiency  of,  514 

wall,  syphilis  of,  502 

wandering.  485 
Heat  in  inflammation,  298 
Heidenhain's  solution.  34 
Hemangiomata,  345 

cavernous,  345 

plexiform,  346 

simple,  345 
Hemarthron,  264,  826 
Hemarthrosis.  263 

of  hemophilia,  826 
Hematemesis.  699 
Hematencephalon,  264 
Hematocele.  264,  369 
Hematocrit,  403 
Hematoidin,  233 
Hematoma.  264 

of  muscle,  791 

paranephric,  634 
Hematomyelia,  264,  880 
Hematoxylin,  46 
Hematuria,  264,  637 

endemic,  193 

malaria,  79 

parasitic,  193,  638 

renal,  637 
Hemihypertroph}-  of  face,  807 
Hemochromatosis,  234 
Hemocytolysis,  417 
Hemocytometer.  Thoma-Zeiss,  399 
Hemofuscin,  234 
Hemogelometer.  405 
Hemoglobin,  411 

estimation  of,  in  blood,  390 

percentage  of,  in  blood,  398 

reinarks    on    methods    of    estima- 
tion, 398 

scale,  Talqvist's.  397 
Hemoglobinemia,  233.  417 
Hemoglobinometer,  Dare's,  395 

Gowers',  390 


1  \  u  !•;  x . 


909 


Heini>L,'l()l>in«>nu'tc-r,  Oliver's,  31; i 

\on  Fk'ischr.s,  ^(jo 
Ht'niugl(jhinuria,  23,^,  41S 

epidemic,  202 

paroxysmal,  41S 
Hemolymph-nodes.  442 
Hemolysin,  7S 

bacteria  producing.  81 
Hemolysis,  7S,  233,  417 
Hemopericardium,  2O4,  471; 
Hemoperitoneum.  204,  471* 
Hemojihilia,  2fi2 

hemarthrosis  of.  S26 

renal,  63 S 
Hemoptysis,  264.  375.  5S4 

parasitic,  iq2 
Hemorrhage.  261 

arterial,  261 

capillary.  261 

cerebral.  264,  862 
etiology  of,  862 

effects  of,  264 

extradural.  862 

from  larynx,  568 

from  mucous  memVjrane.  542 

from  nose.  564 

intestinal.  711) 

into  joints.  S26 

into  muscle,  -jqi 

into  nerves.  889 

into  pancreas,  768 

into  spinal  cord.  880 

into  spleen.  436 

into  suprarenals,  785 

intracranial.  861 

intradural.  862 

mixed.  261 

occult  gastric.  609 

of  intestine.  264 

of  stomach.  6q8 

jtancreatic.  76S 

per  diabrosin.  263 

per  diapedesin,  261 

per  rhcxin.  261 

purjturic.  264 

svstemic  phenomena    induced    l>v 
'  265 

subdural,  862 

under  periosteum,  803 

venous.  261 
Hemorrhagin.  79 
Hemorrhoids,  736 

vesical,  668 
Hemosiderin,  233 
Hemothorax,  479 
Hepar  mobile,  739 
Hepatitis.  749 

acute  nonsuppurative.  740 
parenchymatous.  749 

chronic  interstitial.  753 

parenchymatous,  747 

suppurative.  749 
Hepatization,  white,  of  lung.  623 
Hepatolysin.  79 
Hepatosis.  730 


Ihridil.iry  ataxia,  s>7 
IliTcdity.  67 
Hermann's  solution,  _^_^ 
lIiTtnapiiniilismus  verus.  63 
Hermaphroditism,  63 
Hernia,  7  13 

body  of,  713 

congenital  diaphragmatic,  58 

diaphragmatic,  697 

external.  713  , 

incarcerated,  713 

internal.  7  13 

intestinal,  forms  of,  713 

irreducil)le,  7  13 

of  lung,  581 

reduciole,  713 

sac  of,  7  1 3 

strangulated,  713 
Herpes  exedcns,  330 

tonsurans.  164 
Hesse's  aeroscope,  911 
Hetcrojjlasia,  220 
Heterotaxy,  485 
Heterotopia   of  gray   matter   of   l)rain. 

847 

of  spinal  cord,  845 
His's  method  of  staining  capsules.  916 
Hodgkin's  disease.  430,  447 
Holorrhachischisis.  843 
Howslip's  lacunie,  800 
Hydatid  cysts,  see  Echinococcus.  198 
Hydremia.  406 
Hydrocephalus,  external.  270 

internal,  270 

acquired.  850 
congenital.  846 
Hydromicrocephaly,  84 7 
Hydromyelia.  844 
Hydromyelocele,  844 
Hydronephrosis.  663 
Hydropericardium.  270.  433.  320 
Ilydroperitoneum,  270,  433 
Hydrops  arthrosis,  434,  826 

articuli.  270 

cystidis  felle;e.  763 

ex  vacuo.  830 

universalis.  270 
Hydrothorax.  270,  433,  320 
Hygroma,  368 
Hymenolepsis  diminuta,  ig8 

nana.  107 
Hyperemia.  260 

active.  260 

of  brain,  837 

of  spinal  cord.  S70 

arterial.  260 

collateral.  260 

compensatory,  260 

of  bone.  803 

of  bronchi,  575 

of  dura  mater,  848 

of  esophagus.  690 

of  intestine,  7 19 

of  kidtiey,  636 

of  larynx,  569 


970 


INDEX. 


Hyperemia  of  liver,  740 

of  lung,  582 

of  mucous  membranes,  541 

of  pancreas.  7  68 

of  spinal  cord,  879 

of  stomach,  698 

of  thyroid,  776 

passive,  265 

of  brain,  858 

of  pia-arachnoid,  850 

venous,  265 
Hyperergia,  215 

Hyperesthesia  of  olfactory  nerves,  568 
Hyperinosis,  406 
Hyperkeratosis,  248 
Hypernephroma,  240,  663 
Hyperosmia,  568 
Hyperplasia,  219 

acute,  of  spleen,  434 

noninflammatory,  297 

progressive  lymphadenoid,  447 
Hyperthermia,  374 

Hypersecretion  of  salivary  glands,  687 
Hyperthyroidism,  7S3 
Hypertrophy,  215 

compensatory,  218 

concentric,  of  heart,  515 

congenital,  of  intestine,  715 

eccentric,  of  heart,  515 

life  history  of,  517 

limitations  of,  219 

numerical,  218 

of  arteries,  533 

of  bladder,  669 

of  bone,  806 

of  brain,  847 

of  heart,  489,  515 

of  kidney,  635 

of  liver,  742 

of  mammse,  216 

of  mucous  membranes,  542 

of  muscle,  790 

of  spleen,  433 

of  suprarenals,  785 

of  thyroid,  779 

physiologic,  218 

post-nasal  adenoid,  567 

simple,  218 

of  heart,  515 
Hyphae,  162 
Hyphomycetes,  162 
Hypinosis,  406 
Hypoleukocytosis,  412 
Hypoplasia,  222 

asymmetric,  223 

of  heart,  487 

of  spleen,  432 

partial,  of  brain,  847 
Hypospadias,  633 

perineoscrotalis,  634 


Ichthyosis,  248 

linguae,  317 
Icterus,  essential  hemorrhagic,  747 


919 


Icterus  gravis,  747 

Idios\mcrasy,  67 

Ileitis,  550 

Ileocolitis,  720 

Ileus,  acute  paralytic,  707 

adynamic,  707 
Immunisin,  102 
Immunity,  94 

absolute,  94 

accumulation  theory  of,  98 

acquired,  95 

active,  95 

antitoxic,  97 

artificial,  96 

bacteriolytic,  97 

cellulohumoral  theory  of,  99 

Ehrlich's  theory  of,  99 

exhaustion  theory  of,  98 

experimental,  96 

forms  of,  94 

induced,  96 

local,  97 

natural,  95 

passive,  96 

phagocytic  theory  of,  98 

side-chain  theory  of,  99 

theories  of,  97 
Implantation,  mural,  378 
Incubation  of  cultures,  922 

of  hanging-drop  cultures. 
Incubator,  922 
Indol,  production  of,  920 

tests  for,  920 
Induration,  brown,  519 

of  mucous  membranes,  544 

chronic  splenic,  435 

cyanotic,  519 

fibroid,  of  lung,  611 

gray,  of  lung,  588 
Infantilism,  symptomatic,  222 
Infants,  sublingual  growth  in,  679 
Infarct,  281 

anemic,  281 

hemorrhagic, 
of  lung, 

white,  281 
Infarction  of  liver, 

of  lung,  585 

renal,  637 

splenic,  437 
Infarcts,    multiple 
282 

uratic,  of  kidney,  635 
Infection,  Bilharzia  hematobia,   193 

extension  by  blood,  92 
by  continuity,  92 
by  lymphatics,  92 
inhalation,  by  tubercle  bacillus,  14^ 

mixed,  90,  377 

of  appendix,  propagative,  722 

of  lymph-nodes,  443 

of  mouth,  678 

by  bacteria,  678 
paths  of,  90 
pure,  90 


283 
283,  585 

742 


anemic,    of   kidnev 


IN'OKX. 


97' 


Infection,  scconciary,  .:?7  7 
sinj,'lc,  Qo,  .S7  7 
specific,  2oS 

systemic,  by  the  gonococcus,   loy 
tertiary,  377 
through  air-passages,  (jj 
through  ahinentary  canal,  g  1 
through  birth  canal,  t)2 
through  genito-urinary  system,  92 
throng li  mouth,  qi 
through  skin,  90 
tonsillar.  ()r 
transplacental,  90 
Infections,  05 

concurrent,  90,  377 
chronic,  of  bone,  817 

of  joints,  831 
local,  376 
Infiltration,  224 

albuminoid,  227 

of  heart,  490 

of  liver,  745 

of  mucous  membranes,  544 
amyloid,  227,  530 

artificial  production  of,  229 

causes  of,  228 

chemic  tests  for,  230 

morbid  anatomy  of,  230 

of  blood-vessels,  530 

of  heart,  490 

of  muscle,  791 

sites  of,  229 
and  degeneration,  224 
bacony,  227.     See  Amyloid. 
calcareous,  237 

into  joints,  825 

of  heart.  490 

of  mucous  membranes,  545 

of  pancreas,  769 

of  spleen,  434 

of  suprarenals,  7S5 
cholesterin,  240 
extreme  fatty,  of  heart,  226 
fatty,  225 

causes  of,  225 

of  heart,  489 

of  liver,  743 

of  inucous  membranes,  544 

of  muscle,  791 

of  pancreas,  768 

sites  of,  226 
fibrous,  of  myocardium,  495 
glycogen,  239' 
hemorrhagic,  264 

of  lung,  585 
hydropic,  240 
into  joints,  825 

lardaceous,  227.     See  Autyloul. 
methods  of,  35 
of  liver,  743 
of  muscle.  791 
of  tissue  with  ceiloKhn,  42 

with  parallin.  35 
paraffin,  method  of,  36 
pigmentary,  231 


Infiltration,  pigmentary  of  bronchi,  578 

of  heart,  491 

of  liver,   741; 

of  lymph-nodes,  443 

of  mucous  membranes,  542 

of  muscle,  791 

of  spleen,  433 
purulent,  29O 
waxy,  227 
Inflammation,  285 
acute,  297 
and  repair,  285 
aseptic,  298 
atrophic,    of    mucous   membranes, 

55° 
chronic,  297 

hyperplastic,    of   serous   mem- 
branes, 473 
productive,     of    serous    mem- 
branes, 473 
degenerative  of  kidney,  640 
diphtheritic,  of  mucous  membranes, 

557 
etiology  of,  285 
fibrinous,    of   mucous   membranes, 

5.50 
follicular,    of   mucous   membranes, 

550 
gangrenous,  of  mucous  membranes. 

557 

gonorrheal,  550 

heat  in.  298 

hemorrhagic,      of     mucous     mem- 
branes, 554 
of  serous  membranes,  472 

hypertrophic,     of     mucous     mem- 
branes. 549 

interstitial,  29S 

intravascular  changes,  288 

migrating  leukocytes  in,  289 

morbid  physiology  of,  20S 

of  arteries,  520 

of  colon,  722 

of  joints,  826 

of  kidney,  640 

of  larynx,  569 

of  liver,  749 

of  mouth,  675 

of  muscle,  791 

of  nasal  mucosa,  565 

of  nerves,  889 

of  periosteum,  803 

of  serous  membranes,  456 

of  spinal  cord,  8S0 

of  suprarenals.  780 

of  thyroid.  7S0 

of  veins,  534 

pain  in,  298 

parenchymatous.  208 

perivascular  changes,  290 

plastic,  of  pericardium.  461 

of  mucous  membranes,  550 

productive,  297 

pseudomembranous,      of      mucous 
membranes,  550 


972 


INDEX. 


Inflammation,  septic,  298 

serous,  of  mucous  membranes,  548 

subacute,  297 

systemic,  phenomena  of,  299 

terminations  of,  293 

vascular  changes,  287 
Influenza,  126 

Inhalation,  inoculation  by.  925 
Inoculation  by  feeding,  926 

by  inhalation,  925 

by  tissue  implantation,  925 

into  anterior  chamber  of  the  eye, 

925 

intracranial,  926 

intraperitoneal,  924 

intravenous,  925 

of  animals,  923 

protective,  for  cholera,   144 

subcutaneous,  of  animals,  924 
Inoma,  341 
Insecta,  213 

Insects  and  communicable  diseases,  214 
Instruments  for  postmortem,  i 
Insufficiency,  influence  of,  on  heart,  518 

of  heart  valves,  514 
Intestine,  acquired  dilatation.  715 

actinom^'cosis  of,  732 

acute  dilatation  of,  707 

acute  paralytic  distention  of,   707, 

715 
atresia  of,  714 
bacteria  of,  720 
calculi  of,  736 
carcinoma  of,  734 
chronic  caseous  tuberculosis  of,  732 
chronic    hyperplastic    tuberculosis 

of,  733 

congenital  hypertrophy  of.  715 

congestion  of,  719 

dilatation  of,  707,  715 

gangrene  of,  721 

hemorrhage  of,  264,  721 

hyperemia  of,  719 

inflammation  of,  720 

intussusception  of,  716 

invagination  of,  716 

malformations  of,  714 

malpositions  of,  712 

miliary  tuberculosis  of,  732 

normal,  712 

papillary  adenoma  of,  734 

papilloma  of,  734 

postmortem  examination  of,  19 

sarcoma  of,  735 

stenosis  of,  714 

structure  of,  712 

syphilis  of,  731 

tuberculosis  of,  732 

tumors  of,  734 

venal  distomatosis  of,  735 

volvulus  of ,  7  1 2 
Intoxication,  76 

microbic,  375 

septic,  375 
Intoxications,  372 


Intussusception,  ileocecal,  7  i  7 
ileocolic,  717 
of    intestine,  morbid    anatomy    of, 

717 
Intussusceptum.  717 
Intussuscipiens,  717 
Invagination,  7  i  7 

enteric,  717 

of  colon,  717 

of  intestine,  716 
Inversio  vesicae,  633 
Involucrum,  815 
lodin  reaction,  3S8 
lodophilia,  240,  388 
Ischemia,  259 

collateral,  260 

compensatory,  260 
Ischiopagus,  63 
Itch,  212 

ground,  206 
Ixodes  ricinus,  213 


Jaundice,  234 

hematogenous,  235 

hepatogenous,  235 

malignant,  747 
Jaw,  prognathous,  806 
Jejunitis,  720 
Joints,  798,  825 

ankylosis  of,  832 

arborescent  lipoma  of,  829 

calcareous   infiltration   into,    825 

Charcot's  disease,  830 

chronic  caseous  tuberculosis  of,  83 1 

chronic  infections  of,  83  i 

dropsy  of,  827 

fattv  degeneration  of,  823 

hemorrhage  into,  826 

hyaline  degeneration  of,  825 

infiltration  into,  825 

inflammation  of,  826 

loose  bodies  in,  826 

luxation  of,  825 

malformation  of,  825 

malposition  of,  825 

mucoid  degeneration  of,  825 

neurogenous  arthropathies  of,  830 

neuropathic  diseases  of,  830 

postmortem  examination  of,  26 

pseudo-ankylosis  of,  832 

spinal  arthropathies,  830 

syphilis  of,  832 

true  ankylosis  of,  832 

tuberculosis  of,  830 


Kahler's  disease,  824 

Kaiserling's  solution,  32 

Kakke,  890 

Kalteyer's  cover-glass  forceps,  913 

Kaolinosis,  232 

Karvokinesis,  300 

Karyolysis,  413 

Karvomitosis,  ^co 


INDKX. 


V7.? 


Kelis,  343 

Keloid,  343 

Keratin,  24S 

Keratitis,  asper^illus,  103 

Keratosis,  24S 

Kidney,  absence  of,  632 

adenosarcoma  of,  661 

angioniata  of,  661 

arteriosclerotic  contracted,    O53 

atrophv  of,  635 

cirrhotic,  652 

congestion  of,  637 

contracted.  652 

cyanotic,  (137 

cystic  degeneration  of,  665 
disease  of,  665 

cysts  of,  663 

degenerations  of,  636 

degenerative  inflammations  of,  640 

diseases  of,  634 

tibroid,  652 

floating,  633 

gouty,  652 

granular,  652 

hob-nail,  653 

horseshoe.  631 

hydatid  cysts  of,  665 

hyperemia  of,  636,  637 

hypertrophy  of,  635 

inhltrations  of,  635 

inflammation  of.  640 

in  lymphatic  leukemia,  427 

lardaceous  disease  of,  657 

large  white,  640 

leprosy  of.  661 

malformations  of,  620 

malpositions  of,  629 

massive  tuberculosis  of,  660 

medical  diseases  of,  635 

movable,  632 

multiple    anemic    infarcts    of,    282 

normal,  628 

papilloma  of,  662 

polycystic,  665 

postmortem  examination  of,    16 

sarcoma  of,  662 

sclerotic,  652 

single,  63  1 

small  white,  649 

solitary,  630 

surgical  diseases  of,  635 

syphilis  of,  661 

tuberculosis  of,  660 

tumors  of,  661 

uratic  infarcts  of,  407 
Killing  agents.  ^^ 
Knife,  graduated  brain,  18 

Valentines.  ^^ 
Koch's   alkaline-beef-peptone    bouillon. 
900 

law,  S3 

syringe.  925 
Koch-Erhlich  anilin  water  solution,  912 
Koch-Weeks's  bacillus,  133 
Kyphosis,  8 1  7 


Labels,  46 

Laceration,  subcapsular,  of  sjileen.    140 
Lacteals.  metastasis  of,  314 
Laennec's  cirrhosis  of  liver,  753 
Laryngitis.  569 
Larynx.  568 

actinomycosis  of,  572 

calcihcaiion    of   cartilages   of,    573 

cancers  of,  574 

chronic  edema  of,  573 

congestion  of,  569 

fibrous  polypi  of.  575 

functional  stenosis  of.  574 

hemorrhage  from,  568 

hyperemia  of,  569 

hypoplastic.  568 

inflammation  of,  569 

inflammatory  stenosis  of,  374 

leprosy  of,  572 

lymphangioma  of.  575 

malformations  of.   568 

nonnal  structure  of.  568 

organic  stenosis  of,  574 

papilloma  of,  574 

phlegmonous  edema  of.  573 

postmortem  examination  of,    15 

rhinoscleroma  of,  572 

sarcoma  of,  575 

serous  edema  of,  573 

syphilis  of,  57  i 

syj)hilitic  stricture  of.  571 

tuberculoma  of,  571 

tuberculosis  of,  570 

tumors  of,  574 

typhoid  ulcer  of,  570 
Law,  Koch's,  83 

Muller's,  in  relation  to  neoplasms, 

•    5 '3 

Virchow's,  in  relation  to  neoplasms. 

Leather-bottle  stomach,  702 
Leiomyoma,  344 
Leontiasis  ossea,  807 
Lepra  mutilans,  159 
Leprolin,  157 
Leprosy,  157 

anesthetic,  158 

gangrenous,  159 

mixed  forms,  159 

nodular,  159 

of  bone,  819 

of  kidney,  661 

of  larynx,  572 

of  liver,  761 

of  lung,  623 

of  mucous  membranes.  562 

of  muscle.  797 

of  nasal  mucosa.  566 

of  pleura,  478 

of  spleen,  441 

smooth,  1 58 

trophoneurotic,  158 

tubercular,  159 
Leptomeningitis,  850 
Leptothricosis.  170 


974 


INDEX. 


Leptus  autuinnalis,  212 
Lesion,  macroscopic,  64 

microscopic,  64 
Lesions,  associated,  in  chlorosis,  422 
Lethargy,  African,  183 
Letulle's  method  of  evisceration,   26 
Leukemia,  424,  439 

blood  condition  in,  425 

lymphatic,  426 

myelogenous,  425 

myeloid,  425 
Leukocidins,  115 
Leukocytes,  melaniferous,  413 

migrating,     in    inflammation,     289 

of  a  frog,  289 

polymorphonuclear,  290 

table  of,  414 
Leukocythemia,  424.     See  Leukemia. 
Leukocytopenia,  412 
Leukocytosis,  413 

agonal,  416 

inflammatory,  416 

physiologic,  416 

toxic,  417 
Leukodermia,  236 
Leukolysis,  413 
Leukomyelitis,  881 
Leukopenia,  412 
Leukoplakia,  679 
Leukotaxis,  417 

Lightning,  marks  produced  by,    74 
Limitations  of  hypertrophy,  219 
Lipemia,  406 
Lipochromes,  236 
J  ipofibroma,  338 
Lipoma,  337 

arborescent,  of  joint,  829 

circumscribed,  338 

degenerations  of,  339 

diffuse,  337,  338 
of  muscle,  791 

"gravity  wandering,"  338 

infiltrations  of,  339 

myxo-,  339 

of  brain,  877 

of  muscle,  797 

of  stomach,  712 

simple,  338 
Lipomatosis,  226 

of  heart,  490 
Liquefaction  of  gelatin  by  bacteria,  84 

of  thrombus,  275 
Liquor  puris,  294 

sanguinis,  302,  405 
Line  of  demarcation,  257 
Linitis,  plastic,  702 

suppurativa,  702 
Lithopedion,  238 
Lithosis,  232,  543 
Liver,  737 

abscess  of,  749 

actinomycosis  of,  761 

acute  fatty  degeneration  of,  747 

acute  infectious,  749 

acute  yellow  atrophy-  of,  743,  747 


Liver,  adipopexic  function  of,  739 
albuminoid  infiltration  of,  745 
amebic  abscess  of,  750 
amyloid,  745 

antitoxic  function  of,  738 
atrophic  cirrhosis  of,  753 
atrophy  of,  742 
biliary  cirrhosis  of,  757 
chronic  congestion  of,  740 
cirrhosis  of,  753 
cirrhosis  anthracotica  of,  756 
coagulation  necrosis  of,  748 
congenital  syphilis  of,  758 
contracted,  753 
cystic  adenoma,  7O2 
cysts  of,  762 
emphysematous,  739 
fatty  cirrhosis  of,  756 
fatty  infiltration  of,  743 
fibroid,  753 
floatmg,  739 
foam,  739 

focal  necrosis  ot,  749 
functions  of,  737 
gin  drinker's,  753  , 

glycogenic  function  of,  738 
granular,  753 

hemolytic  function  of,  738 
hepatic  artery  zone  of,  737 
hepatic  vein  zone  of,  737 
hob-nail,  753 
hj^peremia  of,  740 
hypertrophic  biliary  cirrhosis,  757 
hypertrophy  of,  742 
infarction  of,  742 
infiltrations  of,   743 
inflammation  of,  749 
in  lymphatic  leukemia,  427 
in  malarial  fever,  746 
interlobular  cirrhosis  of,  755 
intralobular  cirrhosis  of,  755 
Laennec's  cirrhosis  of,  753 
lardaceous  disease  of,  745 
leprosy  of,  761 
malarial,  746 
malformations  of,  739 
malposition  of,  739 
metastatic  abscess  of,  749 
miliary    gummata,     of     congenital 

syphilis,  75S 
monolobular  cirrhosis,  755 
normal  structure  and  function  of, 

737 
nutmeg,  740 

obstructive  cirrhosis  of,  756 
parenchymatous    degeneration    of, 

747 
perilobular  cirrhosis  of,  755,  758 
pigmentary  infiltration  of,  745 
polylobular  cirrhosis  of,  755 
polylobulated,  of  congenital   syph- 
ilis, 758 
portal  vein  zone  of,  737 
postmortem  examination  of,  18 
pressure  atrophy  of.  743 


INI)  !•;  X  . 


';75 


Liver,  pseudocirrhusis  <>i.  75.S 

pyemic  abscesses  of,  750 

red  atrophy  of,  510,  740.  74.^ 

secretory  function  of.  738 

simple  atrophy  of,  742 

slate  colored,  740 

structure  of,  737 

syphilis  of,  758 

syphilitic  cirrhosis  of,  7')o 

traumatic  abscess  of,  750 

tr()])ic  abscess  of.  751 

tuberculosis  of,  -$g 

tumors  of.  761 

urea  production  by,  73S 

venous  cirrhosis  of.  753 
Lividity,  cadaveric,  5 
Livores  mortis,  5 
Locomotor  ataxia,  886 
Loffler's  alkaline  methylene-blue  solu- 
tion. 48,  Q13 

blood-serum  mixture,  Sq8 

method  of  tiagella  staming.  qi4 

methylene-blue  solution,  48.  1)13 
Ludwig's  angina,  559,  679 
Lung,  abscess  of,  592 

actinomycosis  of,  624 

acute  fulminating  edema  of.  583 

acute  disseminated  tuberculosis  of, 

151 
acute  miliary  tuberculosis  of.  618 
carcinoma  of,  626 
carnitication  of,  588 
caseous  tuberculosis  of.  620 
chronic  edema  of.  584 
circumscribed  gangrene  of.  595 
cirrhosis  of.  611 

collapse,  588 
collapse  of,  587 
congestion  of,  582 
diffuse  gangrene  of,  595 
disseminated  gangrene  of,  595 
embolism  of,  585 
emphysema  of,  588 
tiV^roid,  61 1 

fibroid  induration  of,  611 
gangrene  of,  595 
glanders  of,  624 
gray  induration  of.  588 
hemorrhagic  infarcts  of,  283,  585 
hemorrhagic  infiltration  of,  585 
hepatization  of,  600,  623 
hernias  of,  581 
hydatids  in,  627 
hyperemia  of,  582 
hypostatic  congestion  of,  582 
infarction  of,  585 
inHammations  of,  see   Pneumonia, 

507 

latent  gangrene  of,  595 

leprosy  of,  623 

localized  edema  of.  584 

malffjrmation  of.  581 

malposition  of.  581 

morbid  anatomy  of  chronic  ulcerat- 
ing tuberculosis  of,  620 


Lung,  normal  structure  of,  581 

parasites  in,  027 

postmortem  examination  of,  14 

sclerosis  of,  61  2 

senile  atrophy  of,  591 

simple  acute  edema,  583 

splenization  of,  588 

syphilis  of,  623 

true  cirrhosis  of,  613 

tuberculosis  of,  614 

tumors  of.  624 

ulcerative  tuberculosis  of,  620 

white  hepatization  of,  623 
Lupus,  156 

exedens,  156,  330 

non  exedens,  156 
Lutein,  236 
Luxation  of  joints,  825 

pathologic,  828 
Lymphadenia,  424.  447 
Lymphadenitis,  444 

quiescent  tuVjerculous.  446 

regional  tuberculous,  445 

scrofulous,  445 

syphilitic,  447 

tuberculous,  445 
Lymphadcnoma,  447 
Lymphangiectases  of  tongue.  686 
Lymphangiectasis,  538 
Lymphangioma,  346,  538 

cavernous,  347 

cysticum,  347 

of  larynx,  575 

of  tongue,  686 
Lymphangitis,  538 

acute,  538 

acute  reticular,  538 

acute  suppurative,  538 

acute  tubular,  538 

chronic,  538 

peribronchial  suppurative,  578,  594 
Lymphatics,  extension  of  infection  by,  92 
Lymphatism,  451 
Lymphemia,  426 
Lymph-nodes,  442 

adenitis  chronica  of.  444 

carcinoma  of.  440 

caseous,  of  tuberculosis.   154 

colloid  change  in,  443 

hyaline   degeneration   of,    443 

in  buVjonic  plague,  130 

in  lymphatic  leukemia,  427 

infections  of.  443 

lanlaceous  disease  of,  443 

mesenteric,    |>ostmortem  examina- 
tion of,   20 

jjigmentary  infiltration  of.  44; 

siircoma  of,  440 

tumors  of,  449 
Lymphocythcmia,  426 
Lymphoma.  347 

malignant.  447 
Lymphorrhagia.  2O5 
Lymphorrhca,  265 
Lymphosarcoma.  447 


976 


INDEX. 


Lymph-scrotum,  210,  537 
Lvmph-stream,  infection  by,  92 
Lymph-vessels,  536 

intlanimation  of,  538 

malformations  of,  536 

obstruction  of,  536 

tuberculosis  of,  539 

tumors  of,  538 
Lysis,  379 


Macroblasts,  409 

Macrocheilia,  347,  674 
Macrocytes,  408 
Macrocythemia,  408 
Macrocytosis,  408 
Macrogamete,  184 
Macrogametocyte,  184 
Macroglossia,  347,  674 

neurofibromatosa,  674 
Macrostoma,  674 
Maculae  albidte,  455 
Maggots,  214 
Malacosteon,  810 
Malaria,  liver  in,  746 

parasites  of,  190 
Mai  de  Caderas,  183 
Malformation,  58,  60 

embryologic  theory  of,  61 

nosologic  or  pathologic  theory  of, 
61 

of  bone,  801 

of  heart,  485 

of  joints,  825 

of  lung,  581 

of  muscle,  788 

of  pancreas,  767 

of  spleen,  432 

of  stomach,  695 

of  thyroid,  775 

of  valves  of  heart,  487 

of  walls  of  heart,  485 
Malformations,   classification  of,   62 

of  bladder,  633 

of  brain,  845 

of  bronchi,  575 

of  esophagus,  690 

of  intestine,  714 

of  kidney,  629 

of  larynx,  568 

of  liver,  739 

of  lymph- vessels,  536 

of  mouth,  673 

of  nose,  564 

of  spinal  cord,  841 

of  ureter,  633 

of  urethra,  633 
Malignancy,  latent,  349 
Mallein,  161 

Mallet  for  postmortem  case,  20 
Malposition,  58 

acquired,  59 

of  heart,  485 
of  lungs,  587 

congenital,  58 


Malposition  of  heart,  483 

of  intestine,  712 

of  joints,  825 

of  kidney,  629 

of  liver,  739 

of  lungs,  587 

of  pancreas,  767   . 

of  serous  membranes,  455 

of  stomach,  697 

of  thyroid,  775 

trauma  as  cause  of,  6c 
Malta  fever,  1 1 7 
Mammse,   hypertrophy  of,    216 
Marchi's  fluid,  244 
Mark,  strawberry,  345 
Marks  produced  by  lightning,    74 
Marrow,  adenoid,  427 

lymphoid,  427 

normal,  799  ,    * 

pyoid,  427 
Mast  cells,   stain  for,   in  blood,   388 
Mastigophora,  flagellated,  1S2 
Mayer's  acid  hematoxylin,  47 

albumen,  40 

carmalum,  46 
McCrorie's     method     of     staining     for 

flagella,  915 
Measures  of  capacity,  2 
Meat  poisoning,  123 
Meckel's  diverticulum,  714     ■ 
Mediastinopericarditis,  474 
Medium,  reaction  of,  919 

Wertheim's,  898 
Medulla  oblongata,  834 
Megacolon,  715 
Megaloblasts,  409 
Megalocytes,  408 
Megalogastria,  696 
Megastria,  696 
Melanin,  233 
Melanoblasts,  357 
Melanosarcoma,  356 
Melanosis,  234 

of  carcinoma,  324 

of  sarcoma,  356 
Membrana    propria    of    mucous    mem- 
brane, 540 
Membrane,  prophylactic,  471 

pyogenic,  470 
Membranes  of  nervous  system,  833 
Meninges,  833 

anemia  of,  850 

postmortem  exainination  of,   22 

syphilis  of,  85 4 
Meningismus.  853 
Meningitis,  456,  850 

acute,  851 

cerebrospinal,  851,  855 

chronic,  851 

chronic  alcoholic,  854 

en  plaque,  85 3 

fibrinous,  S51 

incidental,  851 

in  croupous  pneumonia,  606 

internal,  852 


INDKX. 


97  7 


Meningitis,  morbid  anatomy  of.  85 1 

posterior  basic,  851 

productive,  85  i 

suppurative.  470,  851 

traumatic,  85  i 

tuberculous,  853 
Meningocele,  844,  846 
Meningococcus.  1 1 1 
Meningo-encephalitis,  4 78 
Meningotoxin,  i  1  2 
Merorrachischisis,  843 
Merozoites,  184 
Mcrycism,  70() 
Mcsarteritis.  520 
Mesentery,  thrombosis  of,  711; 

cysts  of.  480 
Mesonephron.  633 
Metamorphoses.  241 
Metamorphosis,  colloid.  246 
-  fatty,  242 

of  mucous  membranes,  545 

hyaline,  247 

hydropic.  245 

keratoid,  248 

myxomatous,  246 

parenchymatous,  241 
Metaplasia,  2iq 

lymphoid,  442 
Metastasis   by   lymph-stream,    314 

by  the  lacteals.  314 

of  thyroid,  784 

of  tumors,  314 
Methyl  violet.  48 

Methylene-blue,  Loffler's  alkaline,  48 
Metrorrhagia,  264 
Microblasts.  4og 
Microcephaly,  847 
Micrococci,  106 
Micrococcus  cereus  albus,  113 

cereus  flavus,  113 

melitensis,  1 16 

agglutination  of.  1 1  7 

pyogenes  albus,  1 1 3 

pyogenes  aureus,  1 1 3 

pyogenes  citreus,  1 1 3 

tetragenous,  1 1 7 
Microcytes,  407 
Microcythemia,  407 
Microcytosis,  407 
Microgamete.  184 
Microgametocyte,  184 
Microgastria,  695 

primitive.  6q$ 

secondary,  695 
Microgyria,  847 
Micromyelia.  844 
Micron,  81 
Micro-organism,  facultative   '•'■' ■'  ''     >^: 

obligate  aerobic,  85 
Microscope,  laboratorv.  >o 

use  of,  5  I 
Microsomia.  802 
Microsporon  Audouini.  i'>4 

furfur,  164,  165 

minutissimum.  164 
63 


Microstoma,  674 
Microtome,  3<j 

Minot.  4  I 

Kaiivicr's.  40 

Kyder,  40 
Migration  of  leukocytes,  288 
Mikulicz  cell,  159 
Milk  as  a  culture-medium.  898 

coagulation  of.  by  bacteria,  84 

for  determining  production  of  acid 
by  l)acteria,  899 
Milk -leg.  I  16 
Milzbrand.  124 
Miracidium,  192 
Mite,  harvest.  21  2 
Mitosis,  300 
Mollities  ossium,  810 
Molluscum  tibrosum,  342 
Munarthritis,  826 
Monilia  conidia,  166 
Monococci.  106 
Mononucleosis,  292 
Monsters,  62 
Monstra  per  defectum,  62 

per  duplica,  63 

per  excessum.  62 

per  fabricam  alienam,  62 
Morbid  anatomy,  56 

histology,  56 
Morljus  anglicus.  822 

cixTuleus,  4S8 

maculosus  neonatorum,  262 

virgineus,  421 
Mordant.  91 5 
Mortitication,  255 
Mosquitoes,  213 

Anopheles,  214 

Stegomyia,  214 
Moss  cells  of  nervous  system,  835 
Mothers  mark,  345 
Mother-skein,  300 
Motility  of  bacteria.  82 
Motor    tract,    pvramidal,    agenesis    of. 

866 
Mounting  of  sections.  45 
Mounts,  stained,  microscopic  examina- 
tion of.  916 

unstained,    microscopic     examina- 
tion of.  916 

temporary,  of  bacteria,  913 
Mouth,  673 

adult  connective-tissue  tumors  of. 
686 

diffuse  suppuration  of  floor  of.  679 

gumma  of.  678 

infection  of,  by  bacteria.  678 

infection  through,  91 

inflammation  of,  675 

malformations  of.  673 

papillomata  of.  685 

putrid  sore.  673 

sarcomata  of.  68<) 

squamous   epithelioma   oi.    685 

syphilis  of,  67S 

tumors  of,  68  ^ 


978 


INDEX. 


Mucin,  337 

Mucosa,  bronchial,  pigmentary  infiltra- 
tion of,  578 
gastric,  infiltrations  of,  700 
Mucosae,  diseases  of,  540.     See  also  Mu- 
cous Membranes. 
medicomental  pigmentation  of,  544 
Mucous  membranes,   actinomjxosis   of, 
562 
acute  catarrh  of,  546,  547 
albuminoid  infiltration  of,  544 
amyloid  infiltration  of,  544 
atrophic  inflammation  of.   550 
atrophy  of,  542 
brown  induration,  544 
calcareous  infiltration   of,    545 
chronic     catarrhal    inflamma- 
tion of,  548 
chronic   hyperplastic   tubercu- 
losis of,  561 
chronic    infectious    inflamma- 
tions of,  560 
coagulation  necrosis  of,  545 
congestion  of,  541 
croupous  inflammation  of,  550 
diphtheritic   inflammation   of, 

.557 
diseases  of,  540 
dry  catarrh  of,  550 
fatty  degeneration  of,  545 
fatty  inflltration  of,  544 
fatty  metamorphosis  of,  545 
fibrinous  inflammation  of,  550 
follicular  inflammation  of,  550 
gangrenous    inflammation    of, 

557 
-     glanders  of,  562 

gonorrheal     inflammation    of, 

550 
granular  degeneration  of,   545 
hemorrhage  from,  542 
hemorrhagic  inflammation  of, 

554 
hyperemia  of,  541 
hypertrophic  inflammation  of, 

549 

hypertrophy  of,  542 

infiltrations  of,  542 

inflammations  of,  attended  by 
distinct  necrosis,  556 

leprosy  of,  562 

normal   structure   of,    540 

pigment  deposit  from  blood, 
544 

pigmentary  infiltration  of,  542 

plastic  inflammation  of,  550 

pseudomembranous  inflamma- 
tion of,  550 

rhinoscleroma  of,  563 

serous  inflammation  of,  548 

submucosa  of,  541 

suppurative  and  pustular  in- 
flammations of,  559 

suppurative  catarrh  of,  559 

syphilis  of,  562 


Mucous  membranes,  tuberculosis  of,  560 
tumors  of,  563 

patch,  179 
Muguet,  165,  166 
Miiller's  fluid,  31 

law,  in  relation  to  neoplasms,  313 
Multilocular  stomach,  696 
Mumps,  686 
Muscle,  abscess  of,  793 

actinomycosis  of,  797 

amyloid  infiltration  of,  791 

angioma  of,  797 

atrophy  of,  788 

chondroma  of,  797 

chronic  infection  of,  796 

cloudy  swelling  of,  791 

cold  abscess  of,  796 

degeneration  of,  791 

diffuse  lipoma  of,  791 

endomysium  of,  788 

epimysium  of,  788 

fatty  degeneration  of,  791 

fatty  infiltration  of,  791 

fiber,  granular  degeneration  of,  791 

fibers  of,  788 

fibroma  of,  797 

fibrosis  of,  791 

gumma  of,  797 

hematoma  of,  791 

hemorrhage  into,  791 

hyaline  degeneration  of,   791 

hydropic  degeneration  of,  791 

hypertrophy  of,  790 

infiltration  of,  791 

inflammation  of,  791 

intercostal,  inflammation  of,  794 

leprosy  of,  797 

lipoma  of,  797 

malformation  of,  788 

myxoma  of,  797 

osteomata,  797 

parasites  of,  797 

perimj-sium  of,  788 

pigmentary  infiltration  of,  791 

sarcolemma  of,  788 

secondary  cancer  of,  797 

secondary  sarcoma  of,  797 

syphilis  of,  796 

tuberculoma  of,  796 

tuberculosis  of,  796 

tumors  of,  797 

vacuolization  of  fibers,  791 

voluntary,  788 
Mycelium,  162 
Mycetoma,  169 
Mycoderma  aceti,  86 
Mycoses  of  blood,  377 
Mycosis,  275 

intestinalis,  123,  125 

tonsillaris  benigna,  170 
Myelemia,  425 
Myelin,  839 
Myelitis,  880 

acute,  880 

areas  of  softening  in  cord,  881 


INDKX. 


979 


Myelitis,  central,  S8  I  ' 

chronic,  880 
(JitTuse,  881 
disseminated,  881 
focal,  88 1 

morbid  anatomy  of,  88 1 
polio-,  788,  88 1 
secondary     to     intlammations     of 

pia-arachnoid,  881 
subacute,  880 
transverse,  88 1 
Myelocystocele,  844 
Myelocvstomeningocele,  S44 
Myelocythemia,  425 
Myeloma,  824 
Myelomatosis.  824 
Myelomeningocele,  843 
Myelotome,  24 
Myiasis,  214 

Myocardial  fragmentation,  493 
Myocarditis,  494 

acute  nonsuppurative,  494 
acute  parenchymatous,  494 
acute  suppurative.  495 
chronic  mterstitial,  495 
circumscribed  elastic,  499 
circumscribed  fibrous,  498 
diffuse  elastic,  500 
diffuse  interstitial,  498 
local  elastic,  499 
local  fibrous,  498 
parenchymatous,  494 
productive,  495 
sclerotic,  495 
segmentary,  493 
simple,  494 
Myocardium,  degeneration  of,  491 
fibrous  degeneration  of,  495 
fibrous  infiltration  of,  495 
fibrous  transformation  of,  4<)5 
foreign  bodies  in,  504 
infiltrations  of,  489 
inflammations  of.  494 
postmortem  changes  in,   403 
syphilis  of,  502 
wounds  of,  504 
Myoma,  343 

laevicellulare,  344 
of  stomach.  71  2 
strioccllulare,  344 
uterine,  344 
Myomalacia  cordis,  501 
Myopathy,  primary,  788 
Myosarcoma,  345 
Myosclerosis,  789 
dure.  498 
elastic,  498 
moUe,  498 
Myositis,  791 
acute,  791 

acute  diffuse  suppurative  intersti- 
tial, 792 
acute  nonsuppurative,  792 
acute    nonsuppurative    interstitial, 

797 


Myositis,  acute  suppurative,  792 

chronic  interstitial,  794 

chronic  ossifying,  794 

circumscribed  suppurative,  793 

tibrous.  794 

hemorrhagic,  792 

infectiosa,  792 

localized,  793 

ossificans.  794 

ossifying,  795 

parasitic.  7g4 

sclerosing,  7()4 

simple,  7<j2 

suppurative,  792 

tuberculous  interstitial  fibroid,  796 

with  contraction,  794 
Myotonia,  congenital,  791 
Myxedema,  247,  778 

congenital,  777 

post -operative,  779 
Myxofibroma,  342 
Myxolipomata.  339 
Myxoma.  347 

laryngeal.  575 
of  heart,  503 
Mvxoneuromata,  893 
Myxoneurosis     intestinalis     membran- 

acea,  725 
Myxosarcoma,  361 


Nagana,  183 
Nanism,  223 
Xanosoma,  223 
Nanosomia,  802 
Naples  paraffin  bath,  38 
Nasal  mucosa,  erectile  tumors  of 
glanders  of,  566 
inflammation  of,  565 
leprosy  of,  566 
papillomata  of,  566 
rhinoscleroma  of,  566 
syphilis  of,  566 
tuberculosis  of,  566 
tumors  of,  366 
Neck,  congenital  wry,  791 
cysts  of,  674 
emphysema  of,  568 
phlegmon  of.  680 
woodv  phlegmon  of,  680 
Necrobiosis,  241 
Necrosis,  249.  255 
cheesy,  254 
coagulation,  250 
of  liver,  748 

of  mucous  membranes,  545 
colliquative,  251 
direct,  249 
fat,  254 

focal,  of  liver,  749 
indirect.  249 
liquefaction,  250 
marasmic.  250 
neuropathic,  249 
of  bone.  812 


567 


980 


INDEX. 


Necrosis,  results  of,  250,  251 

senile,   230 
Needles  for  handling  sections,  43 

platinum  inoculating,  908 
Neisser's  method  of  staining  spores,  914 

stain  for  Bacillus  diphtlieriic,   119 
Nematodes,  202 
Neoplasms,  308 
benign,  315 
causes  of,  310 
classification  of,  315 
connective-tissue,  337 
epithelial,  316 
growth  of  interstitial,  313 
malignant,  315 
parasitic  influence  in,  311 
retroperitoneal,  480,  735 
Virchow's   law   in   relation   to,    313 
Nephrectasis,  665 
Nephritis,  640 

acute  catarrhal,  647 

desquamating,  647 
dift'use,  643,  647 
nonsuppurative        interstitial, 

647 
parenchymatous,  646 
suppurative,  641 
suppurative  interstitial,  641 
chronic  catarrhal,  648 
desquamative,  648 
diffuse,  648 
epithelial,  648 
parenchymatous,  648 
tubular,  648 
diffuse,  641 
exudative,  640 
glomerular,  647 
•in  croupous  pneuinonia,  606 
interstitial,  641 
parenchymatous,  641 
post-diphtherial,  644 
post-scarlatinal,  644 
productive,  640 
variolous,  644 
Nephrolithiasis,  658,  659 
Nephrolysins,  79,  645 
Nephroptosis  (ren  mobilis),  632 
Nerve-cells,  arkyochromes,  837 
arkystichochromes,  837 
degeneration  of,    method   of   dem- 
onstrating, 853 
demonstration  of,  837 
gyrochromes,  837 
karyochromes,  837 
processes  of,  835 
of  first  type,  836 
of  second  type,  836 
somatochromes,  837 
stichochromes,  837 
tigroid  substance  of,  837 
Nerve-fibers,     secondary     degeneration 

of,  860 
Nerves.  833,  835,  841 

axis-cylinder  of,  835 

bodies  of  Nissl  in  cells  of,  837 


Nerves,  circulatory  disturbances  in,  889 
degeneration  of,  889 
dendrites  in  cells  of,  836 
ganglion  cells  of,  835 
gemmulse  of,  836 
hemorrhage  into,  889 
in  alcoholic  multiple  neuritis,   891 
infiltration  of,  889 
inflammation  of,  889 
nodes  of  Ranvier  in,  841 
olfactory,  hyperesthesia  of,  568 
perineurium  of,  841 
primitive  sheath  of,  841 
regeneration  of,  893 
thermogenic,  373 
thermolytic.  373 
thermo-inhibitory,  373 
tuinors  of,  893 
Nervous  system,  833 

anatomy  of,  833 
cells  of  Purkinje,  841 
basket  cells  of,  841 
central,  833 

canal  of  the  cord,  842 
tuberculosis  of,  8 73 
disseminated  sclerosis  of,  874 
ganglion  cells  of,  835 
glia  cells  of,  840 
gray  matter  of,  840 
histology  of,  835 
large  ganglion  cells  of,  840 
inoss  cells  of,  835 
peripheral,  833 
sclerosis  of,  835 
small  pyramidal  ganglion  cells 

of,  840 
spider  cells  of,  835 
substantia  gelatinosa  centralis, 

841 
sympathetic,  833 
syphilis  of,  871 
white  substance  of,  8 40 
Neuritis,  889 
acute,  889 

interstitial,  890 
alcoholic  multiple,  89 1 
ascending,  889 
chronic,  889 
descending,  889 
interstitial,  891 
leprous,  890 

of  chronic  lead  intoxication,  891 
parenchymatous,  891 
Neurofibrils,  838 

changes  in,  859 
Neurofibroma,  320 
Neurofibromatosis,  342,  893 
Neuroglia,  834,  835,  840 
Neuroglioma,  ganglionic,  875 
Neurolipoma,  320 
Neuroma,  320 

amputation,  894 
amyelinic,  320 
cirsoid,  320 
false,  320 


I  N  D  K  X  . 


yHi 


\ 


euronui.  j^'anglionic.  320 

inyt'linic.  .^20 

plfxiforni,  320 

racemose,  ^20 

varieties  oi,  320 
euromyxoma,  320 
euron,  835 
curonophagia,  860 
evus  rtammeus,  345 

promincns,  346 

simpile.  345 

vasculosus,  346 

venosus.  345 
igrities  linguje.  (yji) 
issl.  bodies  of,  837 
oli  me  tangere,  330 
oma,  256,  558.  676 
ormal,  the.  58 
ormoblasts.  400 
ose,  564 

carcinoma  of,  566 

chronic     catarrhal     inflammation, 

565 

hemorrhage  from,  564 

malformations  of,  564 
osology,  56,  64 
ovy's  apparatus  for  anaerobic  cultures, 

017 


5  73 
166 
412 


Obesity,  226 

Obstruction,  esophageal,  692 

intestinal,  718 

of  bile-ducts,  765 

of  lymph-vessels,  536 

pyloric,  706 
Occlusion  of  vessels  of  brain.  864 
Occupation,  68 
Ochronosis.  234 
CEdema  laryngis, 
Oidium  albicans, 
Oligochromemia, 
Oligocythemia,  410 
Oliver's  hemoglobinometer,  301 
Oocyst,  184 
Ookinet.  184 
Opisthorcis  felineus,  102 

noverca,  193 

sinensis,  1Q3 
Opsonins,  qq 

Orbit,  postmortem  examination  of,  23 
Organisms  of  suppuration.  204 
Organization  of  thrtjmbus,  276 
Organizing  pneumonia,  604 
Orifices,  cardiac,  diameters  of,  483 
Orth's  fluid,  31 
Osseous  resorption,  800 
Ossification  of  blood-vessels,  330 
Osteitis.  810 

chronic  productive,  815 

condensing,  815 

deformans,  815 

rarefying,  815 
Osteoarthritis,  829 


Osteoarthropathy,     pulmonary     hy]>cr- 

trophic,  807 
Osteoblasts,  800.  801.  814,  821 
Osteochf)ndritis,  syphilitic.  175,  818 
Osteoma,  340 

cancellous.  340 

comj)act.  340 

eburnated.  340 

spongy.  340 
Osteomalacia.  810 
Osteomata  of  brain.  877 

of  muscle.  797 

of  thyroid.  783 
Osteomyelitis,  810 

acute  tuberculous.  817 

bacteria  in.  811 

circumscriV)ed.  8 1  2 
Osteophytes,  808 
Osteoporosis,  8og 
Osteosarcoma,  341,  361 
Osteosclerosis,  815 
Ostitis,  810 

Otitis  media  due  to  pneumococcus,  606 
Oxyuris  vermicularis,  203 
Ozena,  550.  566 


Pacchionian  bodies,  834 
Pachyacria,  806 
Pachyderma  laryngis,  569 
Pachydennatocele,  342 
Pachymeningitis,  848 

chronic  internal,  849 

hemorrhagic,  848,  849 

suppurative,  848 
Palate,  cleft,  674 
Panarthritis,  S2O 
Pancreas,  767 

annular,  767 

atrophy  of,  769 

calcareous  infiltration  of,    769 

calculi  of,  773 

cloudy  swelling  of,  769 

congenital  cystic  disease  of.  774 

congestion  of,  768 

cystadenoma  of.  774 

cystoma  of,  774 

cysts  of,  773 

di visum.  767 

fatty  infiltration  of,  768 

fibrosis  of,  771 

gangrene  of,  77^0 

hemorrhage  int'o,  768 

hvaline  transformati<ni  of,  769 

hyi)ercmia  of,  768 

inflammation  of,  769 

malformations  of,  767 

malposition  of,  767 

postmortem  changes  in.  767 

postmortem  exammation  of,  19 


sclerosis  of,  771 
structure  of,  767 
syjihilis  of,  773 
tuoerculosis  oi,  773 
tumors  of,  773 


INDEX. 


Pancreas,  Wirsung's  duct  of,  767 
Pancreatitis,  769 

acute  hemorrhagic,  769 
suppurative,  770 

chronic,  771 

interacinar,  772 
interlobular,  772 
interstitial,  772 

gangrenous,  770 

indurative,  771 
Papilloma,  316 

clinical  characters  of,  316 

fimbriatum  of  bladder,  671 

intracanalicular,  318 

of  bile-ducts,   766 

of  bladder,  671 

of  intestine,  734 

of  kidney,  662 

of  larynx,  574 

of  mouth,  685 

of  nasal  mucous  membrane,  566 

of  stomach,  709 

site  of,  316 

varieties  of,  317 

villous,  316 

of  gall-bladder,  766 
Pappenheim's  stain  for  tubercle  bacil- 
lus, 146 
Paraffin,     infiltration    of    tissue     with, 

35 
Paragonimus  westermanii,  192 
Paralysis,  acute  ascending,  882 

acute  bulbar,  86g 

glossolabiolarvngeal,  885 

infantile,  7 88,"  884 

Landry's,  882 

muscular,  pseudohypertrophic,  226, 
789 

progressive  bulbar,  885 
Paranephrosis,  634 
Paraosteal  abscess,  812 

suppuration,  804 

tuberculosis,  817 
Paraplegia,  ataxic,  888 

primary  spastic,  887 
Parasites,  animal,  181 

in  bronchi,  627 

in  lung,  627 

of  malaria,  186 

of  muscle,  797 

protozoal,  191 
Parasitic  hematuria,  638 
Parasynovitis,  826 
Parathyroids,  775 
Paratyphoid  bacillus,  731 

fever,  731 
Parosmia,  568 
Parotid  bubo,  686 

gland,  postmortem  examination  of, 
26 

hypersecretion  of,  687 

sclerosis  of,  686 
Parotitis,  686 

chronic  interstitial,  686 

indurative,  686 


Parotitis,  suppurative,  in  croupous  pneu- 
monia, 606 
Paroxysm,  malarial,  191 
Passages,  biliary,  763 
Patches,  mucous,  678 

opaline,  179 
Pathogenesis,  66,  83 
Pathology,  55 

comparative,  57 

general,  55,  58 

of  blood,  405 

special,  58,  385 
Paths  of  infection  of  bacillus  tubercu- 
losis, 148 
Pearl  epithelioma,  326 
Pediculus  capitis,  213 

corporis  humanus,  213 

inguinalis,  213 

ordinarius,  213 

pubis,  213 

vestimenti,  213 
Pemphigus  esophageal,  691 
Pentastoma  denticulatum,  212 
Periadenitis  chronica,  444 
Periappendicitis,  722 
Periarteritis,  520 

nodosa,  525 

simplex,  525 
Peribronchitis,  actinomycotic,  578 

chronic  caseous,  578 

chronica,  577 

syphilitic,  578 
Pericardiomediastinitis,  474 
Pericardiomyocarditis,  464 
Pericarditis,  456 

externa,  474 

in  croupous  pneumonia,   606 

interna,  475 

petrificans,  468 

suppurative,  471 
Pericardium,  adhesions  of,  467 

degenerations  of,  456 

infiltrations  of,  456 

inflammations  of,  456 

malformation  of,  455 

postmortem  examination  of,  10 

tendinous  patches  in,  455 
Perichondritis,  572 
Pericholangitis,  764 
Pericholecystitis,  764 
Pericystitis,  670 
Perigastritis,  700,  702 
Perihepatitis,  758 
Perilymphangitis,  538 
Perinephritis,  634 
Perineurium,  833 
Periosteum,  798 

hemorrhage  under,  803 

inflammation  of,  803.  See  Periostitis. 
Periostitis,  803 

acute  simple,  803 

acute  suppurative,  803 

bacteria  in,  804 

albuminosa,  805 

chronic  productive,  805 


INDKX. 


9»3 


Periostitis,  t'il'i"u>.  •>^j4 
hcinorrhayic,  S04 
ossifying.  S04 
Periostoses.  800 
Perirenal  fat,  atrophy  of,  634 
Perisplenitis.  430 
Perithelioma.  350 
Peritonitis.  45(1 

perigastric.  700 
zymotic.  47() 
Peritonsillitis,  f)Si 
Perityphlitis  actinoinycotica.  73-' 
Periureteritis.  058.  ft<io 
Pernicious  anemia.  42 j 
Perodactylism,  62 
Persistence  of  thymus  gland.  450 
Pestilentia.  128 
Petechise,  264 
Petri  dish  plates.  Q07 
Petrifaction.  237 
Petrunkevitch's  solution.  34 
PfeitTer's  phenomenon,  104 
Phagocytes,  q8 
Phagocytosis,  98.  290 
Phagolvsis.  99 

Pharyngeal  catarrh,  chronic,   bS2 
Pharyngitis.  550.  682 

acute  catarrhal,  68 2 
chronic,  682 
hyperplastic,  683 
hypertrophic,  683 
phlegmonous,  683 
pseudomembranous,  OS 3 
sicca,  683 
Pharvngoceles.  693 

Pharvngomycosis  leptothrica.    170.  683 
Pharvnx,  inflammation  of,  682 
hypertrophy  of,  683 
syphilis  of,  683 
tuberculosis  of,  683 
tumors  of,  685 
Philocytase,  102 
Phlebectasia,  535 

results  of,  536 
Phlebitis.  534 
chronic.  535 
infectious.  534 
non-infective,  534 
recurrent,  534 
suppurative,  534 
Phleboliths.  277 
Phlcb(jsclerosis,  535 
Phlegmon,  woody,  of  neck,  680 
Photogenesis,  85 
Phthirius  inguinalis,  213 

pubis,  213 
Phthisis,  hbroid.  621 
lithogenous,  581 
Nailers.  543 
tuberculous.  614 
Physiology.  55 
morbid,  56 
Pia-arachnoid,  850 

inflammation  of,  850 

secondary  to  myelitis,  881 


Pia-arachnoid,  circulat.-rv  disturbances 
of,  850 
cysts  of,  857 
ehdotheli(Mna  of,  856 
passive  hyperemia  of,  850 
tumors  of,  856 
Pia  mater,  833 

inflammation  "•'    ><:" 
Pigeon-breast,  823 
Pigmentation,  231 
bacterial,  236 

medicamental,  of  mucosa-.  544 
of  carcinoma.  324 
of  sarcoma.  356 
of  suprarenals.  785 
of  tumors.  315 
Pigments,  autochthonous.  231 
blood.  233 

demonstration  of,  236 
external.  232 
extraneous,  231 
hematogenous,  233 
Piles,  736 

Pineal  gland,  diseases  of.  878 
Piroplasma  bioeminum.  70 
Pitfield's   method   of    staining    flagella, 

915  .   . 

Pitres-Nothnagel  method  of  exammmg 

brain.  25 
Pituitary  body,  adenoma  of,  878 
diseases  of,  877 
endothelioma  of,  878 
gummata  of,  877 
tuberculosis  of,  877 
Plague,  128 

bacillus  of,  1 28 
bubonic,  h-mph-nodes  in,  130 
oriental,  128 
pneumonic,  130 
septicemic.  131 
Plasmodium  malaria*.  186 
life  cycle  of,  1 88 
vivax.  189 
Plasmolysis.  410 
Plasmorrhexis,  410 
Plates,  Esmarch's  tube,  007 
Petri  dish.  907 
I   Plating  by  Blake  bottle,  go; 
methods.  906 
Platino-aceto-osmic-acid  mixture,  33 
Platinum  inoculating  needl-^    '>n.>> 
Plethora.  261 

corpuscular.  410 
general.  261 
nvdremic.  261 
lymphatic,  261 
v'ascular,  261 
I  vera.  261 

'    Pleura,    diseases    of.    450.     Sec    Serous 
Mcmbratu^s. 
Pleune,  postmortem  examination  of,  10 
Pleurisy  in  croupous  pneumonia,  605 
putrid,  471 
suppurative,  469 
Pleuritis,  456 


984 


INDEX. 


pneumonia, 


Pleuritis  pctrificans,  468 
Pleurogenous     interstitkil 

61 2- 

Pleuropneumonia,  597 
Pneumo-aspergillosis,  163 
Pneumobacillus,  127 
in  sputum,  948 
Pneumococcus,  109 
Pneumonia,  597 
broncho-,  606 

morbid  histology  of,  609 
termination  of,  610 
catarrhal,  550,  607 
central,  599 
chronic,  604 
chronic  interstitial,  611 
croupous,  597 

abscess  of  frontal  sinus  in,  606 
accompanied  by  endocarditis, 

605 
accompanied  by  pleurisy,  605 
blood-changes  in,   605 
complications  of,  605 
engorgement  in,  600 
gray  hepatization,  603 
meningitis  in,  606 
monarticular   joint    inflamma- 
tion in,  606 
morbid  histology  of,  601 
nephritis  in,  606 
pericarditis  in,  605 
pleurisy  in,  605 
red  hepatization,  600 
sputum  in,  1 1 1,  598 
suppurative  parotitis  in,  606 
terminations  of,  603 
diplococcus  of,  109 
disseminated,  607 
fibrinous,  597 
fibroid,  611 
hypostatic,  583 
interstitial,  611 

termination  of,  614 
lobar,  597 
lobular,  606 

lymphogenous  interstitial,  463 
migratory,  599 
organizing,  604 
plague,  130 

pleurogenous  interstitial,  612 
predisposing  causes  of,  598 
purulent,  597 
septic,  597 
stages  of,  599 
suppurative,  597 
tuberculous,  614 
unresolved,  604 

gray  induration  of,  612 
Pneumonitis,  597 
Pneumonoconiosis,  232,  542 
Pneumopericardium,  479 
Pneumothorax,  479 
Pneumotoxin,  1 1 1 
Poikiloblasts,  409 
Poikilocytes,  408 


Poikilocytosis,  408 
Poisoning,  acute,  75 

chronic,  75 
Poisons,  75 

animal,  75 

as  causes  of  disease,  75 

classified,  77 

corrosive,  75 

elective  action  of,  78 

endogenous  disintegrative,  76 

exogenous,  75 
exotic,  77 

extrinsic,  75 

histogenic,  76 

indigenous,  77 

irritant,  75 

mineral,  75 

neurotic,  75 

parasitic,  77 

vegetable,  75 
Polioencephalitis,  868 

inferior,  868 

superior,  868 
Polioencephalomyelitis,  868,  883 
Poliomyelitis,  788,  881 

acute,  883 

ascending,  883 

anterior,  882 

chronic  anterior,  884 
Polyadenomata  of  stomach,   709 
Polyarthritis,  826 
Polyblast,  302 

Polychrome,  methylene-blue,  48 
Polycythemia,  410 

with     chronic     cyanosis     and     en- 
larged spleen,  411 
Polyetnia,  261 
Polyglobuly,  410 
Polymorphonucleosis,  292 
Polymyositis,  acute,  793 
Polyneuritis,  889 
Polyorrhomenitis,  456 
Polyp,  malignant  placental,  364 

pedunculated,  344 
Polypi,  cardiac,  272 

fibromatous,  272 

fibrous,  of  larynx,  575 

mucous,  of  stomach,  709 

myxomatous,  272 

nasal,  567 

telangiectatic,  567 
Polyserositis,  456 
Pons  varolii,  834 
Porencephalia,  864 
Pork,  measley,  371 
Portal  vein,  thrombosis  of,  741 

zone  of  liver,  737 
Port-wine  marks,  345 
Postmortem  bacteriologic  examination, 
29 
blank,  4 

changes  in  stomach,  695 
chisels,  24 
examinations,  i 
internal  examination  of  bodv,  6 


INDEX. 


985 


Postmortem  examination  of  alxlominal 
cavity,  (j 
of  pericardium.  10 
of  serous  cavities,  454 
of  thoracic  cavity,  q 

external  examination  of  body,  5 

knife.  Virchows,  6 

needles.  30 

preliminary  data  for,  4 

room,  2 

saw,  10 

table,  3 
Postmortems,  technic  of,  i 
Potato  culture-medium,  preparation  of, 
80Q 

culture,  moist  chamber  for,  8qg 

plug  cutter,  000 

sterilization  of,  for  culture-medium, 
8qo 
Pott's  disease,  817,  830 
Precipitins,  104 
Pregnancy,  toxemia  of,  80 
Preparator,  102 
Preservation  of  tissues,  31 

of  urine,  935 
Probes,  ig 
Proctitis.  550.  720 
Production  of  indol.  020 
Products,  bacterial,  85 
Proglottides  of  ccstodes,  1Q4 
Propagation  of  bacteria  by  fission,  82 
Protozoa,  181 
Psammoma,  3 59 

of  brain.  877 
Pseudoarthrosis,  822 
Pseudocirrhosis,  of  liver.  758 
Pseudohermaphrodismus.  63 
P.seudohypertrophic     muscular      paral- 
ysis. 226 
Pseudohypertrophy,  2 1 8 
Pseudoleukemia,  430,  439,  448 

splenica,  430 
Pseudomelanosis,  231,  730 
Pseudomembranous  bronchitis,  577 
Pseudoneuromata.  893 
Pseudopodia,  181 
Pseudo-tuberculosis,  156 
Ptomains,  87.  258 
Ptyalism.  68  7 
Pyelitis,  658 
Pyelonephritis,  641,  643 
Pyemia,  275.  378 

arterial,  510 

streptococcic,  116 
Pygopagus.  92 

Pylorus,  congenital  hypertrophic  steno- 
sis of.  6g6 

obstruction  of,  706 

stenosis  of,  706,  714 
Pyocyanin.  134 
Pyocyanolysin,  134 
Pyofluorescin.  134 
Pyogenic  membrane.  470 
Pyonephrosis,  296,  659 
Pyopericardium,  469,  471 


Pyoperitoneum,  461; 
Pyorrhea  alve»)laris.  678 
Pyo.salpinx,  296.  559 
Pyothor.ix,  469 
Pyo.xanthosc,  134 
Pyrexia,  ^74 

beneficence  of.  380 

paradoxic,  379 
Pulex  canis,  213 

felis,  213 

hominis.  213 

irritans,  213 

minimus  cutem  penetrans,  213 

penetrans,  213 

serraticeps,  213 
Purkinje,  cells  of,  841 
Purpura  rheumatica,  262 
Pus,  294 

in  urine,  937 
Pustule,  malignant,  123 
Putrefaction,  5 

Quartan  parasite,  189 
Quarter  evil,  126 
Quinsy,  681 

Rabies,  860 
Race.  67 
Rachischisis,  842 

partialis,  843 

totalis,  843 
Rachitis,  822 
Rachitismus,  S22 
Ranula.  688 

pancreatic,  367,  774 

retromaxillaris,  688 

sublingualis.  688 

submaxillaris,  688 
Ranvier,  nodes  of,  841 
Ranvier's  microtome,  40 
Rauschbrand,  126 
Raynaud's  disease,  257 
Reaction  of  medium,  (>ii) 
Receptaculum    chyli,    postmortem    ex- 
amination of,  20 
Receptor.  100 

Reeves'  method  of  rapid  infiltration,  38 
Regeneration  of  bone.  814 

of  nerves,  893 
Repair,  300 

and  inflammation,  285 
Repletio,  261 
Reproduction  of  bacteria,  82 

multiplicative,  184 

propagative,  184 
Resorption  of  bone,  800 
Respiration,  organs  of,  564 
Rhabdomyoma,  345 

of  heart,  503 
Rhinitis,  550,  565 

acute  catarrhal,  565 

atrophic,  566 

caseous,  566 

chronic  catarrhal,  ^6^ 


986 


INDEX. 


Rhinitis,  fibrinous,  565 

hypertrophic,  566 

pseudomembranous,  565 

purulent,  566 

scrofulous,  566 

tuberculous,  566 
Rhinoliths,  567 
Rhinorrhea,  568 
Rhinoscleroma,  159 

of  larynx,  572 

of  nasal  mucosa,  566 
Rhizopoda,  181 
Ricin,  252 
Rickets,  822 
Riga's  disease,  67Q 
Rigidity,  cadaveric,  5 
Rigor  mortis,  5 
Rigors,  378 
Rostellum,  195 
Rouleaux,  288 
Rumination,  709 
Rupture,  713 

of  heart, /503 

of  spleen,  439 

spontaneous,  of  esophagus,  693 


Sac  of  hernia,  713 
Saccharomyces  albicans,  166 
cerevisse,  170 
hominis,  171 
Saccharomycetes,  170 
Saccharomycosis,  170 
Sacculation,  congenital,  of  veins,  534 
Safranin,  48 
Salivary  glands,  686 

adenomata  of,  68g 
endotheliomata  of,  689 
hypersecretion  of,  687 
postmortem    examination    of, 

26 
tuberculosis  of,  688 
tumors  of,  689 
Salpingitis,  suppurative,  559 
Salpingo'myelus,  844 
Sand,  biliary,  765 
intestinal,  736 
vesical,  670 
Sapremia,  375 
Saprophytes,  83 
Sarcina?,  106 

Sarcolemma  of  muscle,  788 
Sarcoma,  348 

alveolar,  356 
angiolithic,  359 
chondroid,  361 
clinical  characters  of,  349 
deciduo-cellulare,  364 
diagnostic  features  of,  362 
encephaloid,  353 
fasiculated,  353 
giant-cell,  354 
large  round-cell,  353 
spindle-cell,  354 
latent  malignancy  of,  349 


Sarcoma,  medullary,  353 

melanotic,  356 

mixed-cell,  356,  824 

myeloid,  354 

oat-cell,  353 

of  bladder,  672 

of  brain,  876 

of  esophagus,  693 

of  heart,  503 

of  intestine,  735 

of  kidney,  662 

of  larynx,  575 

of  lymph-nodes,  449 

of  mouth,  686 

of  muscle,  797 

of  nasal  cavity,  567 

of  stomach,  712 

of  suprarenals,  786 

of  thyroid,  783 

osteoid,  361 

round-cell,  353 

secondary  changes  in,  361 

small  spindle-cell,  353 

spindle-cell,  353 

varieties  of,  352 
Sarcomatosis,  350 

cutis,  357 

of  serous  membranes,  487 
Sarcoptes  hominis,  212 
Saw,  double,  26 
Saw-cut,  circumferential,  22 

undertaker's,  21 

wedge-shaped,  23 
Scabies,  212 

Scalds,  changes  produced  by,  70 
Scalpels,  25 
Schistocytes,  408 

Schistosoma  hsematobium,  193,  194 
Schizogony,  184 
Schizomycetes,  106 

division  of,  106 

pathogenic,  106 
Schizont,  184 

Schwann,  white  substance  of,  839 
Scirrhous  carcinoma,  332 
Scissors  for  postmortem,  14 
Sclerosis,  amyotrophic  lateral,  885 

disseminated,    of    nervous    svstem, 
874 

ependymal,  of  brain,  874 

gastric,  702 

granular  ependymal,  of  brain,  874 

insular,  of  brain,  873 
of  spinal  cord,  885 
thyroid,  780 

lobar,  of  brain,  874 

multiple,  of  brain,  873 

of  lung,  612 

of  nervous  system,  835 

of  pancreas,  771 

of  parotid,  686 

of  spinal  cord,  886 

parotid,  686 

posterior  spinal,  886 

primary  lateral,  of  cord,  887 


INDEX. 


c,S7 


Sclerosis,  jnilmonary,  oii 

renal,  653 

smooth  epenclymal,   ol    liraiii.    S74 
Scolecitis.  720 
Scolex,  i()4 
Scoliosis  septi,  564 
Scrofula,  445 
Section  cutting,  35 
Sections,    celloidin,    method   of  mount- 

>"S-  44  ^.     ^ 

method  of  removmg  paranm  from, 

Sediment,  organized,  in  urine,  935 

unorganized,  in  urine,  937 
Segmentation,  myocardial,  403 
Sensitizer,  102 
Sepsis,  cryptogenic,  377 

oral,  678 
Septicemia.  275,  377 

hemorrhagic.  262 

tuberculous,  154 
Septum,  patent,  486 
Sequelae,  66 
Sequestrum.  812.  814 
Serositis,  456 

actinomycotic,  477 

bacteriology  of,  459 

calcifying,  468 

chronic,  472 

serofibrinous  exudative,  473 
serous  exudative,  473 

fibrinous,  461 

multiple,  456 

plastic,  461 

progressive  hyalo-,  473 

serofibrinous,  461 

serous.  461 

suppurative,  469 
Serous  cavities,  air  in,  478 
dropsy  of,  453 
postmortem    ex.iminat  ion     of, 

454 
membranes,  452 

adhesions  of.  467 
carcinomatosis  of,  481 
chronic     hyperplastic     inflam- 
mation of.  473 
chronic  productive   inflamma- 
tion of^,  473 
endothelioma  of,  4S0 
fibrinous  inflammation  of.  461 
hemorrhagic  inflammation  of, 

472 
inflammations  of,  456 
malposition  of.  453 
normal,  452 
primary  tumors  of,  480 
sarcomatosis  of.  481 
structure  of,  452 
tuberculosis  of,  475 
Serum,  human.  898 
monovalent.  116 
polvvalent,  116 
Sewage,    bacteriologic   examiii.itioti    -ji, 
911 


Sex,  relation  of.  to  disease,  66 
Sherringt<jn's  solution,  402 
Sialolithiasis,  687 
Sialorrhea,  68 7 
Sidenjsis,  232,  543 
Simple  adenia.  448 

atrf)phy.  222 
Sinus  thrombosis,  848 
Sinuses,  cerebral,  thrombosis  of,  866 
Situs  inversus,  484 

of  stomach,  695 
viscerum  inversus,  485 
Skin,  carcinf)ma  of,  357 
infection  through.  90 
tuberculosis  of,  156,  703 
warts  of,  317 
vSleeping  sickness,  183 
Smoker's  patch,  679 
SnufHes.  175 

Softening,  central,  of  thrombus.  277 
of  brain,  862 
red.  of  spinal  cord,  887 
yellow,  of  spinal  cord,  882 
white,  of  spinal  cord,  88 1 
Solution,  Bensley's.  34 
Soor,  165 
Soorpilz,  166 
Sore-mouth,  putrid,  075 
Sore-throat,  gangrenous,  557 
Spatula  for  searing  surfaces  of  organs, 

935 
Spermatocele.  367 
Spermatozoa  in  urine.  936 
Sphacelation  en  masse,  255. 
Spider  cells  of  nervous  system.  835 
Spina  bifida,  844.  845 
occulta,  844 
Spinal  cord,  834 

active  hyperemia  of,  879 
anemia  01,  879 
anterior  cornua  of.  879 
anterolateral  columns  of ,  879 
areas  of  sclerosis  in,  880 
ascending  degeneration,  870 
circulatorv     disturbances     of, 

879 
cysts  of,  888 

direct  cerebellar  tract  of,  870 
direct  and  crossed  pyramidal 

tracts  of.  879 
gliomata  of,  888 
gliosarcomata  of,  888 
Gowcrs'  tract.  879 
gray  matter  of.  870 
hemorrhages  into,  880 
heterotopia  in.  S45 
inflammation  of,  880 
insular  scleroses  of.  S85 
lateral  and   posterior  sclerosis 

of.  888 
malformations  of.  84 1 
jwsterolateral  column.  879 
jMjstmortem    examination    of, 

25 
primary  lateral  scleroses  of,  887 


988 


INDEX. 


Spinal  cord,  red  softening  of,  88 1 

secondary     degenerations     of, 
882 
of  posterior  columns, 
879 
tracts  of  Goll  and  Burdach  in, 

878 
tuberculous  lesions  of,  888 
tumors  of,  888 
white  softening  of,  881 
yellow  softening  of,  882 
Spirilla,  106 

Spirillum  choleras  asiaticce,  142,  143 
agglutinins  of,  143 
extracellular     toxins     of, 

143 

of  Vincent,  173 
Spirochetae,  172 

Obermeieri,  172 

of   relapsing   fever,    demonstration 
of,  172 

pallida,  175 

refringens,  175 

Vincent's,  173 
Splanchnoptosis,  431 
Spleen,  431 

actinomycosis  of,  441 

acute  engorgement  of,  434 

acute  hyperplasia  of,  434 

ague  cake,  434 

atrophy  of,  433 

bifid,  433 

calcareous  infiltration  of 

capsular_  fibrosis,  436 

chronic  infections  of,  440 

circumscribed  capsulitis  of,  436 

corneal  fibroma  of,  436 

cyanotic  induration  of,  432 

cysts  of,  441 

emphysema  of,  431 

engorgement  of,  434 

enlarged,  with  chronic  cyanosis  and 
polycythemia,  411 

fibroid,  435 

gangrene  of,  438 

hemorrhage  in,  436 

hypertrophy  of,  433 

hypoplasia  of,  432 

infarction  of,  437 
in  malaria,  191 

in  situs  inversus,  432 

interstitial  laceration  of,  440 

lamellar  fibroma  of,  436 

lardaceous  disease  of,  434 

leprosy  of,  441 

lobulated,  433 

malformations  of,  432 

malposition  of,  431 

metaclastic  C5^sts  of,  440 

movable,  431 

multiple,  433 

passive  congestion  of,  436 

pigmentary  infiltration  of,  433 

postmortem  changes  in,  431 
examination  of,  15 


434 


Spleen,  primitive  epithelioma  of,  439 
pseudomelanosis  of,  43  i 
rupture  of,  439 
sago,  434 
senile,  433 

spontaneous  rupture  of,  440 
subcapsular  laceration  of,  440 
syphilis  of,  440 
tumors  of,  441 
wandering,  43 1 
Spleens,  accessory,  432 
Splenculi,  432 

Splenitis,  acute  diffuse,  434 
chronic  diffuse,  435 
infectious,  434 
Splenization  of  lung,  588 
Splenomegaly,  438 
primitive,  439 
Splenoptosis,  431 
Spondylitis  deformans,  829 
Sporangium,  163 
Spore,  162 

Neisser's  method  of  staining,  914 
Sporoblast,  184 
Sporocyst,  184 
Sporogeny,  184 
Sporont,  184 
Sporozoites,  185 

Sputum,  Charcot-Leyden  crystals  in,  948 
Curschmann's  spirals  in,  947 
elastic  fibers  in,  947 
epithelium  in,  947 
fibrinous  casts  in,  948 
in  croupous  pneumonia,  iii,  598 
method  of  collecting,  946 
neoplastic  fragments  in,  948 
red  corpuscles  in,  946 
technic  of  examining,  946 
white  blood-corpuscles  in,  946 
Stages  of  pneumonia,  599 
Stagnation  of  regurgitation,  260 
Stain,  differentiation  of,  45 

Gabbet's,  for  Bacillus  tuberculosis, 

146 
Neisser's  differentiating,  for  Bacil- 
lus diphtheriae,   119 
Pappenheim's,  for  Bacillus  tubercu- 
losis, 146 
reactions,  bacterial,  84 
Staining,  45 

bacteria,  911,  913 
jar,  44 

polychrome  methylene-blue,  48 
with  carmin.  45 
with  hematoxj^lon,  46 
Stains  for  mvelin,  838 

Wright's  386 
Staphylococci,  pyogenic,  113 
Staphylococcus  epidermidis  albus,  113 
pyogenes  albus,  113 
aureus,  113 
cereus  albus,  113 

fiavus,  113 
citreus,  113 
Starvation  as  a  cause  of  disease,  68 


INDliX, 


989 


Stasis.  266 

Status  lymphatic-US,  451 
Steatc)ma,  341 

Stenosis,    congenital    hyi)crtr(>]>hic,    of 
pylorus,  tn)h 

intuiTiiinatory,  of  larynx,  574 

laryngeal,  574 

of  bronchi,  57S 

of  conus  artcricjsus,  4S7 

of  esophagus,  tn)  i 

of  intestine,  7 14 

of  larynx,  functional,  574 
organic,  574 

of  pulmonary  artery,  487 

of  pylorus,  706 

of  stomach,  bq6 

preaortic,  of  heart,  515 

subvalvular,  of  heart,  515 
Sterilization,  005 

fractional,  go5 

of  platinum  needle,  qoS 
Sterilizer.  Arnold's  steam,  905 

hot-air,  903 
Sternberg's  anaerobic  culture  tube,  917 
Sternopagus,  63 

Stewart's  cover-glass  forceps,  912 
Stomach,  acquired  malpositions  of,  697 

acute  catarrhal  inflammation,    700 

acute  dilatation  of,  707 

atresia  of,  696 

bacteria  of,  697 

bifid,  6c)6 

calculi  in,  698 

carcinoma  of,  709 

chronic     catarrhal     gastritis     with 
erosions,  700,  701 
dilatation  of,  708 
inflammation  of,  701 

congestion  of,  698 

dilatation  of.  706 

fibroma  of,  712 

foreign  bodies  in,  6<)8 

gangrenous  cancer  of,  709 

hair-balls  in,  698 

hemorrhage  of,  698 

hour-glass,  696 

hyperemia  of,  698 

in  situs  inversus,  695 

leather  bottle,  702 

lipoma  of,  7  I  2 

malformation  oi,  6()5 

mal[)osition  of,  b()>, 

mammillated,  701 

multilocular.  696 

mucous  polypi  of,  709 

myoma  of,  71  2 

normal  structure  of,  695 

occult  hemorrhage  from,  699 

papillomata  of,  jo() 

polyadenomata  of,  709 

postmortem  changes  in,  695 
examination  of,   17 

sarcoma  of,  712 

simple  ulcer  of,  703 

situs  inversus  of,  695 


Stomach,  stenosis  of,  ()<;<) 

striugballs  in,  69K 

structure  of,  695 

syphilis  of,  703 

trifid,  6()6 

tuberculosis  of,  703 

tumors  of,  700 

vertical,  f)<)5 

volvulus  of,  (h)7 
Stomatitis,  550,  675 

aphthous,  676 

fetid,  675 

follicular,  675 

gangrenous,  558,  h-jd 

gonorrheal,  677 

mycotic,  165,  563,  675 

parasitic,  675 

pseudomembranous,  h-;- 

putrid,  675 
.    tuberculous,  O77 

ulcerative,  675 

ulcero-membranous,  173 
Stream,  axial,  288 

circumferential,  2SS 

corpuscular.  288 

parietal,  288 

plasmatic,  288 
Streptococcemia,  116 
Streptococci,  106 
Streptococcus  pyogenes,  114,  ^15 
Streptothricosis,  i  70 

of  esophagus,  69 1 

pulmonary,   170 
Streptothrix  madurae,  169 
Stricture,  hysteric,  of  esophagus,  691 

inorganic,  of  esophagus,  691 

of  esophagus,  69 1 

simple,  of  esophagus,  692 

spasmodic,  of  esophagus,  691 
of  urethra,  672 

syphilitic,  of  larynx,  571 
Stringballs  in  stomach.  dSij 
Strongyloides  intestinalis.  204 
Structure,  normal,  of  heart,  482 

of  bacteria,  81 

of  esophagus,  689 

of  intestine,  712 

of  liver,  737 

of  stomach,  695 

of  voluntary  muscle,  788 
Struma,  780 

intratracheal,  575 

lipomatosa  adrenalis,  786 
Strumitis,  780 

acute  suppurative.  780 
Styrone,  49 
Subinfection,  89 

Sublingvial  gland,  postmortem  examina- 
tion of.  26 

growth  in  infants,  679 
Submaxillary    gland,    postmortem    ex- 
amination of,  26 
Substance,  agglutinabic,  104 

sensibilatrice,  102 
Succus  entericus,  673 


990 


INDEX. 


Suffusion,  bloody,  264 

purulent,  296 
Suggillation,  5,  6,  264,  266 
Sunstroke,  72 
Suppuration,  293 

bronchogenic  of  lung,  593 

diffuse,  296 

of  floor  of  mouth,  679 

hepatic,  749 

of  cellular  tissue,  296 

organisms  of,  294 

paraosteal,  804 

peri-esophageal,  691 

pulmonary,  592 
Suprarenals,  accessory,  784 

adenomata  of,  786 

atrophy  of,  785 

calcareous  infiltration  of,  785 

cancer  of,  786 

cysts  of,  786 

degeneration  of,  785 

ectopic,  784 

hemorrhage  into,  785 

hypertrophy  of,  785 

hypoplastic,  784 

inflammation  of,  786 

lardaceous  disease  of,  785 

malformation  and  malposition  of, 
784 

parenchymatous    degeneration    of, 

78s 

pigmentation  of,  785 

postmortem  examination  of,  16 

sarcoma  of,  786 

supernumerary,  784 

syphilis  of,  786 

tuberculosis  of,  787 

tumors  of,  786 
Surra,  783 

Susceptibility  to  tuberculosis,  148 
Symbiosis,  89 
Symptomatology,  65 
Syncephalus,  63 
Syncytioma,  364 
Syndactylism,  61 
Synophthalmia,  564,  847 
Synovitis,  456,  826 

acute  simple  serous,  826 
Syphilis,  174, 

acquired,  177 

lung  in,  623 
manifestations  of,   177 
of  bone,  819 

congenital,  of  bone,  818 

polylobulated  liver  of,  758 

hereditary,  175 

of  bone,  818 

of  brain,  872 

of  dura  mater,  849 

of  intestine,  731 

of  joints,  832 

of  kidney,  661 

of  larynx,  571 

of  liver,  758 

of  lung,  623 


Syphilis  of  mouth,  678 

of  mucous  membranes,  562 

of  muscle,  796 

of  nasal  mucosa,  566 

of  nervous  system,  871 

of  pancreas,  773 

of  pharynx,  683 

of  spleen,  440 

of  stomach,  703 

of  suprarenals,  786 

of  the  myocardium,  502 

of  thyroid,  780 

of  vascular  system,  529 

of  veins,  535 

tertiary,   178 
Syphilomata,  179 
Syringe,  Koch's,  925 
Syringomyelia,  888 

System,     genito-urinary,     infection 
through,  92 


Tabes,  886 

Taenia  echinococcus,  198 

fiavapunctata,  198 

lata,  201 

mediocanellata,  195 

nana,  197 

saginata,  195 

solium,  196 

cysticercus,  form  of,  197 
head  of,  197 
Talqvist's  hemoglobin  scale,  397 
Tapeworms,  194 

armed,  196 

beef,  195 

broad,  201 

dog,  198 

pork,  196 

solitary,  196 
Technic,  bacteriologic,  897 

general  laboratory,  897 

of  disinfection,  922 

of  examining  sputum,  946 
Telangiectoma,  345 
Temperature,  maximum,  920 

minimum,  920 

optimum,  920 

subnormal,  373 
Terata,  monosomatous,  62 

polysomatous,  62,  63 
Teratogenesis,  60 
Tertian  parasite,  186 
Test,  Widal's,  930 

Tests,  chemic,  for  amyloid  material,  203 
Test-tubes,  method  of  filling,  904 
Tetanus,  121 

antitoxin  of,  123 
Tetracocci,  106 
Texas  fever,  79 
Thecitis,  456 

suppurative,  470 
Thermogenesis,  374 
Thermolabile  body,  102 
Thermolysis,  374 


INDEX, 


991 


Thennostahilc  body,  102 
Thitmin.  S3S 

Thoma-Zeiss  hemocytometer,  3gy 
Thoracic  cavity,  postmortem  examina- 
tion of,  9 
duct,  ]>ostmortem  examination  of, 
20 
tuberculosis  of,  154 
Thorac(igastroschisis,  62 
Thoracopagus,  63 
Thoracoschisis,  62 
Thrombophlebitis.  534 
Thrombosis,  270 

mesenteric,  710 

of  cerebral  veins  and  sinuses,  866 
of  coronary  arteries,  501 
of  portal  vein,  741 
of  splenic  fever,  438 
Thrombus,  270 
annular.  272 
arterial,  272 
ball,  272 
bland.  272 
canalized,  272 
central  softening  of,  277 
changes  in,  275 
channeled,  272 
decolorization  of,  276 
distal,  272 

fragmentation  of,  276 
gray,  271 
infected,  272 
liquefaction  of,  275 
marasmic,  273 
mural,  271 
obstructing,  271 
organization  of,  276 
parietal,  271 
portal,  272 
primary,  271 
propagated,  271 
proximal,  272 
red,  271 
secondary,  271 
simple,  272 
softening  of,  275 
stratified,  271 
valve.  271 
venous,  272 
white,  271 
Thrush,  165.  563.  675.  691 
Thymus  body,  450 

atrophy  of,  450 
malposition  of.  450 
persistence  of.  450 
postmortem    examination    of, 

10 
tumors  of,  45  i 
Th\Tocele,  780 
Thyroid  gland,  775 

absence  of  isthmus.  776 
adenoma  of,  783 
anemia  of,  776 
atrophy  of.  777 
cancer  of,  783 


Thyroid  gland,   carcinosarcoma  of.   783 
chondroma  of,  783 
congestion  of.  776 
cysts  of,  784 
degeneration  of.  770 
dermoid  cvsts  of.  784 
fibroma  of.  783 
histology  of.  775 
hyjieremia  of,  776 
hypertrophy  of,  779 
infiltration  of.  779 
inflammation  of.  780 
malformation  of.  775 
malposition  of.  775 
metastasis  of,  784 
mixed  tumors  of,  783 
osteoma  of,  783 
papillary  cystadenoma  of,  ySx 
postmortem    examination    of, 

15 
sarcoma  of,  783 
structure  of,  775 
syphilis  of.  780 
tuberculosis  of.  780 
Thyroidismus.  7 S3 
Thyroiditis,  780 

acute  nonsuppurative,  780 
chronic  interstitial,  780 
Tigrolysis,  122,  770.  857.  859 
Tinea  tonsurans.  164 

versicolor.  164 
Tissue,  embryonic,  304 
granulation.  304 
mdifferent.  304 
method  of  blocking.  36 
Tissues,  preser\-ation  of,  31 

reparative,  304 
Toad  head,  845 
Toisson's  solution.  402 
Toluidin-blue,  838 

staining,  40 
Toluylenediamin,  235 
Tongue,  black,  670 
diseases  of,  678 
lymphangiectasis  of,  686 
wooden,  169 
Tongue-tie,  674 
Tonsil,  actinomvcosis  of.  682 
adenoma  of,  685 
tuberculosis  of.  682 
Tonsillitis.  550.  681 
acute.  681 
chronic.  68  r 

interstitial.  682 
lacunar.  68  2 
follicular.  6.S  i 
lacunar.  681 
parenchymatous.  68 1 
suppurative  interstitial.  681 
Tonsils.  681 

chronic  inflammation  of.  682 
Tophi.  230 

Toxemia  of  pregnancy.  So 
Toxip.  extraccli'ular.  87.  07 
intracellular.  97 


992 


INDEX. 


Toxin,  method  of  preparing,  926 

Toxoids,  loi 

Toxophore  group,  loi 

Trachea,    postmortem   examination   of, 

15 

tumors  of,  575 
Tracheitis,  550,  569 
Transformation,    hyaline,    of    pancreas, 

769 
Transposition,    corrected,    of    vascular 
trunks,  486 

of  vascular  trunks,  486 

of  viscera,  484 
Transudates,  269 
Trauma  as  cause  of  disease,  72 

as  cause  of  malposition,  60 
Trichina  spiralis,  204,  205,  370 
Trichinosis,  204 
Trichiurus,  203 
Trichomonas  intestinalis,  182 

vaginalis,  182 
Tricocephalus  dispar,  203 

trichiurus,  204 
Tricophyton  megalosporon,  164 

tonsurans,  164 
Tridermoma,  370 
Trypanosoma  brucei,  183 

equinum,  183 

equiperdum,  183 

evansi,  183 

gambiense,  183 

lewisii.  183 

theileri,  183 
Trypanosomiasis,  183 
Tsetse  fly,  183 
Tubercle  bacilli  in  urine,  937 

bacillus.  Gabbet's  stain  for,  146 
Pappenheim"s  stain  for,  146 

cretaceous,  616 

gray,  151 

"healed-in,"  616 

histologic,  149 

miliary,  149 

painful  subcutaneous,  341 

quiescent,  152,  616 

yellow,  151 
Tubercula  dolorosa,  894 
Tuberculin,  147 
Tuberculoma,  153 

of  larynx,  571 

of  muscle,  796 
Tuberculosis,  144 

acute    disseminated,    of   lung,    151 

anatomic  divisions  of,  152 

avian,  bacillus  of,  147 

axillary  lymphadenoid,  445 

bacillus  of,  144 

caseous,  of  lung,  620 

of  h-mph-node,  154 

cavities  in,  152 

chronic  caseous,  152 
fibroid,  152 
hyperplastic,  153 

of  intestine,  733 
of  bone,  817 


'uberculosis,  chronic,  of  intestine,  732 
of  joints,  831 
ulcerative,  152 

cured,  151 

extension  of,  153 
by  blood,  154 
by  body  fluids,  155 
by  contiguity,  155 
by  the  lymph-stream,  155 

general  miliary,  155 

healed-in,  151 

hematogenous  miliary,  618 

ingestion,  149 

inoculation,  148 

latent,  151 

localized,  152 

lymphogenous,  617 

massive  of  kidney,  660 

miliary,  152 

of  intestine,  732 

morbid  anatomy  of,  149 

of  bladder,  670 

of  bone,  817 

of  bronchi,  578 

of  central  nervous  system,  873 

of  dura  mater,  849 

of  esophagus,  691 

of  gall-bladder,  764 

of  heart,  502 

of  intestine,  732 

of  joints,  830 

of  kidney,  660 

of  larynx,  571 

of  liver,  759 

of  lung,  614 

acute  miliary,  618 
aerogenous  infection,  615 
mocie  of  infection,  615 
morbid    anatomy    of    chronic 

ulcerating,  620 
pneuinatogenous  infection,  615 
secondary  infection    by     pyo- 
genic organisms.  620 

of  meninges,  853 

of  mucous  membranes,  560 

of  muscle,  796 

of  nasal  mucosa,  566 

of  pancreas,  773  ^ 

of  pharynx,  683 

of  pituitary  body,  877 

of  salivary  glands,  688 

of  serous  membranes,  475 

of  skin,  156 

of  spinal  cord,  888 

of  stomach,  703 

of  suprarenals,  786,  787 

of  thoracic  duct,  154 

of  thyroid  gland,  780 

of  tonsil,  682 

of  veins.  535 

paraosteal,  817 

pulmonary,  614 

mixed  forms  of,  622 

prenatal,  148 

secondary  infection  in,  153 


INDEX. 


>)(>s 


Tuberculosis,  susriptiliility  tu,  14.S 

\    ulcerative  of  intestine,  73J 
Tubcii,  nu'thoil  of  inoculating,  uoS 
Tumor,  acute  splenic,  434 
albus.  Si  7 
chrDuii-  splenic,  4^^ 
nbWkcelUilar,  342  "  " 
fib]r5t)lastic.  353 
yluoV^.^ii 
melanotic,  234 
riniu>rs,  308 

adult  c<Jhnective-tissue.  337 

amyloid,  ^230 

beniyn,  315 

classification  of,  315 

connective-tissue,  337 

embryonic  connective-tissue,  348 

embryonic  epithelial,  322 

epithelial,  31O 

erectile.  346 

extension  by  dissemination,  313 

by  interstitial  growth.  313 
general  considerations  of,  308 
granulation.  170 
growth  V)y  dissemination,  313 

by  infiltration,  313 

bv  local  dissemination,  313 

by  metastasis,  314 
malignant,  315 
metastasis  of,  314 

V)y  the  blood,  314 
mixed.  363  '^^  V  . 

of  thyroid,  7S3      -  \ 
of  bile-ducts,  766  *^ 

of  bladder.  671  •    ^^ 

of  bK)od-vessels,  536 
of  bone,  823 
of  brain.  875 
of  bronchi,  580 

of  dura  mater,  840  % 

oE- esophagus,  630 
ot -.gall-bladder,  766 
of  heart,  303 
of  intestine,  734 
of  kidney,  661 
of  larynx.  574 
of  liver,  761 
'  of luhg,  624 

of  lymph-nodes,  440 
of  mouth,  68 5 
of  mucous  membranes,  563 
of  muscle,  707 
of  nasal  mucosa,  566 
of  nerves,  893 
of  ])ancreas,  773 
of  pharynx,  685 
of  pia-arachnoid.  S56 
of  saliv.iry  glands.  (>8o 
of  spinal  cord.' 888 
of  spleen.  44  i 
of  stomach.  709 
of  suprarenals.  786 
Kt  thymus  body.  451 
of  thyroid  gland.  783 
of  trache.i,  57s 
64 


Tmnors.  parane])hric,  6(13 
pigmentation  of,  315 
l>rimarv,    of     serous     meml^rancs, 

4S0 
sacral,  363 

signs  of  malignancy  in,  350 
transcutaneous,  auto-inoculation  of, 

.^ '  4 
Typhilitis,  720 
Typhoid  fever,  Widal's  test   for.  n  ;  i 


Ulcer,  i^aslric,   703 

coniplications  of,  705 
morbid  anatomy  of.  704 
phagedenic,  29ft 
rodent,  329 

simple,  of  stomach.  703 
tuberculous,  of  intestine.  733 
typhoid,  728 

of  larynx,  570 
Ulceration,  296 
peptic,  703 
Uncinaria  americana,  205 

duodenale.  205 
Uncinariasis,  205 

Unna's  glycerin  ether  mixture,  40 
Urachus,  cyst  of,  633 
Uratemia.  407 

Urea,  production  by  liver,  73S 
Uremia,  407 

Ureter,  malformations  of,  633 
Ureteritis,  550,  659 

cystic,  660 
Urethra,  malformations  of,  633 
spasmodic  stricture  of,  672 
Urethritis.  350.  672 

acute  catarrhal,  672 
posterior,  672 
simple,  672 
I'rine.  acid,  sediment  from,  037 
alkaline,  sediment  from.  937. 
casts  in,  639 
changes  in  acute  nephritis.  O48 

m    chronic    dinuse    nephritis, 

652 
in  chronic  interstitial  nephritis, 

656 
in  lardaccous  disease  of  the  kid- 
ney, 657 
(Xolltction  of  sanii>le  of.  934 
Oistoma  hematoi.ium  in,  194,  937 
•  pithelKyn  in,  <;3; 
Filaria  .^nguinis  hominis  in,  (^3  7 
•.^'-^nT^cornis  in.  037 

imination  of,  934 
;ungi  in,  936 
in.  nt  in,  035 
'  .    fungi  in.  0^7 


Urinoiun^ 


'  in.  0^7 


994 


IXDEX. 


Vaccination,  antityphoid,  141 
X'acuolization.  cellular,  245 

of  muscle-tibers,  701 
Vaginitis  mycotica,  165 
\'alentine's  knife,  ^;^ 
Valvulitis,  505 

arteriosclerotic,  512 
Van  Gieson's  solution,  47 
Varicose  veins.  535 
Varicosit3^  535 

of  esophageal  \'eins,  6go 
A'arix,  535 

chylous.  347 

congenital,  534 

lacteal,  347 
Vascular  system,  48  2 

syphilis  of,  529 
Vegetations,  changes  in,  in  acute  simple 
endocarditis,  509 

production  of,  in  acute  simple  en- 
docarditis, 508 
Vein  stones,  277 
Veins,  ampullary  dilatation  of,  536 

cerebral,  thrombosis  of,  866 

congenital  sacculation  of,  534 

cystic  dilatation  of,  534 

esophageal,  varicosity  of,  690 

inflammation  of,  534 

normal  structure  of,  533 

portal,  thrombosis  of.  741 

splenic,  thrombosis  of,  43S 

syphilis  of,  535 

tuberculosis  of,  535 

varicose.  535 

dilatation  of,  536 
esophageal,  690 
forms  of,  535 
Vermes,  192 

Verruca  necrogenica,  148 
Vesicles  of  brain,  842 
Vibrion  septique,  136 
Vincent,  angina  of,  174 
Virchow's  postmortem  knife.  6 
Viscera,  abdominal,  postmortem  exami- 
nation of.  15 
Visceroptosis,  59.  431 
Volume  index  of  blood-cell,  404 
Volvulus  of  intestine,  712 

of  stomach,  697 
Von  Fleischl's  hemoglobinometer.  390 


Wall  of  abscess,  295 
Wallcrian  degeneration,  86 1 
Warts,  intracystic.  317 
skin.  317' 
villous,  317 
Water,     bacteriologic    examination    of. 
909 
centrifuge,  935 
Weigert's    method    for    demonstrating 
bacteria  in  tissue,  914 
of  staining  nerve  tissue,  839 
Wens,  367 

Wertheim's  medium,  898 
Whipworm,  203 
White  swelling.  817 

Widal's  test,  method  of  conducting.  929 
for  typhoid  fever,  macroscopic 

method.  931 
for  typhoid  fever,  microscopic 

method.  929 
positive  reaction  of,  930 
pseudo-reaction  of,  931 
Wirsung's  duct  of  pancreas,  767 
Wood-tick,  213 
Worm,  guinea,  210 
pin,  203 
thread,  203 
Wright's  coagulometer,  405 

method   for   anaerolDic    cultivation 

in  liquid  media,  918 
stain,  386 


Xerostoma,  687 
X-rav,  changes  induced  bv,  7: 
Xylolbacilline,  88 
Xyphopagus,  63 


Yeast  cells  from  pure  culture,   i  7  i 
fungi,  162 


Zenker's  solution.  35 
Ziehl's  carbol-fuchsin.  40 
Zone,  hepatic  artery,  of  liver, 
hepatic  vein,  of  liver,  737 
Zooid,  195 
Zygote.  184 
Zvmogens,  8x 


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